title: mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus.
abstract: Acetylcholine (ACh) signaling is involved in a wide range of processes, including arousal, attention, and learning. An increasing number of studies indicate that cholinergic control of these functions is highly deterministic, mediated by synaptic afferents that generate reliable and precise responses in postsynaptic neurons. However, mechanisms that govern plastic changes of cholinergic synaptic strength are poorly understood, even though they are likely critical in shaping the impact of cholinergic inputs on neuronal networks. We have recently shown that in the thalamic reticular nucleus (TRN), synaptic release of ACh generates excitatory-inhibitory biphasic postsynaptic responses, mediated by the activation of α4β2 nicotinic (nAChRs) and M2 muscarinic receptors (mAChRs), respectively. Here, using voltage-clamp recordings from TRN neurons in thalamocortical slices of mice, we demonstrate that the activation of Group I metabotropic glutamate receptors (mGluRs) by ambient or synaptically released glutamate evokes transient increases of nicotinic EPSCs. Additionally, we find that the selective Group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine] evokes long-term potentiation of nicotinic EPSCs (mGluR-nLTP), dependent on increases in postsynaptic Ca(2+) concentration and the activation of phospholipase C. Both the induction and the maintenance of mGluR-nLTP require synergistic activation of mGluR1 and mGluR5. Together, our results show that postsynaptic Group I mGluRs are critically involved in the regulation of cholinergic synaptic strength on different time scales, suggesting that cholinergic control of local thalamic circuits is highly context-dependent and regulated by the overall levels of glutamatergic afferent activity.
  
  
  
  Cholinergic signaling controls information processing and plasticity in neuronal circuits, but the mechanisms underlying the regulation of cholinergic synaptic strength on different time scales are unknown. Here we identify mGluR1 and mGluR5 as key elements in the dynamic regulation of cholinergic synaptic inputs onto neurons of the TRN. Our findings highlight potential mechanisms that regulate cholinergic signaling in the mammalian brain.
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yan-Gang
authors.identifier: 0000-0003-0768-7733
authors.initials: YG
authors.lastname: Sun
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030.
authors.forename: Vanessa
authors.identifier: 0000-0003-1374-8184
authors.initials: V
authors.lastname: Rupprecht
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, Graduate School, University of Chinese Academy of Sciences, Shanghai 200031, China, and.
authors.forename: Li
authors.identifier: 0000-0002-8170-4549
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030.
authors.forename: Rajan
authors.identifier: 0000-0003-0996-4693
authors.initials: R
authors.lastname: Dasgupta
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030.
authors.forename: Frederik
authors.identifier: 0000-0003-0536-5212
authors.initials: F
authors.lastname: Seibt
authors.affiliation: Department of Neurobiology and Anatomy, McGovern Medical School, Houston, Texas 77030, University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas 77030 michael.beierlein@uth.tmc.edu.
authors.forename: Michael
authors.identifier: 0000-0003-2210-3118
authors.initials: M
authors.lastname: Beierlein
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D059329:Cholinergic Neurons / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D020651:Ventral Thalamic Nuclei / Q000502:physiology*
chemical_list: C578936:Grm5 protein, mouse; D018377:Neurotransmitter Agents; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid
keywords: acetylcholine; basal forebrain; long-term plasticity; metabotropic glutamate receptor; synergistic; thalamic reticular nucleus