Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothal... more Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus fire exclusively during waking and support many physiological functions. We investigated the role of the endovanilloid N-oleoyldopamine (OLDA) in TMN, where dopamine synthesis and its conjugation with oleic acid likely occur. We show that several known targets of OLDA including TRPV1 and cannabinoid receptors are expressed in HA neurons. In contrast to capsaicin, which failed to increase firing of HA neurons in TRPV1 knockout mice (TRPVI KO), OLDA was still able to induce excitation. This excitation was not sensitive to the blockade of cannabinoid receptors 1 and 2 and could result from OLDA interaction with GPR119, as the ligand of GPR119, oleoylethanolamide (OEA), also increased the firing of HA neurons. However, we ruled out this possibility as OEA- (but not OLDA-) excitation was abolished by the PPAR (peroxisome proliferator activated receptor) alpha antagonist MK886. The dopami...
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic... more N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed. Under sulpiride OLDA slightly excited SNc DA neurons, an action abolished upon combined application of the cannabinoid1 and 2 receptor antagonists AM251 and AM630. In ventral tegmental area (VTA) DA neurons from TRPV1 KO mice a transient inhibition of firing by OLDA was observed. Thus OLDA modulates the firing of nigrostriatal DA neurons through interactions with TRPV1, cannabinoid receptors and dopami...
High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakeful... more High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakefulness, and their firing rate is highest during waking and lowest during rapid eye movement sleep. The TM neurons receive a prominent innervation from sleep-active gamma-aminobutyric acidergic (GABAergic) neurons in the ventrolateral preoptic nucleus, which inhibits them during sleep. They also receive an excitatory input from the orexin- and dynorphin-containing neurons in the lateral hypothalamus, which are critically involved in sleep regulation and whose dysfunction causes narcolepsy. We have used intracellular recordings and immunohistochemistry to study if orexin neurons exert control over the GABAergic inputs to TM neurons in rat hypothalamic slices. Dynorphin suppressed GABAergic inputs and thus disinhibits the TM neurons, acting in concert with orexin to increase the excitability of these neurons. In contrast, both orexin-A and orexin-B markedly increased the frequency of GABAergic potentials, while co-application of orexin and dynorphin produced responses similar to dynorphin alone. Thus, orexins excite TM neurons directly and by disinhibition, gated by dynorphin. These data might explain some of the neuropathology of narcolepsy.
... 16, 15231537. 26. Monti, JM, Pellejero, T., and Jantos, H. (1986) Effects of H ... 69. Mille... more ... 16, 15231537. 26. Monti, JM, Pellejero, T., and Jantos, H. (1986) Effects of H ... 69. Miller, JD, Farber, J., Gatz, P., Roffwarg, H., and German, DC (1983) Activity of mesen-cephalic dopamine and non-dopamine neurons across stages of sleep and walking in the rat. Brain Res. ...
Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippo... more Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippocampus are shown to be prolonged by 4-aminopyridine (4-AP). This action can explain the enormous increase in synaptic transmitter release caused by 4-AP.
Hippocampal high-frequency (200 Hz, &... more Hippocampal high-frequency (200 Hz, 'ripple') oscillations were recorded in the CA1 area of behaving rats. The histamine H1-receptor antagonist pyrilamine facilitated while the H2-antagonist zolantidine (5 mg/kg i.p) transiently decreased ripple occurrence. Thioperamide, an H3 antagonist, had no effect. The 5-HT1A-receptor antagonist WAY100635 (50 microg i.c.v.) reduced the occurrence and the intrinsic frequency of ripples. The 5-HT3-receptor antagonist Y-25130 (i.c.v.) increased the number but reduced the amplitude of ripples. All the treatments affected sharp-waves and ripple oscillations to the same extent. Changes of ripple occurrence were not secondary to alterations of behavior. In the light of these divergent actions via different receptor subtypes the net effect of aminergic innervations will be determined by their state-dependent activities and mutual interactions as well as receptor localizations.
Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothal... more Histaminergic (HA) neurons located in the tuberomamillary nucleus (TMN) of the posterior hypothalamus fire exclusively during waking and support many physiological functions. We investigated the role of the endovanilloid N-oleoyldopamine (OLDA) in TMN, where dopamine synthesis and its conjugation with oleic acid likely occur. We show that several known targets of OLDA including TRPV1 and cannabinoid receptors are expressed in HA neurons. In contrast to capsaicin, which failed to increase firing of HA neurons in TRPV1 knockout mice (TRPVI KO), OLDA was still able to induce excitation. This excitation was not sensitive to the blockade of cannabinoid receptors 1 and 2 and could result from OLDA interaction with GPR119, as the ligand of GPR119, oleoylethanolamide (OEA), also increased the firing of HA neurons. However, we ruled out this possibility as OEA- (but not OLDA-) excitation was abolished by the PPAR (peroxisome proliferator activated receptor) alpha antagonist MK886. The dopami...
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic... more N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed. Under sulpiride OLDA slightly excited SNc DA neurons, an action abolished upon combined application of the cannabinoid1 and 2 receptor antagonists AM251 and AM630. In ventral tegmental area (VTA) DA neurons from TRPV1 KO mice a transient inhibition of firing by OLDA was observed. Thus OLDA modulates the firing of nigrostriatal DA neurons through interactions with TRPV1, cannabinoid receptors and dopami...
High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakeful... more High activity of the histaminergic neurons in the tuberomammillary (TM) nucleus increases wakefulness, and their firing rate is highest during waking and lowest during rapid eye movement sleep. The TM neurons receive a prominent innervation from sleep-active gamma-aminobutyric acidergic (GABAergic) neurons in the ventrolateral preoptic nucleus, which inhibits them during sleep. They also receive an excitatory input from the orexin- and dynorphin-containing neurons in the lateral hypothalamus, which are critically involved in sleep regulation and whose dysfunction causes narcolepsy. We have used intracellular recordings and immunohistochemistry to study if orexin neurons exert control over the GABAergic inputs to TM neurons in rat hypothalamic slices. Dynorphin suppressed GABAergic inputs and thus disinhibits the TM neurons, acting in concert with orexin to increase the excitability of these neurons. In contrast, both orexin-A and orexin-B markedly increased the frequency of GABAergic potentials, while co-application of orexin and dynorphin produced responses similar to dynorphin alone. Thus, orexins excite TM neurons directly and by disinhibition, gated by dynorphin. These data might explain some of the neuropathology of narcolepsy.
... 16, 15231537. 26. Monti, JM, Pellejero, T., and Jantos, H. (1986) Effects of H ... 69. Mille... more ... 16, 15231537. 26. Monti, JM, Pellejero, T., and Jantos, H. (1986) Effects of H ... 69. Miller, JD, Farber, J., Gatz, P., Roffwarg, H., and German, DC (1983) Activity of mesen-cephalic dopamine and non-dopamine neurons across stages of sleep and walking in the rat. Brain Res. ...
Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippo... more Compound fiber action potentials of stratum radiatum afferents in slices from human and rat hippocampus are shown to be prolonged by 4-aminopyridine (4-AP). This action can explain the enormous increase in synaptic transmitter release caused by 4-AP.
Hippocampal high-frequency (200 Hz, &... more Hippocampal high-frequency (200 Hz, 'ripple') oscillations were recorded in the CA1 area of behaving rats. The histamine H1-receptor antagonist pyrilamine facilitated while the H2-antagonist zolantidine (5 mg/kg i.p) transiently decreased ripple occurrence. Thioperamide, an H3 antagonist, had no effect. The 5-HT1A-receptor antagonist WAY100635 (50 microg i.c.v.) reduced the occurrence and the intrinsic frequency of ripples. The 5-HT3-receptor antagonist Y-25130 (i.c.v.) increased the number but reduced the amplitude of ripples. All the treatments affected sharp-waves and ripple oscillations to the same extent. Changes of ripple occurrence were not secondary to alterations of behavior. In the light of these divergent actions via different receptor subtypes the net effect of aminergic innervations will be determined by their state-dependent activities and mutual interactions as well as receptor localizations.
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Papers by Helmut Haas