Circuitos Limbico-Talamico

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Neurosci Biobehav Rev. Author manuscript; available in PMC 2016 August 08.
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Neurosci Biobehav Rev. 2015 July ; 54: 89–107. doi:10.1016/j.neubiorev.2015.01.014.
LIMBIC CIRCUITRY OF THE MIDLINE THALAMUS

Robert P. Vertes1, Stephanie B. Linley1, and Walter B. Hoover2
1Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, FL
33431
2Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458
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Abstract
The thalamus was subdivided into three major groups: sensorimotor nuclei (or principal/relay
nuclei), limbic nuclei and nuclei bridging these two domains. Limbic nuclei of thalamus (or
‘limbic thalamus’) consist of the anterior nuclei, midline nuclei, medial division of the
mediodorsal nucleus (MDm) and central medial nucleus (CM) of the intralaminar complex. The
midline nuclei include the paraventricular (PV) and paratenial (PT) nuclei, dorsally, and the
reuniens (RE) and rhomboid (RH) nuclei, ventrally. The ‘limbic’ thalamic nuclei predominantly
connect with limbic-related structures and serve a direct role in limbic–associated functions.
Regarding the midline nuclei, RE/RH mainly target limbic cortical structures, particularly the
hippocampus and the medial prefrontal cortex. Accordingly, RE/RH participate in functions
involving interactions of the HF and mPFC. By contrast, PV/PT mainly project to limbic
subcortical structures, particularly the amygdala and nucleus accumbens, and hence are critically
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involved in affective behaviors such as stress/anxiety, feeding behavior, and drug seeking
activities. The anatomical/functional characteristics of MDm and CM are very similar to those of
the midline nuclei and hence the collection of nuclei extending dorsoventrally along the midline/
paramidline of the thalamus constitute the core of the ‘limbic thalamus’.
Keywords
nucleus reuniens; rhomboid nucleus; paratenial nucleus; paraventricular nucleus; mediodorsal
nucleus; central medial nucleus; learning and memory; cognition; affect; stress/anxiety; feeding
behavior; drug seeking activity
1. Introduction
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Until recently, the role of the thalamus in complex, limbic-associated, functions has received
relatively little attention. This stems from the rather entrenched view that the thalamus
mainly serves to transfer sensorimotor information to the cortex – and the corollary that once
Address for correspondence: Dr. Robert P. Vertes, Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca
Raton, FL 33431, phone: 561-297-2362, fax: 561-297-2363, vertes@ccs.fau.edu.
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Vertes et al. Page 2
information reaches the cortex the function of the thalamus is essentially complete. The
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cortex then uses this information for important processes that are almost entirely controlled
by the cortex. In effect, a corticocentric view of brain function.
Despite the fact that corticothalamic projections significantly outnumber thalamocortical

projections, the thalamus is generally seen as a gateway to the cortex, and at best, return
corticothalamic projections are thought to modulate signals conveyed from the thalamus to
the cortex. As will be described herein, this view of the thalamus is gradually changing with
the demonstration that the thalamus does not merely route information to the cortex, but
rather integrates signals reaching it from various sources. Depending on the nature of the
information, the thalamus directs it to select subsets of cortical and subcortical structures for
appropriate actions. Accordingly, discrete thalamic lesions alter a host of physiological,
affective and cognitive functions (see below).
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Classically, the thalamus has been described as consisting of specific and non-specific
nuclei, with the specific nuclei mainly responsible for relaying modality-specific
information to the cortex and the ‘non-specific’ nuclei exerting ‘modulatory’ effects on
cortical targets. While this scheme has been revised over the years, it is tempting to
speculate that it essentially evolved from an incomplete knowledge of the thalamus and its
functions. While it was recognized early on that the thalamus was critical for the transfer of
sensorimotor information to the cortex, comparatively little attention was paid to relatively
vast ‘non-relay’ regions of the thalamus, which were characterized as ‘non- specific’. This
would include the anterior nuclei (anterodorsal, anteroventral and anteromedial), lateral
nuclei (lateral dorsal and lateral posterior), mediodorsal nucleus, submedial nucleus,
intralaminar nuclei (central lateral, paracentral, central medial and parafascicular) and the
midline nuclei (paratenial, paraventricular, rhomboid and reuniens). Although some of these
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cell groups were designated as ‘non-specific’ based on their (presumed) widespread

projections to, and global effects on, the cortex, the designation of ‘non-specific’ probably
more resulted from the fact that no specific function(s) could be attributed to them.
Presently, we will (1) describe an alternative classification for nuclei of the thalamus; (2)
define the ‘limbic thalamus’ and its main anatomical/functional features; and (3) discuss, in
depth, the circuitry and functions of the midline thalamus -- as an integral part of the limbic
thalamus. The latter will not only include the midline nuclei, per se, but thalamic groups
lying on or near the midline that share properties with the midline nuclei, primarily, the
central medial nucleus and the medial part of the mediodorsal nucleus. The report generally
deals with the rodent thalamus.
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2. An alternative classification for nuclei of the thalamus

Aside from the general distinction between specific/non-specific nuclei of thalamus,
traditionally, the thalamus has been divided into three anatomical/functional groups: the
principal (or relay) nuclei, the association nuclei, and the midline and intralaminar nuclei
(Price, 1995; Groenewegen and Witter, 2004). The principal ‘or relay’ nuclei receive specific
sensory or motor information via ascending pathways and transmit it to discrete layers and
regions of the cortex. The relay nuclei would include: the lateral geniculate complex (LGN),
medial geniculate nucleus (MGN), ventral posteromedial (VPM) and posterolateral (VPL)
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nuclei, posterior nucleus (PO), ventral lateral nucleus (VL), ventral anterior nucleus (VA)
and ventral medial nucleus (VM).
The “association” nuclei are a largely ill-defined group that differ from the principal nuclei
in that they do not receive direct sensory (e.g., from the retina) or motor information and
essentially do not project to primary sensorimotor cortices. The association nuclei receive
major input from layer 5 pyramidal cells of the sensorimotor cortex and relay this
information to associational areas of cortex – hence association nuclei of thalamus. The
association thalamic nuclei include the mediodorsal nucleus (MD), the anterior nuclei, the
submedial nucleus (SMT), and the lateral nuclei (Groenewegen and Witter, 2004).
The midline and intralaminar thalamic nuclei form a separate group primarily based on: (1)
their distinct location along the midline and within the internal medullary lamina; (2) their
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rather prominent distribution to both subcortical and cortical structures; and (3) their
involvement in processes of arousal and attention. The intralaminar nuclei consist of the
CM, paracentral (PC), central lateral (CL), parafascicular (PF) and subparafascicular (SPF)
nuclei, while the midline nuclei include the paratenial (PT), paraventricular (PV), rhomboid
(RH) and reuniens (RE) nuclei – and in some classifications the intermediodorsal (IMD)
nucleus (Groenewegen and Witter, 2004). The reticular nucleus of thalamus (RT) comprises
a separate group in that it serves as an interface between thalamic nuclei and the cortex and
lacks cortical projections.
A proposed alternative classification would group thalamic nuclei along a continuum from
sensorimotor to limbic nuclei (Vertes et al., 2014). Similar to the classic system, this
classification would consist of three sets of thalamic nuclei: sensorimotor nuclei of
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thalamus, ‘limbic’ nuclei of thalamus and thalamic nuclei bridging these two domains.
While the connections and functions of these three groups would partly overlap (as with the
classical divisions), the sensorimotor group would mainly consist of the principal thalamic
nuclei; the ‘limbic group’ would include the anterior nuclei, MDm, CM and the midline
nuclei (PT, PV, RH and RE), and the sensorimotor/limbic ‘bridging nuclei’ might include the
submedial nucleus, PC, CL, and PF of the intralaminar complex, central and lateral parts of
MD, and the laterodorsal (LD) and lateral posterior (LP) nuclei of the lateral thalamus. This
organization will be further discussed below with an emphasis on the ‘limbic thalamus’.
3. The limbic thalamus

3.1 General considerations
As well documented, the collection of structures currently referred to as the ‘limbic system’
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developed from the early description of Paul Broca of archi/paleo-cortical structures lying
between diencephalon and the neocortex which he designated the limbic lobe. It mainly
consisted of the cingulate gyrus, the parahippocampal gyrus and the hippocampal formation
(HF). Even initially, the limbic lobe was thought to play a prominent role in affective
behavior. The limbic lobe has steadily expanded to include several additional structures
including the amygdala, septum, bed nucleus of the stria terminalis (BST), nucleus
accumbens (ACC) and adjacent regions of the basal forebrain, the hypothalamus and parts of
the brainstem, as well as the ‘limbic cortex’ and the ‘limbic thalamus’. As a whole, these
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structures constitute the generally accepted view of the “limbic system”. Although many of
these (limbic) structures are interconnected by major fiber bundles (e.g., fornix, stria
medullaris, stria terminalis, mammillothalamic tract), the feature which probably most unites
them (into a system) is their presumed shared functional role(s) -- in affective and cognitive
behaviors. If, as suggested, the limbic system is more a functional than anatomical entity,
there are understandably differing views of the structures comprising the system, and
importantly as we learn more about the brain, the limbic system will undoubtedly continue
to expand. This might be particularly true for the limbic thalamus.
In the present re-classification of nuclei of the thalamus, nuclei were characterized as: (1)
sensorimotor, (2) limbic or (3) a combination of both, thus bridging these two domains. As
indicated, this classification represents a continuum (from sensorimotor to limbic):
essentially what distinguishes sensorimotor from limbic regions of thalamus is relative
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degree of involvement in sensorimotor or limbic functions. Specifically, while it is

undeniably the case that sensory and motor regions of the thalamus serve to relay signals
associated sensations/movements to the cortex, this is by no means their sole role. Often
overlooked is the fact that the principal nuclei of thalamus have significant ties to (strictly)
non-sensorimotor regions of the brain and participate in a range of functions – only a subset
of which are sensorimotor.
For example, the LGN of rats consists of three divisions, the dorsal (DLG) and ventral
(VLG) lateral geniculate nuclei and the intergeniculate leaflet (IGL). Whereas the DLG
relays visual information from the retina to the visual cortex, the DLG also receives
‘modulatory’ inputs from several extra-retinal sites including the visual cortex, RT, superior
colliculus (SC), pretectal nuclei and brainstem cholinergic and monoaminergic nuclei
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(Groenewegen and Witter, 2004; Vertes et al., 2014). Along the same lines, but to a much
greater degree, the VLG and IGL are extensively interconnected with non-visual structures,
suggesting a role(s) well beyond an interface between the retina and visual cortex.
The VLG is divided into a medial parvocellular and a lateral magnocellular part with
differing inputs and outputs. The magnocellular VLG receives retinal input but the
parvocellular division does not. Instead the parvocellular VLG receives a diverse array of
afferents from visual structures (e.g., superior colliculus) as well as from several non-visual
sites, mainly of the brainstem, including the periaqueductal gray (PAG), reticular formation
(RF), parabrachial nucleus (PB), raphe nuclei and the locus coeruleus (LC) (Kolmac and
Mitrofanis, 1997; Vertes et al. 2010). Unlike the DLG, the magnocellular and parvocellular
divisions of VLG do not project to the visual cortex but rather distribute to other nuclei of
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the thalamus, to the hypothalamus, and to several brainstem structures (Vertes et al. 2014).
In a comparable manner, the IGL receives retinal and non-retinal inputs, lacks visual cortical
projections, and distributes widely throughout the diencephalon and brainstem and
prominently to the suprachiasmatic nucleus (SCN).
In a sense, then, it may be a misnomer, even to characterize the lateral geniculate complex as
a ‘relay’ nucleus for only the DLG carries visual information from the retina to the visual
cortex. Seemingly, the VGL and IGL, which lack projections to the visual cortex, are not
directly involved in the processing of visual information (visual discrimination), but rather
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mediate the effects of visual stimulation on a host of visual (e.g., visuomotor) and non-visual
(e.g., circadian rhythms) processes. However, despite these caveats, it is certainly the case
that the LGN is indispensable for the transfer of retinal signals to the visual cortex -- and
hence is a thalamic ‘relay’ nucleus. In an analogous manner, but at the opposite end of the
spectrum, a subset of thalamic nuclei predominantly serve ‘limbic-related’ functions and
hence constitute the ‘limbic thalamus’.
In the following, then, we discuss the anatomical and functional properties of midline nuclei
of the thalamus as well as associated nuclei lying medially in the thalamus, as core
components of the limbic thalamus (Fig. 1)
3.2 Nucleus reuniens

The nucleus reuniens (RE), the largest of the midline nuclei, is located in the anterior two-
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thirds of the thalamus. Rostrally, RE is divided into left and right halves, while further
caudally the two sides fuse to become a mass of cells on the midline of the thalamus, lying
immediately dorsal to the third ventricle. The RE is the most thoroughly investigated of the
midline nuclei likely owing to the early demonstration of Herkenham (1978) that RE is the
major source of thalamic input to the hippocampus. Confirming this, several subsequent
studies have demonstrated that RE distributes massively to the hippocampus and in a highly
organized manner (Ohtake and Yamada, 1989; Su and Bentivoglio, 1990; Wouterlood et al.,
1990; Wouterlood, 1991; Dolleman-Van der Weel and Witter, 1996; Risold et al., 1997;
Bokor et al., 2002; Van der Werf et al., 2002; Vertes, 2006; Vertes et al., 2006, 2007; Hoover
and Vertes, 2007, 2012; Cavdar et al. 2008; Cassel et al., 2013; Varela et al., 2014).
Specifically, RE fibers innervating the HF terminate selectively in the stratum lacunosum-
moleculare (slm) of CA1 of the dorsal and ventral hippocampus as well as the molecular
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layer of the dorsal and ventral subiculum and the parasubiculum (Wouterlood et al., 1990;
Vertes et al., 2006). This pattern of projection is illustrated in Figure 2. RE axons form
asymmetric (excitatory) contacts predominantly on distal dendrites of pyramidal cells in slm
of CA1 and the subiculum (Wouterlood et al., 1990). There is an absence of RE projections
to CA2 and CA3 and to the dentate gyrus (DG) of the hippocampus.
In addition to the hippocampus, RE is a rich source of projections to several cortical sites

that collectively would be characterized as ‘limbic’ cortices (Berendse and Groenewegen,
1991; Wouterlood, 1991; Dolleman-Van der Weel and Witter, 1996; Van der Werf et al.,
2002; Vertes et al., 2006, 2007; Hoover and Vertes, 2007, 2012; Cassel et al., 2013; Varela et
al., 2014). They include the medial (MO) and ventral orbital (VO) cortices, the infralimbic
(IL), prelimbic (PL) and anterior cingulate (AC) cortices of the medial prefrontal cortex
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(mPFC), the dorsal (AId) and ventral agranular insular cortices, rostral retrosplenial cortex,
perirhinal cortex, and the medial and lateral entorhinal cortices. Figure 3 shows pronounced
RE projections to the mPFC, most heavily concentrated in layers 1 and 5/6 of IL and PL of
the ventral mPFC. The subcortical projections of RE are limited and mainly directed to the
claustrum and to the anterior pole of ACC.
Two very prominent targets of RE are the hippocampus and the mPFC (Vertes et al., 2006;
Hoover and Vertes, 2012; Varela et al., 2014). Recent reports, using retrograde fluorescent
techniques, have described collateral RE projections to these two structures (Hoover and
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Vertes, 2012; Varela et al., 2014). For instance, Hoover and Vertes (2012) demonstrated that,
depending on specific sites of paired injections in the two sites, approximately 3-9% of RE
cells projected, via collaterals, to the HF and mPFC. Although such cells (collateralizing)
were rather dispersed throughout RE, they were most numerous in the lateral one-third of
RE, just medial to the lateral wings of RE. It was further shown that, while intermingled, RE
neurons projecting to one structure or the other (non-branching) were preferentially
localized to distinct subregions of RE; that is, cells projecting to the mPFC were
concentrated in the lateral wings of RE (or perireuniens nucleus), while those distributing to
the hippocampus were most numerous in the rostral pole of RE. Finally, an approximately
10-fold greater number of RE cells projected to the ventral than to the dorsal hippocampus
(Hoover and Vertes, 2012).
In accord with the foregoing, Varela et al. (2014) reported that on average 8% of RE cells,
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spanning its rostrocaudal axis, gave rise to collateral projections to the hippocampus and to
the ventral mPFC. Interestingly, they further showed that only about 1% of hippocampal
neurons (of the subiculum) projected dually (via collaterals) to RE and to the mPFC. It was
suggested that RE cells with branching projections to the hippocampus and to the mPFC
may play a critical role in systems consolidation of memory or in the synchronization of the
theta rhythm during exploratory behaviors (Varela et al., 2014).
Whereas the output of RE is ‘relatively’ restricted to the hippocampus and limbic cortices
(mainly the orbitomedial and parahippocampal cortices), reuniens receives a vast and diverse
array of afferent projections from the cortex, hippocampus, basal forebrain, amygdala,
hypothalamus and brainstem (Herkenham, 1978; Sesack et al., 1989; Witter et al., 1990;
Wouterlood et al., 1990; Cullinan and Zaborszky, 1991; Hurley et al., 1991; Canteras and
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Swanson, 1992; Vertes, 1991, 1992; Risold et al., 1994, 1997; Canteras et al., 1995; Vertes et
al., 1995; Naber and Witter, 1998; Canteras and Goto, 1999; Moore et al., 2000; Krout et al.,
2002; Vertes, 2002, 2004; Jasmin et al., 2004; McKenna and Vertes, 2004; Hoover and
Vertes, 2011).
Specifically, using retrograde tracers, McKenna and Vertes (2004) showed that RE receives
widespread projections from subcortical and cortical sites. The main sources of afferents to
RE were from the orbitomedial, insular, ectorhinal, perirhinal and retrosplenial cortices; the
subiculum of hippocampus; the claustrum, lateral septum (LS), BST, and medial, lateral and
magnocellular preoptic nuclei of the basal forebrain; the lateral habenula (LH),
paraventricular and lateral geniculate nuclei of the thalamus; the zona incerta (ZI); the
anterior, ventromedial, lateral, perifornical, posterior, supramammillary (SUM) and dorsal
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premammillary nuclei of the hypothalamus; and the ventral tegmental area (VTA), PAG,
precommissural nucleus, parabrachial nuclei, laterodorsal tegmental nucleus (DR) (LDT)
and the dorsal and median raphe (MR) nuclei of the brainstem.
As described, RE prominently targets the hippocampus and mPFC and return projections are
very pronounced indicating strong reciprocal RE connections with the HF and the mPFC.
Regarding the hippocampus, retrograde tracer injections in RE were shown to produce
marked cell labeling within the ventral subiculum of the hippocampus (McKenna and Vertes,
2004). As depicted in Figure 4, a Fluorogold injection in RE gave rise to a dense band of

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labeled cells dorsoventrally throughout the ventral subiculum of hippocampus. With respect
to the mPFC, anterograde injections in the ventral mPFC produced substantial terminal
labeling throughout the extent of the midline thalamus, with an absence of labeling in non-
midline, or lateral, regions of the thalamus (Vertes, 2002). As shown in Figure 5, labeling
was particularly strong rostrocaudally throughout the medial division of the mediodorsal
nucleus (MDm) and within nucleus reuniens.
While it is well recognized that the hippocampus heavily targets the mPFC (Swanson, 1981,
Ferino et al., 1987; Jay and Witter, 1991; Carr and Sesack, 1996; Hoover and Vertes, 2007),
interestingly there are no return projections from the mPFC to the hippocampus (Laroche et
al., 2000; Vertes, 2004). The demonstration, however, of strong projections from the mPFC
to RE, and, in turn, from RE to the hippocampus (Vertes, 2002; Vertes et al., 2006) suggests
that RE may be the principal route for the transfer of information from the mPFC to the
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hippocampus -- thus completing an important functional loop between these structures.

Supporting this, at the ultrastructural level, mPFC fibers distributing to the RE have been
shown to form asymmetric (excitatory) contacts on proximal dendrites of RE cells projecting
to the hippocampus (Fig. 6) (Vertes et al., 2007).
Consistent with pronounced RE projections to HF and mPFC, nucleus reuniens has been
shown to exert strong excitatory actions at CA1 of the hippocampus and at the mPFC
(Dolleman-Van der Weel et al., 1997; Bertram and Zhang 1999; Viana Di Prisco and Vertes,
2006). Dolleman-Van der Weel et al. (1997) demonstrated that RE stimulation produced
large negative-going field potentials (sink) at slm of CA1 as well as paired pulse facilitation
at CA1. Bertram and Zhang (1999) compared the effects of RE and CA3 stimulation on
population responses (field EPSPs and spikes) at CA1 and reported that RE actions at CA1
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were equivalent to, and in some cases considerably greater than, those of CA3 at CA1. They
concluded that the RE projection to the hippocampus “allows for the direct and powerful
excitation of the CA1 region”. This thalamo-hippocampal connection bypasses the
trisynaptic/commissural pathway that has been thought to be the exclusive excitatory drive
to CA1” (Bertram and Zhang, 1999). Viana Di Prisco and Vertes (2006) confirmed the
excitatory effects of RE on the hippocampus, and further showed that RE stimulation
produced large monosynaptically-elicited evoked responses dorsoventrally throughout the
mPFC, with most pronounced actions (latency and amplitude) at the ventral mPFC -- or at
PL and IL.
3.3 Rhomboid nucleus

The rhomboid nucleus (RH) is a rather small cell group that lies just dorsal to nucleus
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reuniens and overlaps with approximately the caudal two-thirds of RE. It is quite
recognizable by its rhomboid-like shape, hence its name.
By comparison with RE, relatively few reports have examined the anatomical connections of
RH (Ohtake and Yamada, 1989; Berendse and Groenewegen, 1990, 1991; Van der Werf et
al., 2002; Vertes et al., 2006, Hoover and Vertes, 2007). With notable exceptions (see
below), the inputs and outputs of RH are similar to those of RE. Whereas RE projections are
essentially confined to limbic cortices, RH, however, distributes more widely over the cortex
to limbic and non-limbic regions. The primary cortical targets of RH are the medial orbital,
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the mPFC (AGm, AC, PL, IL), posterior agranular insular, primary and secondary
somatosensory, retrosplenial, posterior parietal, perirhinal, occipital, and temporal cortices,
and the hippocampus. Although present, RH projections to the hippocampus are much less
pronounced than those from RE.
The subcortical projections of RH are also considerably more widespread than those of RE.
Subcortically, RH fibers distribute fairly widely throughout the anterior forebrain to the
claustrum, the dorsal striatum (caudate putamen, C-P), LS, the core and shell of ACC, the
olfactory tubercle (OT), and to the basal nuclei of the amygdala. RH projections to the
striatum are restricted to medial aspects of the caudate-putamen, and are considerably less
dense than those to C-P from the dorsally adjacent central medial nucleus (see below). Two
prominent subcortical targets of RH are the nucleus accumbens (Fig. 7) and the basolateral
nucleus (BLA) of the amygdala.
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Although data is limited, it appears that RH receives a diverse and widespread set of afferent
projections from cortical and subcortical sites (Sesack et al., 1989; Hurley et al., 1991; Krout
et al., 2002; Vertes, 2002, 2004; McKenna and Vertes, 2004; Owens, 2005). With some
overlap, afferents to RH are distinct from those to RE -- with a major difference being that
unlike RE, the rhomboid nucleus receives significant input from non-limbic (sensory/motor)
structures.
Cortical afferents to RH derive from limbic and non-limbic regions of the cortex. While
fibers throughout the medial wall of the PFC (or mPFC) distribute to RH, they arise most
strongly from the dorsally located AGm and taper ventrally in the mPFC. In contrast to other
midline nuclei, RH receives marked input from the primary motor cortex and from the
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primary and secondary somatosensory cortices. Aside from input from parts of the insular
and medial PFC, RH receives limited projections from ‘limbic’ cortices, and notably few
projections from parahippocampal cortices and the hippocampus (Van der Werf et al., 2002;
McKenna and Vertes, 2004; Cassel et al., 2013; Vertes et al., 2014).
In general, subcortical forebrain inputs to RH are not extensive, arising most heavily from
the claustrum, substantia innominata, and ZI, and to a lesser degree from the posterior and
lateral nuclei of the hypothalamus and parts of the amygdala. As with other midline and
intralaminar nuclei (Krout et al., 2002; Van der Werf et al., 2002; Groenewegen and Witter,
2004; McKenna and Vertes, 2004; Cassel et al., 2013; Vertes et al., 2014), the brainstem is a
major source of afferents to RH. Fibers originate from ‘limbic-related’ brainstem sites such
as the VTA, PAG, pedunculopontine tegmental nucleus (PPT), LDT and the parabrachial
complex, but also from ’motor’ nuclei including the substantia nigra-pars reticulata,
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mesencephalic RF, SC, and the anterior pretectal nucleus
3.4 Reuniens and rhomboid nuclei: Functional Considerations

A number of recent reports have described the effects of lesions/inactivation of RE on
behavior, with many studies including RH with RE due to their close proximity and
difficulty in separately evaluating their effects on behavior (Dolleman-van der Weel et al.,
2009; Davoodi et al., 2009, 2011; Eleore et al., 2011; Hembrook and Mair, 2011; Hembrook
et al., 2012; Loureiro et al., 2012; Cholvin et al., 2013; Hallock et al., 2013; Prasad et al.,
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2013). While a consensus has not been reached, it appears that RE (or RE/RH) is critically
involved in behaviors associated with the mPFC or those that depend on interactions
between the hippocampus and mPFC.
In an initial study, Dolleman-van der Weel et al. (2009) reported that rats with excitotoxic
lesions of RE did not significantly differ from controls in the acquisition and retention of a
water maze reference memory task. For instance, on the probe test following acquisition, RE
lesioned rats swam directly to the correct quadrant of the pool. However, interestingly, upon
not finding the platform, these rats immediately adopted a strategy of searching the entire
pool for the platform. The deficit was described as non-mnemonic -- or a reduced ability to
shift strategies. Accordingly, it was viewed as a medial PFC rather than a hippocampal
dysfunction. Subsequent studies have similarly shown that inactivation of RE/RH does not
alter acquisition or retrieval on a standard water maze task (Loureiro et al., 2012; Cholvin et
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al., 2013). In accord with a RE involvement mPFC-associated functions (Dolleman-van der

Weel et al., 2009), Prasad et al. (2013) showed that rats with RE lesions were unable to
inhibit premature responses on a five choice reaction time task -- an impulsive behavioral
pattern characteristic of damage to the prefrontal cortex (Chudasama et al. 2003).
While the foregoing suggests that RE lesions may affect mPFC- but not hippocampal-
dependent tasks, the developing notion is that RE is most directly involved in tasks requiring
the interactions of the HF and mPFC. For instance, Hembrook and Mair (2011) initially
showed that RE/RH lesions significantly altered performance on a delayed non-match to
sample radial arm maze task which is sensitive to damage to the hippocampus or to the
mPFC (McDonald and White, 1993; Porter and Mair, 1997; Mair et al., 1998), but were
without effect on a visuospatial reaction time task sensitive to alterations of the striatum or
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the motor cortex. Hembrook et al. (2012) subsequently examined the effects of reversible
inactivation of RE/RH: (1) on a delayed non-match to position task in an operant chamber
sensitive to lesions of the HF or the mPFC; and (2) on a variable choice radial maze delayed
non-matching task responsive to hippocampal but not to mPFC lesions (Porter et al., 2000).
RE/RH inactivation significantly disrupted performance on the delayed non-match to
position but not on the radial maze task. The authors concluded that “RE and RH affect
measures of spatial working memory that depend on interactions of between the
hippocampus and mPFC, but not measures that depend on the hippocampus alone”
(Hembrook et al., 2012).
Using a different set of tasks, Cassel and colleagues similarly concluded that RE/RH
selectively participate in functions requiring the cooperative actions of the hippocampus and
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the mPFC (Loureiro et al., 2012; Cholvin et al., 2013; Cassel et al., 2013). Specifically,
lesions of RE/RH had no effect on either the acquisition or short term retention (5 days post-
acquisition) of a water maze task, but disrupted long-term retention (25 days) on the task
(Loureiro et al., 2012). As was pointed out, recent memory (5 days) involves the
hippocampus, whereas remote memory (25 days) enlists both the hippocampus and the
mPFC (Clark et al., 2005; Broadbent et al., 2006; Teixeira et al., 2006; Lopez et al., 2012).
In a follow-up report, Cholvin et al. (2013) compared the effects of selective inactivation of
the hippocampus, the mPFC or the RE/RH on a standard water maze task and on a ‘double-
H’ water maze task that places demands on both the hippocampus (place identification) and
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the mPFC (strategy-shifting) for successful completion. Only hippocampal inactivation

impaired performance on the standard water maze task, whereas inactivation of the
hippocampus, mPFC, or the RE/RH disrupted performance, and to a similar degree, on the
double-H water maze task. According to the authors, the hippocampus serves a recognized
role in spatial memory, the mPFC in set shifting, and RE/RH may act “as the coordinator of
this processing” (Cholvin et al., 2013).
Finally, Hallock et al. (2013) compared the effects of RE/RH suppression on two versions of
a conditional discrimination T-maze task: one involving a working memory component and
the other not. RE/RH inactivation severely disrupted performance on the working memory
version but not on the conditional discrimination version of the task, leading the authors to
conclude that RE/RH is a necessary component of working memory performance which is
“thought to depend on the hippocampal-prefrontal circuit.”
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3.5 Paraventricular nucleus

The paraventricular nucleus (PV) is located medially below the third ventricle and
dorsomedial to the mediodorsal nucleus, and essentially spans the rostro-caudal length of the
thalamus. PV distributes fairly widely throughout the forebrain to cortical and subcortical
structures (Berendse and Groenewegen, 1990, 1991; Meredith and Wouterlood, 1990; Su
and Bentivoglio, 1990; Turner and Herkenham, 1991; Brog et al., 1993; Conde et al., 1995;
Moga et al. 1995; Bubser and Deutch, 1998; Otake and Nakamura, 1998; Pinto et al., 2003;
Jasmin et al., 2004; Peng and Bentivoglio, 2004; Parsons et al., 2006, 2007; Hoover and
Vertes, 2007; Shin et al., 2008; Li and Kirouac, 2008; Vertes and Hoover, 2008). The
principal targets of PV are IL and PL of the mPFC, dorsal agranular insular cortex, ventral
subiculum of hippocampus, claustrum, lateral septum, core and shell of ACC, OT, BST,
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medial, central, cortical and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and
dorsomedial nuclei of the hypothalamus (Li and Kirouac, 2008; Vertes and Hoover, 2008).
In addition, the caudal PV distributes to dorsal striatum. Figure 8 shows pronounced
projections from the rostral PV to ACC and BST, while Figure 9 depicts massive caudal PV
projections to the central and basal nuclei of the amygdala at four rostro-caudal levels of the
amygdala.
The PV receives a relatively diverse array of afferents from the forebrain and the brainstem
(Cornwall and Phillipson, 1988; Sesack et al., 1989; Chen and Su, 1990; Hurley et al., 1991;
Vertes, 1991, 1992, 2002; Otake and Nakamura, 1995; Otake et al., 1995; Vertes et al., 1995,
1999; Ruggiero et al., 1998; Novak et al., 2000; Krout et al., 2002; Goto and Swanson, 2004;
Peng and Bentivoglio, 2004; Kirouac et al., 2005, 2006; Otake, 2005; Hoover and Vertes,
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2011; Li and Kirouac, 2012).
A major source of input to PV is from the cortex, or specifically from the mPFC and insular
cortices (Groenewegen, 1988; Sesack et al., 1989; Chen and Su, 1990; Hurley et al., 1991;
Vertes, 2002, 2004; Jasmin et al., 2004; Hoover and Vertes, 2011; Li and Kirouac, 2012).
Whereas fibers throughout the mPFC project to PV, there is a dorsal to ventral gradient in
intensity such that AGm and AC distribute moderately, and PL and IL massively, to PV
(Vertes, 2002, 2004; Li and Kirouac, 2012). Some cortical inputs differentially favor anterior
or posterior parts of PV (Li and Kirouac, 2012); that is, the ventral subiculum projects more
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heavily to the anterior than to the posterior PV, whereas IL, PL and the posterior agranular
insular cortex preferentially distribute to the posterior PV.
The main subcortical afferents to PV arise from structures of the hypothalamus and
brainstem, with additional but more limited input from BST and parts of the amygdala. PV
receives projections from several nuclei of the hypothalamus including the
tuberomammillary, SUM, dorsomedial, posterior, lateral and parasubthalamic nuclei -- as
well as from the medial preoptic area and diagonal band nuclei (Vertes, 1992; Vertes et al.,
1995; Goto and Swanson, 2004; Kirouac et al., 2005, 2006; Menzie et al., 2010; Li and
Kirouac, 2012). In addition, PV is essentially unique among the midline nuclei in that it
receives afferents from the suprachiasmatic nucleus and the intergeniculate leaflet (Moore et
al., 2000; Kawano et al., 2001). While varying in density, brainstem projections to PV derive
from VTA, the pontomesencephalic RF, nucleus cuneiformis, nucleus of Darkschewitsch,
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the dorsal and median raphe nuclei, regions of the PAG, parabrachial nucleus, LDT and PPT,
LC, and the solitary nucleus (Chen and Su, 1990; Takada et al., 1990; Bester et al., 1999;
Krout and Loewy, 2000a, 2000b; Krout et al., 2002; Li and Kirouac, 2012
3.6 Paratenial nucleus

The paratenial nucleus (PT) is a slender, elongated nucleus located in the anterior thalamus.
It borders the paraventricular nucleus laterally and overlaps with approximately the rostral
one-third of PV. Compared to PV, less attention has been paid to the efferent projections of
PT, probably owing to its small size (Berendse and Groenewegen, 1990, 1991; Turner and
Herkenham, 1991; Brog et al., 1993; Conde et al., 1995; Van der Werf et al., 2002; Jasmin et
al., 2004; Hoover and Vertes, 2007; Vertes and Hoover, 2008). Nonetheless, the output of PT
is substantial and largely parallels that of PV (Vertes and Hoover, 2008). The main cortical
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targets of PT are the medial frontal polar, AC, PL, IL, medial orbital, dorsal agranular
insular, piriform and entorhinal cortices, and the ventral subiculum of the hippocampus.
Figure 10 shows dense PT projections to the medial orbital, PL and IL cortices at three
rostrocaudal levels of the mPFC.
Principal subcortical sites of projection of PT are the claustrum, the core and shell of ACC,
the medial sector of C-P, BST, and caudal parts of the central and basal nuclei of the
amygdala. PT also distributes lightly/moderately to the ventral orbital and perirhinal
cortices, the dorsal subiculum, lateral septum, medial and cortical nuclei of amygdala, and
the lateralhypothalamus (Vertes and Hoover, 2008).
As with PT projections, much less is known of inputs to PT than for other midline thalamic
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nuclei including PV. Nonetheless, an understanding of major sources of afferents to PT has

emerged from anterograde studies that traced projections to PT (Cornwall and Phillipson,
1988; Groenewegen, 1988; Sesack et al., 1989; Chen and Su, 1990; Hurley et al., 1991;
Krout et al., 2002; Vertes, 2002, 2004; Jasmin et al., 2004; Hoover and Vertes, 2011). With
some notable exceptions, PT and PV receive similar sets of inputs. PT receives substantial
input from rostral regions of the ‘limbic’ cortex -- or from the medial, orbital, and insular
PFC (Sesack et al., 1989; Hurley et al., 1991; Vertes, 2002, 2004; Jasmin et al., 2004;
Hoover and Vertes, 2011). Specifically, PT receives prominent projections from the ventral
mPFC (IL and PL), from the (rostral) agranular insular cortex and from medial and ventral
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orbital cortices (Jasmin et al., 2004; Hoover and Vertes, 2011). Forebrain subcortical
structures distributing to PT mainly include the ventral subiculum and the claustrum, and to
a lesser degree, LS, diagonal band nuclei, BST, medial nuclei of amygdala, reticular
thalamic nucleus, ZI, and parts of the hypothalamus (Chen and Su, 1990). Like PV,
brainstem afferents to PT originate from DR, MR, PAG, LC, parabrachial nucleus, LDT, and
the solitary nucleus
3.7 Differential projections of the paraventricular and paratenial nuclei

While largely overlapping, there are some notable differences in the projections of PT and
PV. In brief, the output of PT is more strongly weighted to (limbic) cortical than to
subcortical structures, whereas the opposite is true for PV: limbic subcortical greater than
cortical. In particular, PT distributes more widely throughout the cortex, and more intensely
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than PV to the medial orbital cortex, the ventral mPFC, the lateral entorhinal cortex, the
ventral subiculum, and the dorsal striatum. On the other hand, PV fibers terminate more
heavily in BST, the central and basal nuclei of the amygdala and most of the hypothalamus.
Both PT and PV, however, distribute massively to the ACC (Vertes and Hoover, 2008).
3.8 Paraventricular nucleus: Functional considerations

By comparison with RE and RH which target the hippocampus and limbic cortical structures
involved in cognitive functions, the paraventricular nucleus of the dorsal midline thalamus
preferentially distributes to limbic subcortical sites such as the septum, BST, ACC, and the
amygdala. Accordingly, PV has been directly implicated in affective functions such as stress
and anxiety, feeding behavior, and drug seeking activities (for review, Hsu et al., 2014;
Matzeu et al., 2014). Little is known regarding the functions of PT.
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The paraventricular nucleus is activated by wide range of stressors such as fear/anxiety,

immobilization, and footshock-induced stress, and thus appears responsive to stress, per se,
independent of its specific source (Chastrette et al., 1991; Bubser and Deutch, 1999). PV has
been shown to be instrumental in the adaptation to acute stressors following periods of
chronic stress. For example, rats exposed to a repeated (chronic) stressor become habituated
to that stressor, so when the stressor is re-introduced it produces less of a response than to its
initial exposure. However, if a different stressor is introduced after habituation, the response
to it is magnified, possibly signaling the presence of novel, potentially threatening, stimuli.
PV appears to be involved in both processes: that is, adaptation to the original stressor and
the heightened response to a novel stressor (Bhatnagar and Dallman, 1998; Bhatnagar et al.,
2002; Heydendael et al., 2011). Specifically, posterior PV lesions block habituation to
repeated restraint stress (Bhatnagar et al., 2002) and c-fos expression in PV is significantly
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elevated when novel stressors are applied after a chronic stressor (Bhatnagar and Dallman,
1998).
Although more typically responsive to “negative” stimuli, PV cells are also activated by
rewarding conditions and thus may generally encode emotionally salient events (Igelstrom et
al., 2010; Hsu et al., 2014; Matzeu et al., 2014). Specifically, PV has been shown to serve a
role in feeding behavior -- which may be a model system for appetitive functions. For
instance, c-fos levels in PV are enhanced in anticipation of feeding in food-deprived rats,

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and PV lesions attenuate anticipatory locomotor activity associated with feeding (Nakahara
et al. 2004; Angeles-Castellanos et al. 2007). More recently, Choi et al. (2012) demonstrated
that direct injections of orexin-A in PV produced a marked increase in dopamine release in
ACC and elicited hedonic feeding -- an overconsumption of palatable foods. Similar to the
reward circuit for food (Choi et al., 2010, 2012), the core circuitry for drug seeking behavior
reportedly involves orexinergic projections from the lateral hypothalamus to PV and in turn
PV projections to the nucleus accumbens (Martin-Fardon and Boutrel, 2012; Matzeu et al.,
2014). Regarding a role for PV in drug-seeking behavior, lesions or inactivation of PV
suppress drug-seeking activities (Hamlin et al., 2009; James et al. 2010; Marchant et al.,
2010), while cue-induced reinstatement of cocaine seeking behavior strongly correlates with
c-fos activation in PV (James et al., 2011). In addition, injections of orexin-A in PV
reinstated extinguished cocaine and sweetened condensed milk seeking behaviors (Martin-
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Fardon et al., 2011). Finally, there may be a link between a PV involvement in stress/anxiety
and in overeating and drug seeking behavior in that stress tends to exacerbate the latter
behaviors (Martin-Fardon and Boutrel, 2012; James and Dayas, 2013).
3.9 Mediodorsal nucleus, medial division

The mediodorsal nucleus (MD) is a large nucleus situated dorsally and medially in the
thalamus. The two halves of MD are separated by PV and by the intermediodorsal nucleus
(IMD). MD is bordered dorsally by the habenular complex, rostrally by PT, and caudally by
the parafascicular nucleus of the intralaminar thalamus. Hence MD is virtually ‘encircled’
by the midline and intralaminar nuclei of thalamus. The MD in rats is divided into three
segments: medial (MDm), central (MDc) and lateral (MDl) divisions, and generally a fourth
part, lateral to MDl, termed the paralamellar MD (MDpl) -- as it abuts the internal medullary
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lamina (Leonard, 1969, 1972; Krettek and Price, 1977; Groenewegen, 1988).
The different segments of MD are characterized by distinct input-output relationships and

distinct sets of functions. On the whole, MD is strongly reciprocally connected with the
medial, orbital and insular prefrontal cortices, but interestingly is the source of relatively
minor projections to other parts of the cortex (Krettek and Price, 1977; Reep and Winans,
1982; Groenewegen, 1988; Conde et al., 1990; Ray and Price, 1992; Reep and Corwin,
1999; Vertes, 2002, 2004; Jasmin et al., 2004; Gabbott et al., 2005; Rotaru et al., 2005;
Hoover and Vertes, 2007, 2011). In fact, the prefrontal cortex of rodents was initially
designated as a “MD projection cortex” (Leonard, 1969; Uylings and van Eden, 1990). As
with other regions of the PFC, mediodorsal connections with the medial prefrontal cortex are
highly topographically organized, such that medial to lateral segments of MD are mapped
onto ventral to dorsal regions of the mPFC. Specifically, MDm reciprocally connects with
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IL, the lateral part of MDm and MDc with PL and the ventral AC, the MDl with the dorsal
AC, and MDpl with AGm (Groenewegen, 1988; Ray and Price, 1992; Vertes, 2002; Hoover
and Vertes, 2007). Figure 5 shows massive projections from the infralimbic cortex to MDm.
In a similar manner, specific segments of MD connect with distinct regions of the orbital
cortex. MDm is reciprocally linked to the medial orbital (MO) cortex, MDc to the lateral
orbital cortex, MDl to the ventral (VO) and ventrolateral (VLO) orbital cortices, and ventral
aspects of MDc and MDl to the dorsolateral orbital (DLO) cortex (Groenewegen, 1988; Ray
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and Price, 1992; Hoover and Vertes, 2011). insular cortex, MDm interconnects with the
dorsal (AId) and posterior Regarding the agranular insular cortices, and MDc with the
ventral agranular insular cortex (Groenewegen, 1988; Ray and Price, 1992; Jasmin et al.,
2004). With some overlap, the foregoing indicates that MDm, in contrast to lateral parts of
MD, primarily communicates with limbic regions of the PFC. This is consistent with the
functional properties of MDm (see below).
Similar to the interconnections of MD with the PFC, most subcortical structures projecting
to MD target specific segments of MD, but some (mainly of the brainstem) distribute
throughout MD (Young et al., 1984; Groenewegen, 1988; Kuroda and Price, 1991a, 1991b;
Ray and Price, 1992; Vertes, 1991, 1992; Zahm et al., 1996; Morin and Meyer-Berstein,
1999; Vertes et al., 1999; Krout et al., 2002; Tripathi et al., 2012). MD is typically described
as composed of three functional units: motor (MDl/MDpl), olfactory (MDc) and limbic
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(MDm), and with some overlap, subcortical inputs to MD reflect these functional divisions.
For instance, afferents to lateral segments of MD (MDl/MDpl) mainly derive from structures
of the basal ganglia and the brainstem. These include the internal segment of the globus
pallidus (GPi) and substantia nigra-pars reticulata of the basal ganglia, and the SC,
pretectum, and the acetylcholine-containing LDT of the brainstem. Inputs to MDc
predominately originate from olfactory structures including piriform cortex, endopiriform
nucleus, OT, horizontal limb of diagonal band nucleus and the lateral preoptic area.
Afferents to MDm arise from a greater number and more diverse set of structures than to the
other divisions likely reflecting its involvement in limbic-associated functions. They include:
ACC/ventral pallidum, diagonal band nuclei, the anterior cortical, BLA and basomedial
nuclei of the amygdala, VTA, the substantia nigra-pars compacta (SNc), the
supramammillary nucleus, and the lateral entorhinal cortex (Groenewegen, 1988; Ray and
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Price, 1992; Vertes, 1992). All divisions of MD receive common inputs from several sites
including the reticular nucleus of thalamus, the mesopontine reticular formation, PPT, LDT,
LC and the dorsal and median raphe nuclei of the brainstem (Groenewegen, 1988; Vertes,
1991; Vertes et al., 1999; Krout et al., 2002).
In summary, the foregoing indicates that MDm, largely in contrast to other divisions of MD,
is predominantly interconnected with limbic subcortical and cortical structures, and in this
respect, MDm is much more aligned with the midline nuclei (RE, RH, PV, PT) than with
lateral regions of MD.
3.10 Mediodorsal nucleus, medial division: Functional considerations

As discussed, each division of MD displays a unique set of connections which in general
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constitute a continuum from limbic to motor proceeding medially to laterally in MD. The
functional properties of MD generally parallel this anatomical organization (Groenewegen et
al., 1990; Deniau et al., 1994; Zahm, 2000; Block et al., 2007; Aggleton et al., 2011; Mailly
et al., 2013; Mitchell and Chakraborty, 2013). With regard to MDm, it is strongly
reciprocally linked with the prefrontal cortex and as such its functions significantly overlap
with those of the PFC. A function commonly associated with MD (or MDm) is behavioral
flexibility -- or the capacity to alter behavior to meet changing contingencies (McAlonan et
al., 1993; Hunt and Aggleton, 1998; Block et al., 2007; Dolleman-van der Weel et al., 2009;
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Mitchell and Chakraborty, 2013). Rats with MDm lesions (or inactivation) are unable to
readily switch from one response to another in the face of changing task demands. Although
several factors are likely involved, the deficit is generally attributed to perseverative
responding, or maintaining a previously rewarded response strategy despite its being
incorrect or unrewarded upon changed conditions. For example, Block et al. (2007)
demonstrated that rats with bilateral MD lesions, or disconnecting MD from the mPFC, were
unable to successfully switch from a “response” strategy (e.g., all right turns) to a visually
cued strategy (or vice versa) on a four arm cross-maze. They postulated that MD “directs”
the mPFC to switch strategies and the mPFC, in turn, suppresses incorrect responses in favor
of correct ones to the new paradigm.
Perhaps a more striking example of failures in set shifting with MD (or MDm) lesions
involved the use of a relatively undemanding reference memory task in the water maze
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(Dolleman-van der Weel et al., 2009). MD lesioned rats were slow to acquire a water maze
task, which reportedly was the result of “perseverance” of edge swimming (thigmotaxis)
carried over from pretraining. The rats were also impaired in the change of task conditions in
the probe test from a hidden platform to a visible one. In effect, even though the platform
was visible, MD lesioned rats continued to search for the hidden platform -- a clearly
perseverative response. The deficits in switching strategies described with MD lesions are
characteristic (or a hallmark) of dysfunctions of the prefrontal cortex (Ragozzino et al.,
1999; Birrell and Brown, 2000; Dias and Aggleton, 2000; Stefani et al., 2003; Floresco et
al., 2006; Rich and Shapiro, 2009). The foregoing would suggest that disruption of
communication between these structures leads to perseverative behaviors -- or otherwise
stated, the integrative actions of MD and the mPFC are critical for flexible choice behavior.
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In addition to a role in behavioral flexibility, the mPFC is an important component of an

extended circuitry subserving recognition memory; that is, a circuitry which also includes
the perirhinal cortex, hippocampus and MD (Ennaceur et al., 1996; Norman and Eacott,
2004; Barker et al., 2007; Barker and Warbuton, 2011; Cross et al., 2012). Recognition
memory involves the ability to identify stimuli based on previous experience with them, and
judgments can be made using various types of information such as an object's characteristics
(familiarity) or where (spatial location) or when (temporal order) it was encountered. Barker
et al. (2007) examined the contribution of the mPFC to the different components of
recognition memory showing that mPFC lesions spared single item recognition (novel object
preference) as well as object location (spatial displacement), but significantly disrupted
associative object recognition (object in place task) and recency judgments (temporal order).
With respect to MD, Cross et al. (2012) subsequently demonstrated that MD lesions (or
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disconnecting MD from the mPFC) produced the same types of recognition memory deficits
as seen with mPFC lesions (Barker et al., 2007); that is, intact single item recognition but
marked impairments on associative recognition memory and recency discrimination. These
findings suggest the conjoint action of MD and the mPFC in recognition memory.
3.11 Central medial nucleus

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The intralaminar nuclei (ILt) of thalamus form a conspicuous collection of nuclei in the
medial and dorsal part of the thalamus. The intralaminar thalamic nuclei are located lateral
to the mediodorsal nucleus and embedded within the internal medullary lamina. The
intralaminar nuclei are made up of a rostral group, consisting of the central medial,
paracentral (PC), and central lateral (CL), and a caudal group composed of the
parafascicular (PF) and subparafascicular nuclei (SPF) in rats (Swanson, 2004; Paxinos and
Watson, 2014). The central medial nucleus can be clearly recognized as a centrally located
group of large, deeply staining, flattened cells distinct from midline nuclei lying dorsal and
ventral to it. Laterally, CM is continuous with the paracentral nucleus on both sides.
On the whole, the principal targets of the intralaminar nuclei are regions of the cortex and
the dorsal striatum, with additional projections to the ventral striatum and amygdala. In
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general, the lateral (PC, CL) and caudal (PF, SPF) intralaminar nuclei innervate
sensorimotor regions of the cortex and the dorsal striatum, whereas CM distributes over a
much wider region of the forebrain to both limbic and non-limbic sites (Berendse and
Groenewegen, 1990, 1991; Conde et al., 1990, 1995; Su and Bentivoglio, 1990; Hicks and
Huerta, 1991; Turner and Herkenham, 1991; Brog et al., 1993; Reep and Corwin, 1999; Erro
et al., 2002; Van der Werf et al., 2002; Jasmin et al., 2004; Wang and Shyu, 2004; Hoover
and Vertes, 2007; Vertes et al., 2012, 2104). In this regard, the projections of CM closely
resemble those of the midline nuclei and the MDm (see above) than projections of the other
intralaminar nuclei.
The principal CM targets are anterior and posterior regions of cortex, the claustrum, dorsal
striatum, ACC, OT, and the amygdala. There are distinct differences in projections of the
rostral and caudal CM (Vertes et al., 2012, 2014). The cortical projections of rostral CM
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(CMr) are virtually restricted to anterior regions of cortex, with fibers distributing to AGm,
AC, PL, the dorsolateral orbital and dorsal agranular insular cortices. By contrast, the caudal
CM primarily targets lateral and caudal structures of the cortex including the lateral and
dorsolateral orbital cortices, dorsal and posterior agranular insular cortices, the gustatory/
visceral cortex, the primary somatosensory and motor cortices, and the perirhinal cortex.
Subcortically, rostral CM distributes rostrocaudally throughout C-P, to the anterior core and
shell of ACC, and throughout the BLA of amygdala. Figure 11 shows pronounced
projections from rostral CM to the dorsal striatum, distributing virtually throughout mid-
central and dorsolateral regions of the anterior C-P.
Caudal CM fibers, on the other hand, innervate lateral/ventrolateral regions of C-P and
several nuclei of the amygdala including the anterior, lateral, central, medial, cortical, and
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basal nuclei. With the exception of nucleus accumbens, which essentially only receives input
from the rostral CM, rostral and caudal CM target separate parts of the same structures.
When outputs are combined, however, CM distributes very widely over the cortex, to the
entire dorsal striatum, to the anterior ACC, and to most subnuclei of the amygdala (Vertes et
al., 2012, 2014).
CM lies between the dorsal (PV, PT) and ventral (RE, RH) nuclei of the midline thalamus
and shares connections with each group -- with additional projections to mainly
sensorimotor structures. Specifically, comparable to the ventral midline nuclei, CM

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distributes widely throughout limbic cortices, substantially targeting the lateral and
dorsolateral orbital, dorsal and posterior agranular insular, PL, AC, gustatory/visceral,
ectorhinal and perirhinal cortices. Unlike RE/RH, however, CM does not project to the
hippocampus and only minimally to the entorhinal cortex. On the other hand, comparable to
the dorsal midline nuclei, CM strongly targets the ACC, OT and virtually the entire
amygdala -- with pronounced rostral CM projections to the basolateral nucleus of amygdala.
By contrast with the midline nuclei, however, CM distributes massively to the dorsal
striatum (Fig. 11), essentially blanketing the C-P. In addition, CM is the source of prominent
projections to the primary and secondary motor cortices, and significant but lesser
projections to the somatosensory cortex. Accordingly, CM shares “limbic” subcortical and
cortical projections with the midline nuclei of thalamus (and with MDm), and sensorimotor
projections with the laterally adjacent rostral intralaminar nuclei: PC and CL. In this respect,
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CM appears to bridge the limbic and sensorimotor domains.
Afferent projections to CM, much like those to PT (see above) have not been examined in
detail; no report has systematically described the totality of projections to CM. Loewy and
colleagues, however, using retrograde tracers, described brainstem afferents to CM (Krout
and Loewy, 2000a, 2000b; Krout et al., 2001, 2002) and some reports, as part of larger
investigations of inputs to the thalamus, have traced fibers to CM from various subcortical
and cortical structures.
Evidence gained from descriptions of cortical projections to the thalamus (see above) shows
that the PFC (or the mPFC) strongly targets CM (Reep et al., 1987; Sesack et al., 1989;
Jasmin et al., 2004; Vertes, 2002, 2004; Hoover and Vertes, 2011). Regarding the mPFC,
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ventral (or limbic) regions of the mPFC (i.e., IL, PL and AC) distribute densely to CM,
whereas the dorsally located AGm is the source of weak projections to CM (Vertes, 2002,
2004). By comparison, the orbital and insular cortices distribute moderately to CM with
heaviest input to CM arising from the medial orbital cortex (Shi and Cassell, 1998; Jasmin et
al., 2004; Hoover and Vertes, 2011).
CM receives a diverse set of afferents from subcortical structures, particularly those of the
brainstem. The following subcortical structures have been found to project to CM: the
mesencephalic, pontine, and medullary reticular formation, the serotonergic dorsal raphe,
median raphe and raphe magnus, the cholinergic PPT and LDT nuclei, the nucleus
prepositus hypoglossi, the spinal trigeminal nucleus, the medial and lateral vestibular nuclei,
the parabrachial complex, the LC, nucleus incertus, distinct regions of the PAG, deep layers
of the SC, the nucleus of Darkschewitsch, and the pars reticulata and pars compacta of the
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substantia nigra (Peschanski and Besson, 1984; Jones and Yang, 1985; Vertes et al., 1986,
1999, 2010; Yamasaki et al., 1986; Hallanger et al., 1987; Vertes and Martin, 1988; Vertes,
1991; Villanueva et al., 1998; Bester et al., 1999; Groenewegen et al., 1999; Shiroyama et
al., 1999; Goto et al., 2001; Krout and Loewy, 2000a, 2000b; Krout et al., 2001, 2002;
Olucha-Bordonau et al., 2003). In addition, CM receives input from deep cerebellar nuclei,
the supramammillary nucleus, zona incerta, and the reticular thalamic nucleus (Haroian et
al., 1981; Vertes, 1992; Kolmac and Mitrofanis, 1997; Power et al., 1999; Power and
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Mitrofanis, 2001).
3.12 Central medial nucleus: Functional considerations

As indicated, although partially overlapping, the projections of CM differ from those of the
other intralaminar nuclei, notably CM is a source of rather prominent projections to limbic
sites (Van der Werf et al., 2002; Vertes et al., 2012). Accordingly, the functions of CM would
be expected to differ from those of other intralaminar (ILt) groups and might be more
aligned with functions attributed to the midline nuclei. Unfortunately, the functions of CM
have not for the most part been examined separately from those of the adjacent paracentral
and central lateral nuclei. Most reports examining intralaminar functions have, in fact,
focused on PC and CL, largely to the exclusion of CM. This is likely due to the greater
accessibility of PC/CL, than CM, for behavioral manipulations.
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The functions of the rostral intralaminar (ILt) complex in large measure parallel those of its
main targets, namely, the prefrontal cortex and the dorsal striatum -- and accordingly are
generally described with reference to these targets. In early studies, Mair and colleagues
(Burk and Mair, 1998; Bailey and Mair, 2005) demonstrated that rostral ILt lesions produced
significant deficits on a delayed match to position task which is sensitive to PFC damage
(Mair et al., 1998). In a subsequent report, using the same task, Mair and Hembrook (2008)
showed that the reversible suppression of the rostral ILt with muscimol impaired
performance on the delayed match to position task. Conversely, procedures that either
reduced GABA tone (with FG-7142) to the intralaminar nuclei and or activated (with orexin
A) them improved performance on the task. It was further demonstrated electrical
stimulation of the intralaminar thalamus at low currents similarly enhanced performance on
this task, when applied at the start of the delay period or just prior to the selection of
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appropriate responses. They concluded that ILt neurons “carry response-related information
across brief memory delays and mediate memory-guided responding” (Mair and Hembrook,
2008). Consistent with this, intralaminar neurons in the monkey have been shown to respond
selectively during the delay period of delayed-response tasks signaling the location of visual
targets (Wyder et al., 2003, 2004).
It has further been demonstrated CM/intralaminar thalamus plays a role in striatal-dependent

activities. For instance, Mitchell and Dalrymple-Alford (2006) described a double
dissociation between the effects of ILt or anterior thalamic (ATh) lesions on striatal- or
hippocampal-dependent tasks; namely, on an (egocentric) working memory response-related
task or on an (allocentric) radial arm maze task. Specifically, only ILt lesions impaired
performance on the non-hippocampal-dependent working memory task, whereas ATh
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lesions produced deficits solely on the radial arm maze task. Hembrook and Mair (2011)
similarly found no association between ILt impairments and spatial learning. ILt lesions
significantly disrupted performance and on a visuospatial reaction time task which is
sensitive to striatal damage (Mair et al., 2002), but not on a delayed non-match to sample
radial arm maze task responsive to hippocampal alterations (McDonald and White, 1993;
Mair et al., 1998).
In contrast to the foregoing, Wolff et al. (2008) found that ILt lesions did not disrupt
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performance on an egocentric reference memory task in the water maze -- despite the fact
that dorsal caudate lesions produced severe impairments on a land-based version of this task
(Mitchell and Hall, 1988). Further, Moreau et al. (2013) reported that rats with ILt lesions
exhibited no deficits on a visual discrimination task in the water maze, which is sensitive to
striatal disruption (Packard and McGaugh, 1992). Although several factors could account for
the differing results, including subtle changes in task demands, a most likely explanation
may be that sites of the intralaminar lesions differed across the various studies. This, in turn,
could affect separate, and perhaps non-overlapping, target zones of different sectors of the
dorsal striatum. Moreau et al. (2013) suggested this stating: “Functional heterogeneity
within the striatum and across ILN regions is, however, one complication that is neglected
by a simple ILN-striatal perspective”.
Due in part to the close proximity of the anterior nuclei (ATh) and the intralaminar nuclei of
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the rostral thalamus, several reports (Mair et al., 2003; Bailey and Mair, 2005; Mitchell and
Dalrymple-Alford, 2005, 2006, Wolff et al., 2008; Lopez et al., 2009; Moreau et al., 2013)
have compared the differing functions of these thalamic regions showing that the anterior
nuclei, with connections to the extended hippocampal system, are involved in (allocentric)
spatial working memory, whereas the intralaminar nuclei serve no role in spatial memory but
instead participate in non-hippocampal-related functions such as delayed response activity
and egocentric working memory. Despite this, several studies have described deficits in
spatial memory associated with ILt lesions. Lopez et al. (2009) reported that while rostral
ILt lesions did not alter acquisition or short term (5 day) retrieval in a hippocampal-
dependent spatial memory task in the water maze, such lesions did impair long term (25
day) retrieval on this task – or remote memory. As mentioned above, Hembrook and Mair
(2011) recently showed that ILt lesions did not disrupt spatial memory performance on a
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radial arm task, but altered performance on a striatal dependent visuospatial task. However,
they stated that relatively ‘large’ rostral intralaminar lesions produced deficits on a delayed
non-match to sample radial arm maze task. Earlier studies which found spatial memory
deficits following ILt disruption also involved rather large intralaminar lesions that included
the central medial nucleus (Mair et al., 1998; Burk and Mair, 2001). This further suggests
that the central medial thalamus is more functionally aligned with the midline thalamus than
with other intralaminar nuclei.
4. Conclusion
The midline nuclei of the thalamus, per se, consist of the paraventricular, paratenial,
reuniens and rhomboid nuclei. As described, other cell groups lying on or close to the
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midline of thalamus share properties with the midline nuclei. They notably include the
medial division of the medial dorsal nucleus (MDm) and the central medial nucleus. The
anatomical/functional characteristics of MDm and CM are much more similar to those of the
midline nuclei than to those of lateral divisions of MD or lateral nuclei of the rostral
intralaminar complex, respectively (Figs. 12, 13). Although we did not review the properties
of the intermediodorsal nucleus (IMD) and the interanteromedial nucleus (IAM), which also
lie along the midline of thalamus, previous reports (Van der Werf et al., 2002; Groenewegen
and Witter, 2004) have also shown them to be anatomically and functionally linked to the
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limbic system.
Accordingly, nuclei lying dorsoventrally along the midline/paramidline of the thalamus and
extending virtually throughout the thalamus basically constitute the bulk of the “limbic
thalamus’ (Fig. 1). This group of ‘limbic’ thalamic nuclei are distinctive in that they receive
a wide array of afferents from limbic-related sites of the brainstem and forebrain, project
almost exclusively to limbic subcortical and cortical structures (and the dorsal striatum)
(Figs. 12, 13) and subserve a range of limbic-associated functions. The dorsal midline nuclei
(PV, PT) are primarily involved in affective functions, the ventral midline nuclei (RE, RH) in
cognitive functions.
Acknowledgements
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This work was supported by NIMH grant MH099590 to RPV.
Abbreviations
3V third ventricle
ac anterior commissure
AC anterior cingulate cortex
ACC nucleus accumbens
ACCc nucleus accumbens, core division
ACCs nucleus accumbens, shell division

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ACo anterior commissure
AD anterior dorsal nucleus of thalamus
AGl lateral agranular (primary motor) cortex
AGm medial agranular (secondary motor) cortex
AHN anterior hypothalamic nucleus
AI agranular insular cortex
AId dorsal agranular insular cortex

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AIp posterior agranular insular cortex
AMd anteromedial nucleus of thalamus, dorsal division
ATh anterior thalamus
AV anteroventral nucleus of thalamus
BLA basolateral nucleus of amygdala
BMA basomedial nucleus of amygdala

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BST bed nucleus of stria terminalis
CA1 field CA1 of Ammon's horn
CA3 field CA3 of Ammon's horn
CB cingulum bundle
cc corpus callosum
CEA central nucleus of the amygdala
CEAc central nucleus of amygdala, capsular division
CEAl central nucleus of amygdala, lateral division

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CL central lateral nucleus of thalamus
CLA claustrum
CM central medial nucleus of thalamus
CMc caudal central medial nucleus of thalamus
CMr rostral central medial nucleus of thalamus
C-P caudate-putamen
DG dentate gyrus
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DLG dorsal lateral geniculate nucleus of thalamus
DLO dorsal lateral orbital cortex
DMH dorsomedial hypothalamic nucleus
DR dorsal raphe nucleus
ECl entorhinal cortex, lateral division
fx fornix
GP globus pallidus
GPi globus pallidus, internal segment

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GU gustatory cortex
HF hippocampal formation
IAM interanteromedial nucleus of thalamus
ic internal capsule
IGL intergeniculate leaflet
IL infralimbic cortex
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ILt intralaminar thalamus
IMD intermediodorsal nucleus of thalamus
LA lateral nucleus of amygdala
LC locus coeruleus
LD lateral dorsal nucleus of thalamus
LDT laterodorsal tegmental nucleus
LGN lateral geniculate complex
LH lateral habenula
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LHA lateral hypothalamic area
LO lateral orbital cortex
LP lateral posterior nucleus of thalamus
LS lateral septum
MD mediodorsal nucleus of thalamus
MDc mediodorsal nucleus of thalamus, central division
MDl mediodorsal nucleus of thalamus, lateral division

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MDm mediodorsal nucleus of thalamus, medial division
MDpl mediodorsal nucleus of thalamus, paralamellar division
MGN medial geniculate nucleus of thalamus
MO medial orbital cortex
mPFC medial prefrontal cortex
MR median raphe nucleus
MS medial septum
mt mammillothalamic tract
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OC occipital cortex
OT olfactory tubercle
PAG periaqueductal gray matter
PB parabrachial nucleus
PC paracentral nucleus of thalamus
PF parafascicular nucleus of thalamus

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PFC prefrontal cortex
PL prelimbic cortex
PO posterior nucleus of thalamus
POST postsubiculum
PPT pedunculopontine tegmental nucleus
PRC perirhinal cortex
PT paratenial nucleus of thalamus
PV paraventricular nucleus of thalamus

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RE nucleus reuniens of thalamus
RF reticular formation
RH rhomboid nucleus of thalamus
RSP retrosplenial cortex
RT reticular nucleus of thalamus
SC superior colliculus
SCN suprachiasmatic nucleus of hypothalamus

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SI substantia innominata
slm straum lacunosum-moleculare of CA1 of hippocampus
sm stria medullaris
SMT submedial nucleus of thalamus
SNc substantia nigra, pars compacta
SPF subparafascicular nucleus of thalamus
SUB subiculum
SUBv ventral subiculum

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SUM supramammillary nucleus of hypothalamus
TE temporal cortex
TTd taenia tecta, dorsal division
VA ventral anterior nucleus of thalamus
VAL ventral anterior lateral complex of thalamus
VL ventral lateral nucleus of thalamus

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VLG ventral lateral genciulate nucleus of thalamus
VLO ventrolateral orbital cortex
VM ventral medial nucleus of thalamus
VO ventral orbital cortex
VPL ventral posterolateral nucleus of thalamus
VPM ventral posteromedial nucleus of thalamus
VTA ventral tegmental area
ZI zona incerta
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Highlights
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The thalamus was divided into three main groups: sensorimotor nuclei, limbic nuclei and
nuclei bridging these two domains.
The reuniens and rhomboid of the midline thalamus were linked to cognitive functions.
The paraventricular and paratenial nuclei of the midline thalamus were linked to affective
functions.
The characteristics of the mediodorsal and central medial nuclei are very similar to those
of the midline nuclei.
Nuclei extending dorsoventrally throughout the midline of the thalamus basically

constitute the ‘limbic thalamus’.
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Figure 1.
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Schematic representation of three rostrocaudally (A-C) aligned sections through the

diencephalon depicting (in dark gray) the locations of dorsoventrally oriented nuclei along
the midline/paramidline of the thalamus, which together with the anterior nuclei of
thalamus, constitute the ‘limbic thalamus’. They include the paraventricular (PV), paratenial
(PT), reuniens (RE) and rhomboid (RH) nuclei of the midline thalamus, the medial division
of the mediodorsal nucleus (MDm), the central medial nucleus (CM) of the rostral
intralaminar complex, the interanteromedial nucleus (IAM) and the intermediodorsal (IMD)
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nucleus. Sections modified from Swanson (2004). See list for abbreviations.
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Figure 2.
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Low magnification darkfield photomicrographs showing patterns of labeling in the dorsal

(A) and ventral hippocampus (B,C) produced by an injection of PHA-L in nucleus reuniens
of the midline thalamus. Note the dense concentration of labeled fibers restricted to the
stratum lacunosum moleculare of CA1 of the dorsal (A) and ventral (B) hippocampus and
the molecular layer of the ventral subiculum (C). See list for abbreviations. Scale bar for A =
600 μm; for B,C = 1000 μm. Modified from Vertes et al. (2006).
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Figure 3.
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A,B: low magnification darkfield photomicrographs of transverse sections through the

rostral forebrain showing patterns of labeling within the medial prefrontal cortex produced
by an injection of PHA-L in nucleus reuniens of the midline thalamus. Note the presence of
pronounced numbers of labeled fibers in the infralimbic (IL), prelimbic (PL), anterior
cingulate (AC) and medial (frontal) agranular (AGm) cortices, stronger in IL and PL than in
AC and AGm Note additional labeling in the claustrum (CLA), the rostral pole of nucleus
accumbens (ACC) and the dorsal agranular insular cortex (AId). C: high magnification
darkfield photomicrograph from A (arrows) showing labeled fibers in all layers of IL, PL
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and AC, most densely concentrated in layers 1 and 5/6, and mediolaterally aligned fibers in
the middle layers of these fields, oriented parallel to the cell layers. See list for
abbreviations. Scale bar for A,B = 1000 μm; for C = 250 μm. Modified from Vertes et al.
(2006).
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Figure 4.
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Low (A) and high (B,C) magnification light-field photomicrographs depicting retrogradely
labeled cells in the ventral subicular complex of the hippocampus produced by a Fluorogold
injection in nucleus reuniens of the midline thalamus. As shown, pronounced numbers of
labeled cells extended dorsal-ventrally throughout the subiculum (SUB) within the ventral
subiculum and the postsubiculum (POST). B,C: Clusters of labeled cells dorsally in the
ventral subiculum (arrow in A) at higher levels of magnification. See list for abbreviations.
Scale bar for A = 325 μm; for B,C = 65 μm. Modified from McKenna and Vertes (2004).
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Figure 5.
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Darkfield photomicrograph of a transverse section through the diencephalon showing

patterns of labeling within nuclei of the midline thalamus produced by a PHA-L injection in
the infralimbic cortex. Note dense labeling virtually confined to the paraventricular and
medial division of the mediodorsal nucleus (MDm), dorsally, and the nucleus reuniens (RE),
ventrally. See list for abbreviations. Scale bar = 450 μm. Modified from Vertes (2002).
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Figure 6.
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Series of electron micrographic sections through the nucleus reuniens of the midline
thalamus (a-d) showing asymmetric contacts of a single PHA-L labeled (F) fibers from the
medial prefrontal cortex onto a labeled dendritic shaft, identified by the presence of
numerous silver intensified gold deposits (arrows in D) of a nucleus reuniens cell
retrogradely from a Fluorogold injection in the ventral hippocampus. Note also the presence
of asymmetric contacts of an unlabeled fiber (A) on the same labeled dendrite segment (D).
Scale bar, 1 μm. Modified from Vertes et al. (2007).
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Figure 7.
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Low (A) and high (B) magnification darkfield photomicrographs of a transverse section
through the anterior forebrain showing patterns of labeling in the dorsal and ventral striatum
produced by a PHA-L injection in the rhomboid nucleus of the midline thalamus. B taken
from A (arrowheads). Note dense labeling in the nucleus accumbens (ACC) and adjacent
ventromedial parts of the dorsal striatum. See list for abbreviations. Scale bar: for A = 750
μm; for B = 400 μm. Modified from Vertes et al. (2006).
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Figure 8.
Low magnification darkfield photomicrographs of transverse sections through anterior
forebrain showing patterns of labeling in the nucleus accumbens (ACC) (A) and the bed
nucleus of the stria terminalis (BST) (B) produced by a PHA-L injection in the anterior
paraventricular nucleus of the midline thalamus. Note the pronounced labeling in both the
shell and core of ACC, with additional labeling in the adjacent lateral septum (LS) as well as
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in BST above and below the anterior commissure. See list for abbreviations. Scale bar = 500
μm. Modified from Vertes and Hoover (2008).
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Figure 9.
A-D: Series of low magnification darkfield photomicrographs of transverse sections
rostrocaudally (A-D) through the forebrain depicting patterns of labeling within the
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amygdala produced by a PHA-L injection in the posterior paraventricular nucleus of the

midline thalamus. A,B: Note dense labeling in the central (CEA), basomedial (BMA) and
basolateral (BLA) nuclei of amygdala, and marked but less pronounced labeling in parts of
the medial, lateral (LA) and anterior cortical nuclei of the amygdala. C,D: Note prominent
labeling caudally within the amygdala mainly confined to BMA and BLA. See list for
abbreviations. Scale bar = 750 μm. Modified from Vertes and Hoover (2008).
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Figure 10.
A-C: Series of rostrocaudally (A-C) aligned low magnification darkfield photomicrographs
of transverse sections through the anterior forebrain depicting patterns of labeling within the
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medial prefrontal cortex (mPFC) produced by a PHA-L injection into the paratenial nucleus
of the midline thalamus. Note intense labeling along the ventral medial wall of the mPFC
mainly confined to the prelimbic (PL) (A-C), medial orbital (MO) (A,B) and infralimbic (C)
(IL) cortices. As depicted, labeling was particularly dense in layers 1 and 3 of these
prefrontal cortical fields. See list for abbreviations. Scale bar = 750 μm. Modified from
Vertes and Hoover (2008).
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Figure 11.
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Low power lightfield photomicrographs of four rostrocaudally aligned (A-D) transverse

sections through the rostral forebrain showing patterns of labeling in the dorsal striatum (C-
P) produced by a PHA-L injection rostrally in the central medial nucleus of the thalamus.
Note dense labeling spread throughout C-P, concentrated rostrally (A,B), dorsoventrally
within the mid-central C-P, and caudally (C,D) within the medial/dorsomedial half of C-P.
See list for abbreviations. Scale bar for A = 975 μm; for B,C = 1000 μm; for D = 950 μm.
Modified from Vertes et al. (2012).
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Figure 12.
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Summary diagram comparing and contrasting the main projection sites of the
paraventricular PVP, paratenial (PT), reuniens (RE) and rhomboid (RH) nuclei of the
midline thalamus to the cortex, basal forebrain, amygdala and hypothalamus. See list for
abbreviations.
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Figure 13.
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Summary diagram comparing and contrasting the main projection sites of the rostral (CMr)
and caudal (CMc) central medial nucleus and the medial division of the mediodorsal nucleus
(MDm) of thalamus to the cortex, basal forebrain and amygdala. See list for abbreviations.

Circuitos Limbico-Talamico

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LIMBIC CIRCUITRY OF THE MIDLINE THALAMUS

Despite the fact that corticothalamic projections significantly outnumber thalamocortical

cell groups were designated as ‘non-specific’ based on their (presumed) widespread

2. An alternative classification for nuclei of the thalamus

3. The limbic thalamus

degree of involvement in sensorimotor or limbic functions. Specifically, while it is

3.2 Nucleus reuniens

In addition to the hippocampus, RE is a rich source of projections to several cortical sites

2004). As depicted in Figure 4, a Fluorogold injection in RE gave rise to a dense band of

hippocampus -- thus completing an important functional loop between these structures.

3.3 Rhomboid nucleus

mesencephalic RF, SC, and the anterior pretectal nucleus

3.4 Reuniens and rhomboid nuclei: Functional Considerations

al., 2013). In accord with a RE involvement mPFC-associated functions (Dolleman-van der

the mPFC (strategy-shifting) for successful completion. Only hippocampal inactivation

3.5 Paraventricular nucleus

2011; Li and Kirouac, 2012).

3.6 Paratenial nucleus

nuclei including PV. Nonetheless, an understanding of major sources of afferents to PT has

3.7 Differential projections of the paraventricular and paratenial nuclei

3.8 Paraventricular nucleus: Functional considerations

The paraventricular nucleus is activated by wide range of stressors such as fear/anxiety,

instance, c-fos levels in PV are enhanced in anticipation of feeding in food-deprived rats,

3.9 Mediodorsal nucleus, medial division

The different segments of MD are characterized by distinct input-output relationships and

3.10 Mediodorsal nucleus, medial division: Functional considerations

In addition to a role in behavioral flexibility, the mPFC is an important component of an

3.11 Central medial nucleus

sensorimotor structures. Specifically, comparable to the ventral midline nuclei, CM

CM appears to bridge the limbic and sensorimotor domains.

3.12 Central medial nucleus: Functional considerations

It has further been demonstrated CM/intralaminar thalamus plays a role in striatal-dependent

This work was supported by NIMH grant MH099590 to RPV.

AC anterior cingulate cortex

ACC nucleus accumbens

ACCc nucleus accumbens, core division

ACCs nucleus accumbens, shell division

ACo anterior commissure

AD anterior dorsal nucleus of thalamus

AGl lateral agranular (primary motor) cortex

AGm medial agranular (secondary motor) cortex

AHN anterior hypothalamic nucleus

AI agranular insular cortex

AId dorsal agranular insular cortex

AIp posterior agranular insular cortex

AMd anteromedial nucleus of thalamus, dorsal division

ATh anterior thalamus

AV anteroventral nucleus of thalamus

BLA basolateral nucleus of amygdala

BMA basomedial nucleus of amygdala

BST bed nucleus of stria terminalis

CA1 field CA1 of Ammon's horn

CA3 field CA3 of Ammon's horn

CEA central nucleus of the amygdala

CEAc central nucleus of amygdala, capsular division

CEAl central nucleus of amygdala, lateral division