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Muscarinic receptor subtypes differentially control synaptic input and excitability of cerebellum‐projecting medial vestibular nucleus neurons
Author(s) -
Zhu Yun,
Chen ShaoRui,
Pan HuiLin
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13554
Subject(s) - medial vestibular nucleus , neuroscience , vestibular nuclei , oxotremorine , excitatory postsynaptic potential , cerebellum , glutamatergic , vestibular system , muscarinic acetylcholine receptor , inhibitory postsynaptic potential , biology , chemistry , glutamate receptor , receptor , biochemistry
Abstract Neurons in the vestibular nuclei have a vital function in balance maintenance, gaze stabilization, and posture. Although muscarinic acetylcholine receptors ( mAChR s) are expressed and involved in regulating vestibular function, it remains unclear how individual mAChR subtypes regulate vestibular neuronal activity. In this study, we determined which specific subtypes of mAChR s control synaptic input and excitability of medial vestibular nucleus ( MVN ) neurons that project to the cerebellum. Cerebellum‐projecting MVN neurons were labeled by a fluorescent retrograde tracer and then identified in rat brainstem slices. Quantitative PCR analysis suggested that M2 and M3 were the possible major mAChR subtypes expressed in the MVN . The mAChR agonist oxotremorine‐M significantly reduced the amplitude of glutamatergic excitatory post‐synaptic currents evoked by stimulation of vestibular primary afferents, and this effect was abolished by the M2‐preferring antagonist AF ‐ DX 116. However, oxotremorine‐M had no effect on GABA ‐mediated spontaneous inhibitory post‐synaptic currents of labeled MVN neurons. Furthermore, oxotremorine‐M significantly increased the firing activity of labeled MVN neurons, and this effect was blocked by the M3‐preferring antagonist J104129 in most neurons tested. In addition, AF ‐ DX 116 reduced the onset latency and prolonged the excitatory effect of oxotremorine‐M on the firing activity of labeled MVN neurons. Our findings suggest that M3 is the predominant post‐synaptic mAChR involved in muscarinic excitation of cerebellum‐projecting MVN neurons. Pre‐synaptic M2 mAChR regulates excitatory glutamatergic input from vestibular primary afferents, which in turn influences the excitability of cerebellum‐projecting MVN neurons. This new information has important therapeutic implications for treating vestibular disorders with mAChR subtype‐selective agents.Medial vestibular nucleus (MVN) neurons projecting to the cerebellum are involved in balance control. We found that activation of pre‐synaptic M2 muscarinic receptors inhibit glutamatergic input from vestibular primary afferents, whereas stimulation of post‐synaptic M3 muscarinic receptors increases the firing activity of cerebellum‐projecting MVN neurons. This new information advances our understanding of the cholinergic mechanism regulating the vestibular system.