mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus
Autor: | Vanessa Rupprecht, Yan-Gang Sun, Michael Beierlein, Frederik Seibt, Li Zhou, Rajan Dasgupta |
---|---|
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine Receptor Metabotropic Glutamate 5 Action Potentials Glutamic Acid Biology Neurotransmission Receptors Metabotropic Glutamate Synaptic Transmission Mice 03 medical and health sciences 0302 clinical medicine Postsynaptic potential medicine Animals Cholinergic neuron Mice Knockout Neurotransmitter Agents Ventral Thalamic Nuclei Basal forebrain Thalamic reticular nucleus Neuronal Plasticity General Neuroscience Long-term potentiation Articles Cholinergic Neurons Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Metabotropic glutamate receptor Cholinergic Female Neuroscience 030217 neurology & neurosurgery |
Zdroj: | The Journal of Neuroscience. 36:7886-7896 |
ISSN: | 1529-2401 0270-6474 |
Popis: | 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 Ca2+ 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. SIGNIFICANCE STATEMENT 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. |
Databáze: | OpenAIRE |
Externí odkaz: |