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The Substantia Nigra the Tuberomammillary Nucleus

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The Substantia Nigra the Tuberomammillary Nucleus Neurotransmitter Receptors in the Substantia Nigra & the Tuberomammillary Nucleus Coronal Section Coronal Section Coronal Section Substantia Nigra From Pedunculopontine Nucleus Pars Compacta From Dorsal Raphe From Striatum (Caudate/Putamen) Substantia Nigra Hypothalamus Hypothalamus Substantia Nigra From Striatum (Caudate/Putamen) 5-HT R The Substantia Nigra 1B M Muscarinic AChR The substantia nigra (SN) is an area of deeply pigmented cells in the 5 ACh+ midbrain that regulates movement and coordination. Neurons of the nAChR α4α5α6β2 SN are divided into the substantia nigra pars compacta (SNc) and the substantia nigra pars reticulata (SNr). Neurons of the SNc produce Dopamine, which stimulates movement. In contrast, GABAergic neurons of the SNr can stimulate or inhibit movement depending on GABA+ GABAergic Neuron the input signal. GluR6:KA2 D2R mGluR5 mGluR3 From Subthalamic Nucleus GABA-A-R The SN controls movement by functioning as part of the basal ganglia, α3γ2 5-HT1BR Adenosine A1R CB1R a network of neurons that is critical for motion and memory. Along with GABA-B-R1 α GABA+ 4 Astrocyte GABA-B-R2 the SN, the basal ganglia consists of the putamen, the subthalamic EAAT1/GLAST-1 D R + + nAChR α3γ2 1 Neurokinin A /GABA nucleus, the caudate, and the globus pallidus, which is further divided GABA-A-R mGluR7 NK3R NK3R GABA-B-R1 µ-Opioid receptor into the globus pallidus interna (GPi) and the globus pallidus externa EAAT3 GABA-A-R α3γ3/γ2 GABA-B-R2 (GPe). Excluding the caudate, which is thought to be involved in EAAT4 D R learning and memory, the nuclei of the basal ganglia receive signals 2 D R α α β from the cerebral cortex when there is intent to coordinate movement. 5 nAChR 4 5 2 α3∆ TrkB TrkC Signals received by the basal ganglia from the cerebral cortex can be GlyR D R relayed through a direct pathway, which may stimulate movement, 2 GABA-A-R TrkB or an indirect pathway, which may inhibit movement. In the direct To Striatum (Caudate/Putamen) From Globus Pallidus TrkC Adenosine A1R pathway, inhibitory outputs project directly from the putamen to [D1R]2 the SNr or GPi, which transmit inhibitory signals to the thalamus. In D R D1R Dopaminergic Neuron 3 D R response, the thalamus sends excitatory signals back to the cerebral CB1R 2 GABA-B-R2 Substance P+/GABA+ α β γ cortex, which leads to the modulation of motor neurons. In the indirect GluR5/7 1 2 1 GABA-B-R1 GABA-B-R2 NK1R pathway, signals are relayed from the putamen to the GPe prior to GABA-B-R1 GABA-A-R NK1R VGlut2 Glu+ D R 5-HT R GABA+ 1 2C D R reaching the SNr/GPi. The presence of the extra step in the indirect Glu+ mGluR1a 1 mGluR4 mGluR7a D R HR3R pathway reduces thalamic activity, which is thought to downregulate GluR1:2/3 4 D R α1β2γ2 GluR5/7 2 NK3R movement. The combined actions of signals transmitted via the direct NMDA NR1/2B/2D GABA-A-R and indirect pathways are believed to enable fine movement control. D5R Dopamine produced by the SNc and Acetylcholine produced by D3R α α α β cholinergic interneurons affect movement through interactions with κ-Opioid Receptor 4 5 6 2 the direct and indirect pathways. Acetylcholine inhibits movement nAChR by exciting the indirect pathway and inhibiting the direct pathway. In contrast, Dopamine increases movement by stimulating the direct GABAergic Neuron GlyR pathway (Dopamine 1 Receptor-mediated) and inhibiting the CB1R GABAergic Neuron mGluR1 nAChR (α7) indirect pathway (Dopamine 2 Receptor-mediated). Degeneration of 5 GABA-B-R1 Glu+ GluR4 dopaminergic neurons, a hallmark of Parkinson’s disease, leads to a GABA-B-R2 significant reduction in neuronal Dopamine, which reduces excitation mGluR4 NMDA NR1/2B of the direct pathway and increases the activity of the indirect D1R pathway. Thus, the loss of Dopamine causes an imbalance of activity in Pars Reticulata the direct:indirect pathways, which causes a net loss of motor activity To Thalamus and Pedunculopontine Nucleus and a reduction in fine movement control. To Thalamus and Pedunculopontine Nucleus Cerebral Peduncle The Tuberomammillary Nucleus Tuberomammillary Nucleus Located in the posterior hypothalamus, the tuberomammillary nucleus (TMN) is a compact cluster of neurons that serves as the sole source of neuronal Histamine. Although small in size, the TMN regulates several biological processes including thermoregulation, food intake, + Orexin+ Interneuron P2Y1 D R Orexin GluR2/1 neuroendocrine functions, and the sleep-wake cycle. Its role in the Adenosine A R 4 Glut+ 1 α sleep-wake cycle is supported by the observation that TMN activity is 5 µ-Opioid Receptor β 3 GABA-A-R GluR2/4 Dorsolateral Group highest during wakefulness, low during slow wave (deep) sleep, and ATP+ γ GABA+ 2 Substance P+ absent during REM sleep. Activity of TMN neurons is also influenced P2Y4 D2R by inputs from GABA-, Orexin/Glutamate-, and endocannabinoid- D R expressing neurons. 3 EP4 Orexin+ + Histamine, produced by decarboxylation of Histidine, is released at α1 Glut GABA-A-R Dynorphin+ sites that lack classical synapses, appears to diffuse freely, and has β3 + γ NMDA NR1 ATP 1 α no high-affinity uptake mechanism. Extracellularly, Histamine can GABA+ NMDA NR2A GABA-A-R 2 β + 3 GABA be inactivated by neuronal Histamine N-Methyltransferase or it can NMDA NR2B ε bind to Histamine Receptors expressed by nearby neurons. Histamine GHS-R Receptors differ in localization, function, and signaling properties Serotonin+ depending on the receptor subtype. For example, Histamine H1 5-HT R NOP/ORL /KOR-3 2C Receptors (HRH1), HRH2, and HRH3 are expressed in the central 1 nervous system as well as other tissues. In contrast, HRH4 is primarily GlyR expressed in bone marrow and leukocytes. + The number of neurons in the TMN has been estimated to be as low Gly TRHR Histaminergic Neuron as 65,000 in primates and 4,000 in rodents. Neurons in the TMN have D2R CRHR-1 been tentatively divided into five groups, termed E1-E5. These groups, TRH+ HRH3 CRHR-1 either collectively or individually, impact sleep, the stress response, TRHR2 TRHR 1 mGluR1 and appetite. TMN neuron groups E1 and E2 contribute to wakefulness Kir3 P2X2 and food intake whereas the E4 and E5 groups are sensitive to stress ATP+ AChRα7 HRH3 a GABA+ OX2R Orexin+ and induce secretion of Adrenocorticotropic Hormone, -Melanocyte Ventrolateral Group Glu+ Histaminergic/Dopaminergic Neuron Stimulating Hormone, and Prolactin through projections to the Leptin R mGluR5 paraventricular hypothalamus. The function of the E3 group is not yet GABA-B-R TRH+ D R known. 3 NCKX2 KEY: 5-Hydroxytryptamine Receptor (5-HTR) Kainate Receptor Opioid Receptor-like 1/Kappa-type 3 Opioid Receptor (ORL1/KOR) Need neurotransmitter Adenosine A1 Receptor M5 Muscarinic Acetylcholine Receptor Orexin Receptor Type 2 (OXR2) agonists & antagonists? Cannabinoid Receptor 1 (CB1R) Metabotropic Glutamate Receptor (mGluR) Potassium Channel, Inward Rectifying (Kir) Dopamine Receptor (DR) Neurokinin-1 Receptor (NK1R) Prostaglandin E Receptor 4 (EP4) Visit Tocris Bioscience GABA Receptor (GABA-R) Neurokinin-3 Receptor (NK3R) Purinergic Receptor (P2X and P2Y) at Booth #841 Glycine Receptor (GlyR) Nicotinic Acetylcholine Receptor (nAChR) Sodium Calcium Potassium Exchanger 2 (NCKX2) Glutamate Receptor (GluR) NMDA Receptor Thyrotropin Releasing Hormone Receptor (TRHR) Growth Hormone Secretagogue Receptor (GHS-R) k-Opioid Receptor Histamine H3 Receptor (HRH3) m-Opioid Receptor NOTE: This poster conveys a general overview and should be considered neither comprehensive nor definitive. The details of the process are understood to be subject to interpretation. © R&D Systems, Inc. 2012 R&D Systems, Inc., 1-800-343-7475, www.RnDSystems.com PM_07.12_subnigra_411.
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