Abstract
Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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References
Somogyi, P., Tamas, G., Lujan, R. & Buhl, E. H. Salient features of synaptic organisation in the cerebral cortex. Brain Res. Brain Res. Rev. 26, 113–135 (1998).
Ramón y Cajal, S. Textura del sistema nervioso del hombre y de los vertebrados (Moya, Madrid, 1899). English translation: Histology of the Nervous System of Man and Vertebrates (Oxford Univ. Press, New York, 1995)
Lorente de Nó, R. La corteza cerebral de ratón. (Primera contribución - La corteza acústica). Trabajos del Laboratorio de Investigaciones Biológicas de la Universidad de Madrid 20, 41–78 (1922). English translation: Fairén, A., Regidor, J. & Kruger, L. The cerebral cortex of the mouse (a first contribution - the “acoustic” cortex). Somatosens. Mot. Res. 9, 3–36 (1992).
Szentagóthai, J. The neuron network of the cerebral cortex: a functional interpretation. Proc. R. Soc. Lond. B Biol. Sci. 201, 219–248 (1978).
Fairén, A., DeFelipe, J. & Regidor, J. in Cerebral Cortex vol. 1 Cellular Components of the Cerebral Cortex (eds, Peters, A. & Jones, E. G.) 201–253 (Plenum, New York, 1984).
Lund, J. S. Anatomical organization of macaque monkey striate visual cortex. Ann. Rev. Neurosci. 11, 253–288 (1988).
Douglas, R. J. & Martin, K. A. C. in The Synaptic Organization of the Brain (ed. Shepherd, G. M.) 459–511 (Oxford Univ. Press, Oxford, 1998).
Gupta, A., Wang, Y. & Markram, H. Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287, 273–278 (2000).
Lacaille, J. C., Kunkel, D. D. & Schwartzkroin, P. A. in The Hippocampus: New Vistas (eds Chan-Palay, V. & Kohler, C.) 287–305 (Liss, 1989).
Maccaferri, G. & Lacaille, J. C. Interneuron diversity series: Hippocampal interneuron classifications - making things as simple as possible, not simpler. Trends Neurosci. 26, 564–571 (2003).
Cauli, B. et al. Molecular and physiological diversity of cortical nonpyramidal cells. J. Neurosci. 17, 3894–3906 (1997).
Kawaguchi, Y. Physiological, morphological, and histochemical characterization of three classes of interneurons in rat neostriatum. J. Neurosci. 13, 4908–4923 (1993).
Toledo-Rodriguez, M. et al. Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex. Cereb. Cortex 14, 1310–1327 (2004).
Kostyuk, P. G. Synaptic mechanism of central inhibition. Prog. Brain Res. 22, 67–85 (1968).
Huang, Z. J., Di Cristo, G. & Ango, F. Development of GABA innervation in the cerebral and cerebellar cortices. Nature Rev. Neurosci. 8, 673–686 (2007).
Bayraktar, T., Welker, E., Freund, T. F., Zilles, K. & Staiger, J. F. Neurons immunoreactive for vasoactive intestinal polypeptide in the rat primary somatosensory cortex: morphology and spatial relationship to barrel-related columns. J. Comp. Neurol. 420, 291–304 (2000).
Porter, J. T. et al. Properties of bipolar VIPergic interneurons and their excitation by pyramidal neurons in the rat neocortex. Eur. J. Neurosci. 10, 3617–3628 (1998).
Rozov, A., Jerecic, J., Sakmann, B. & Burnashev, N. AMPA receptor channels with long-lasting desensitization in bipolar interneurons contribute to synaptic depression in a novel feedback circuit in layer 2/3 of rat neocortex. J. Neurosci. 21, 8062–8071 (2001).
Zilberter, Y., Kaiser, K. M. & Sakmann, B. Dendritic GABA release depresses excitatory transmission between layer 2/3 pyramidal and bitufted neurons in rat neocortex. Neuron 24, 979–988 (1999).
Scorcioni, R. & Ascoli, G. A. Algorithmic extraction of morphological statistics from electronic archives of neuroanatomy. Lect. Notes Comput. Sci. 2084, 30–37 (2001).
Rall, W. Electrophysiology of a dendritic neuron model. Biophys. J. 2, 145–167 (1962).
Sholl, D. A. Dendritic organization in the neurons of the visual cortex and motor cortices of the cat. J. Anat. 87, 387–406 (1953).
Sholl, D. A. The organization of the visual cortex in the cat. J. Anat. 89, 33–46 (1953).
Cannon, R. C., Wheal, H. V. & Turner, D. A. Dendrites of classes of hippocampal neurons differ in structural complexity and branching patterns. J. Comp. Neurol. 413, 619–633 (1999).
Li, Y., Brewer, D., Burke, R. E. & Ascoli, G. A. Developmental changes in spinal motoneuron dendrites in neonatal mice. J. Comp. Neurol. 483, 304–317 (2005).
Uylings, H. B. M. & van Pelt, J. Measures for quantifying dendritic arborizations. Netw. Comput. Neural Syst. 13, 397–414 (2002).
Gray, E. G. Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscopic study. J. Anat. 93, 420–433 (1959).
Colonnier, M. Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscope study. Brain Res. 9, 268–287 (1968).
Peters, A., Palay, S. L. & Webster, H. deF. The Fine Structure of the Nervous System. Neurons and their Supporting Cells (Oxford Univ. Press, New York, 1991).
Gulyás, A. I., Megías, M., Emri, Z. & Freund, T. F. Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus. J. Neurosci. 19, 10082–10097 (1999).
Butt, S. J. et al. The temporal and spatial origins of cortical interneurons predict their physiological subtype. Neuron 48, 591–604 (2005).
Dumitriu, D., Cossart, R., Huang, J. & Yuste, R. Correlation between axonal morphologies and synaptic input kinetics of interneurons from mouse visual cortex. Cereb. Cortex 17, 81–91 (2007).
Sik, A., Ylinen, A., Penttonen, M. & Buzsáki, G. Inhibitory CA1-CA3-hilar region feedback in the hippocampus. Science 265, 1722–1724 (1994).
Sik, A., Penttonen, M., Ylinen, A. & Buzsáki, G. Hippocampal CA1 interneurons: an in vivo intracellular labeling study. J. Neurosci. 15, 6651–6665 (1995).
Sik, A., Penttonen, M. & Buzsáki, G. Interneurons in the hippocampal dentate gyrus: an in vivo intracellular study. Eur. J. Neurosci. 9, 573–588 (1997).
Jinno, S. et al. Neuronal diversity in GABAergic long-range projections from the hippocampus. J. Neurosci. 27, 8790–8804 (2007).
Miyashita, T. & Rockland, K. S. GABAergic projections from the hippocampus to the retrosplenial cortex in the rat. Eur. J. Neurosci. 26, 1193–1204 (2007).
Tomioka, R. & Rockland, K. S. Long-distance corticocortical GABAergic neurons in the adult monkey white and gray matter. J. Comp. Neurol. 505, 526–538 (2007).
Tamas, G., Somogyi, P. & Buhl, E. H. Differentially interconnected networks of GABAergic interneurons in the visual cortex of the cat. J. Neurosci. 18, 4255–4270 (1998).
Somogyi, P. & Cowey, A. Combined Golgi and electron microscopic study on the synapses formed by double bouquet cells in the visual cortex of the cat and monkey. J. Comp. Neurol. 195, 547–566 (1981).
Somogyi, P. & Cowey, A. in Cerebral Ccortex vol. 1 Cellular Components of the Cerebral Cortex (eds Peters, A. & Jones, E. G.) 337–360 (Plenum, New York, 1984).
White, E. L. Cortical Circuits. Synaptic Organization of the Cerebral Cortex (Birkhauser, Boston, 1989).
Valverde, F. The organization of area 18 in the monkey: Golgi study. Anat. Embryol. 154, 305–334 (1978).
Ballesteros-Yánez, I. et al. The double bouquet cell in the human cerebral cortex and a comparison with other mammals. J. Comp. Neurol. 486, 344–360 (2005).
Binzegger, T., Douglas, R. J. & Martin, K. A. Stereotypical bouton clustering of individual neurons in cat primary visual cortex. J. Neurosci. 27, 12242–12254 (2007).
Tamas, G., Buhl, E. H. & Somogyi, P. Massive autaptic self-innervation of GABAergic neurons in cat visual cortex. J. Neurosci. 17, 6352–6364 (1997).
Peters, A. & Harriman, K. M. Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. I. Morphometric analysis. J. Neurocytol. 19, 154–174 (1990).
DeFelipe, J., Hendry, S. H., Jones, E. G. & Schmechel, D. Variability in the terminations of GABAergic chandelier cell axons on initial segments of pyramidal cell axons in the monkey sensory-motor cortex. J. Comp. Neurol. 231, 364–384 (1985).
Somogyi, P. & Klausberger, T. Defined types of cortical interneuron structure space and spike timing in the hippocampus. J. Physiol. 562, 9–26 (2005).
DeFelipe, J. (ed.) J. Neurocytol. 31, 181–416 (2002).
McBain, C. J. & Fisahn, A. Interneurons unbound. Nature Rev. Neurosci. 2, 11–23 (2001).
Bennett, M. V. & Zukin, R. S. Electrical coupling and neuronal synchronization in the mammalian brain. Neuron 41, 495–511 (2004).
Tamas, G., Buhl, E. H., Lörincz, A. & Somogyi, P. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Nature Neurosci. 3, 366–371 (2000).
Fukuda, T. & Kosaka, T. Ultrastructural study of gap junctions between dendrites of parvalbumin-containing GABAergic neurons in various neocortical areas of the adult rat. Neuroscience 120, 5–20 (2003).
Zoli, M., Jansson, A., Sykova, E., Agnati, L. F. & Fuxe, K. Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol. Sci. 20, 142–150 (1999).
Vizi, E. S. Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the central nervous system. Pharmacol. Rev. 52, 63–89 (2000).
Monyer, H. & Markram, H. Interneuron diversity series: Molecular and genetic tools to study GABAergic interneuron diversity and function. Trends Neurosci. 27, 90–97 (2004).
Ray, A., Zoidl, G., Weickert, S., Wahle, P. & Dermietzel, R. Site-specific and developmental expression of pannexin1 in the mouse nervous system. Eur. J. Neurosci. 21, 3277–3290 (2005).
Kamme, F. et al. Single-cell microarray analysis in hippocampus CA1: demonstration and validation of cellular heterogeneity. J. Neurosci. 23, 3607–3615 (2003).
Sugino, K. et al. Molecular taxonomy of major neuronal classes in the adult mouse forebrain. Nature Neurosci. 9, 99–107 (2006).
DeFelipe, J. Chandelier cells and epilepsy. Brain 122, 1807–1822 (1999).
Llinás, R. R., Grace, A. A. & Yarom, Y. In vitro neurons in mammalian cortical layer 4 exhibit intrinsic oscillatory activity in the 10- to 50-Hz frequency range. Proc. Natl Acad. Sci. USA 88, 897–901 (1991).
Hutcheon, B. & Yarom, Y. Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci. 23, 216–222 (2000).
Pike, F. G. et al. Distinct frequency preferences of different types of rat hippocampal neurones in response to oscillatory input currents. J. Physiol. 529, 205–213 (2000).
Klausberger, T. et al. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421, 844–848 (2003).
Goldberg, J. H., Tamas, G. & Yuste, R. Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation. J. Physiol. 551, 49–65 (2003).
Ali, A. B., Bannister, A. P. & Thomson, A. M. Robust correlations between action potential duration and the properties of synaptic connections in layer 4 interneurones in juvenile and adult neocortical slices. J. Physiol. 580, 149–169 (2007).
Kröner, S., Krimer, L. S., Lewis, D. A. & Barrionuevo, G. Dopamine increases inhibition in the monkey dorsolateral prefrontal cortex through cell type-specific modulation of interneurons. Cereb. Cortex 17, 1020–1032 (2007).
Thomson, A. M., West, D. C. & Deuchars, J. Properties of single axon EPSPs elicited in spiny interneurones by action potentials in pyramidal neurones in slices of rat neocortex. Neuroscience 69, 727–738 (1995).
Ali, A. B. & Thomson, A. M. Synaptic a5 subunit containing GABAA receptors mediate IPSPs elicited by dendrite-targeting cells in rat neocortex. Cereb. Cortex 18, 1260–1271 (2008).
Markram, H. & Tsodyks, M. Redistribution of synaptic efficacy between neocortical pyramidal neurons. Nature 382, 807–810 (1996).
Kullmann, D. M. & Lamsa, K. P. Long-term synaptic plasticity in hippocampal interneurons. Nature Rev. Neurosci. 8, 687–699 (2007).
Pelletier, J. G. & Lacaille, J. C. Long-term synaptic plasticity in hippocampal feedback inhibitory networks. Prog. Brain Res. 169, 241–250 (2008).
Thomson, A. M., Deuchars, J. & West, D. C. Single axon EPSPs in neocortical interneurones exhibit pronounced paired pulse facilitation. Neuroscience 54, 347–360 (1993).
Thomson, A. M., West, D. C., Wang, Y. & Bannister, A. P. Synaptic connections and small circuits involving excitatory and inhibitory neurones in layers 2 to 5 of adult rat and cat neocortex: triple intracellular recordings and biocytin-labelling in vitro. Cereb. Cortex 12, 936–953 (2002).
West, D. C., Mercer, A., Kirchhecker, S., Morris, O. T. & Thomson, A. M. Layer 6 cortico- thalamic pyramidal cells preferentially innervate interneurons and generate facilitating EPSPs. Cereb. Cortex 16, 200–211 (2006).
Maffei, A., Nataraj, K., Nelson, S. B. & Turrigiano, G. G. Potentiation of cortical inhibition by visual deprivation. Nature 443, 81–84 (2006).
Kawaguchi, Y. & Shindou, T. Noradrenergic excitation and inhibition of GABAergic cell types in rat frontal cortex. J. Neurosci. 18, 6963–6976 (1998).
Xiang, Z., Huguenard, J. R. & Prince, D. A. Cholinergic switching within neocortical inhibitory networks. Science 281, 985–988 (1998).
Férézou, I. et al. 5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons. J. Neurosci. 22, 7389–7397 (2002).
Bacci, A., Huguenard, J. R. & Prince, D. A. Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids. Nature 431, 312–316 (2004).
Bodor, A. L. et al. Endocannabinoid signaling in rat somatosensory cortex: laminar differences and involvement of specific interneuron types. J. Neurosci. 25, 6845–6856 (2005).
Gulledge, A. T., Park, S. B., Kawaguchi, Y. & Stuart, G. J. Heterogeneity of phasic cholinergic signaling in neocortical neurons. J. Neurophysiol. 97, 2215–2229 (2007).
Buzsáki, G. Large-scale recording of neuronal ensembles. Nature Neurosci. 7, 446–451 (2004).
Csicsvari, J., Hirase, H., Czurkó, A., Mamiya, A. & Buzsáki, G. Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving rat. J. Neurosci. 19, 274–287 (1999).
Barthó, P. et al. Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. J. Neurophysiol. 92, 600–608 (2004).
Klausberger, T. et al. Spike timing of dendrite-targeting bistratified cells during hippocampal network oscillations in vivo. Nature Neurosci. 7, 41–47 (2004).
Goldberg, J. H., Lacefield, C. O. & Yuste, R. Global dendritic calcium spikes in mouse layer 5 low threshold spiking interneurones: implications for control of pyramidal cell bursting. J. Physiol. 558, 465–478 (2004).
Tyner, C. F. The naming of neurons: applications of taxonomic theory to the study of cellular populations. Brain Behav. Evol. 12, 75–96 (1975).
Bota, M. & Swanson, L. W. The neuron classification problem. Brain Res. Rev. 56, 79–88 (2007).
Miyoshi, G., Butt, S. J., Takebayashi, H. & Fishell, G. Physiologically distinct temporal cohorts of cortical interneurons arise from telencephalic Olig2-expressing precursors. J. Neurosci. 27, 7786–7798 (2007).
Tsiola, A., Hamzei-Sichani, F., Peterlin, Z. & Yuste, R. Quantitative morphologic classification of layer 5 neurons from mouse primary visual cortex. J. Comp. Neurol. 461, 415–428 (2003).
Wonders, C. P. & Anderson, S. A. The origin and specification of cortical interneurons. Nature Rev. Neurosci. 7, 687–696 (2006).
Thomson, A. M. & Lamy, C. Functional maps of neocortical local circuitry. Front. Neurosci. 1, 19–42 (2007).
Swadlow, H. A. Fast-spike interneurons and feedforward inhibition in awake sensory neocortex. Cereb. Cortex 13, 25–32 (2003).
Goldberg, J. H., Tamas, G., Aronov, D. & Yuste, R. Calcium microdomains in aspiny dendrites. Neuron 40, 807–821 (2003).
Goldberg, J. H., Yuste, R. & Tamas, G. Ca2+ imaging of mouse neocortical interneurone dendrites: contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+ dynamics. J. Physiol. 551, 67–78 (2003).
Kaiser, K. M., Zilberter, Y. & Sakmann, B. Back-propagating action potentials mediate calcium signalling in dendrites of bitufted interneurons in layer 2/3 of rat somatosensory cortex. J. Physiol. 535, 17–31 (2001).
Kaiser, K. M., Zilberter, Y. & Sakmann, B. Postsynaptic calcium influx at single synaptic contacts between pyramidal neurons and bitufted interneurons in layer 2/3 of rat neocortex is enhanced by backpropagating action potentials. J. Neurosci. 24, 1319–1329 (2004).
Povysheva, N. V. et al. Electrophysiological differences between neurogliaform cells from monkey and rat prefrontal cortex. J. Neurophysiol. 97, 1030–1039 (2007).
Ascoli, G. A. Mobilizing the base of neuroscience data: the case of neuronal morphologies. Nature Rev. Neurosci. 7, 318–324 (2007).
Ascoli, G. A., Donohue, D. E. & Halavi, M. NeuroMorpho.Org: a central resource for neuronal morphologies. J. Neurosci. 27, 9247–9251 (2007).
Markram, H. The Blue Brain Project. Nature Rev. Neurosci. 7, 153–160 (2006).
Martinotti, C. Contributo allo studio della corteccia cerebrale, ed all'origine centrale dei nervi. Ann. Freniatr. Sci. Affini. 1, 14–381 (1889).
Marin-Padilla, M. in Cerebral Cortex: Cellular Components of the Cerebral Cortex (eds Peters, A. & Jones, E. G.) 447–478 (Plenum, New York, 1984).
Wang, Y. et al. Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat. J. Physiol. 561, 65–90 (2004).
Kawaguchi, Y. & Kubota, Y. GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb. Cortex 7, 476–486 (1997).
Tamás, G., Lorincz, A., Simon, A. & Szabadics, J. Identified sources and targets of slow inhibition in the neocortex. Science 299, 1902–1905 (2003).
Toledo-Rodriguez, M. Genetical, Anatomical and Electrical Determinants of Neuronal Diversity. Thesis, Weizmann Inst. Sci.
Goldberg, J. H. & Yuste, R. Space matters: local and global dendritic Ca2+ compartmentalization in cortical interneurons. Trends Neurosci. 28, 158–167 (2005).
Acknowledgements
The authors are grateful to funding agencies in their respective countries for supporting this work. The Gobierno de Navarra/Nafarroako Gobernua and the town and people of Petilla are acknowledged for graciously hosting the meeting that originated this document. Special thanks are due to A. Rowan, who attended the Petilla meeting and greatly contributed to establishing the initial vision for this report.
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Supplementary information S1 (box)
Author addresses (PDF 120 kb)
Supplementary information S2 (box)
Nomenclature of morphological features. (PDF 105 kb)
Supplementary information S3 (box)
Nomenclature of molecular features (PDF 91 kb)
Supplementary information S4 (box)
Nomenclature of physiological features. (PDF 93 kb)
Supplementary information S5 (figure)
Somato-dendritic characteristics of cortical interneurons. (PDF 107 kb)
Supplementary information S6 (figure)
Target specificity of cortical interneurons. (PDF 335 kb)
Supplementary information S7 (figure)
Combining morphological and functional criteria. (PDF 433 kb)
Supplementary information S8 (figure)
Electrophysiological and morphological characteristics of primate cortical interneurons. (PDF 437 kb)
Supplementary information S9 (figure)
Near-threshold differences in discharge patterns of neocortical FS interneurons. (PDF 334 kb)
Supplementary information S10 (figure)
Differences between species: prefrontal cortex neurogliaform (NGF) cells. (PDF 316 kb)
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The Petilla Interneuron Nomenclature Group (PING). Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex. Nat Rev Neurosci 9, 557–568 (2008). https://doi.org/10.1038/nrn2402
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DOI: https://doi.org/10.1038/nrn2402
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