Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors. Bellingham, Mark C. and Albert J. Berger. Department of Physiology and Biophysics, University of Washington School of Medicine, Box 357290, Seattle, WA USA 98195-7290.
APStracts 3:0180N, 1996.
1. Whole cell recordings of glutamatergic excitatory postsynaptic currents (EPSCs), evoked by electrical stimulation in the reticular formation, were made from visualized hypoglossal motoneurons (HMs) in rat brainstem slices. 2. Carbachol, muscarine or physostigmine reduced EPSC amplitude to 50? +/-? 3%, 37? +/-? 3% and 54? +/-? 7% (mean +/- SE) of control respectively; effects of carbachol and physostigmine were antagonized by atropine (1-2? [mu]M). EPSC depression was most effectively antagonized by methoctramine, a M2 muscarinic acetylcholine receptor (mAChR) antagonist with a high affinity constant (pKB) of 8.07 for the receptor mediating this response, while pirenzepine, a M1 mAChR antagonist, had a pKB of < 7.0, showing that EPSC depression was mediated by the M2 mAChR. 3. Postsynaptic properties of HMs (holding current, input resistance), EPSCs (reversal potential, rise time, half-width and decay time constant) and postsynaptic glutamate-gated currents (amplitude, waveform) were not altered by carbachol or muscarine. 4. Muscarine did not decrease presynaptic neuron excitability, as the frequency of spontaneous EPSCs in HMs in the absence of TTX was either unchanged or increased. Leak and action currents of reticular formation neurons were not significantly altered by muscarine. In contrast, with TTX present, the frequency of spontaneous miniature glutamatergic EPSCs in HMs was decreased by both carbachol (mean change? =? 203? +/-? 46%) and muscarine (mean? change? =? 185? +/-? 26%), without changing miniature EPSC amplitude distribution. 5. Muscarinic depression of excitatory transmission to HMs thus occurs at the presynaptic terminal, most probably affecting release mechanisms down-stream from calcium entry, and is likely to be significant during rapid-eye-movement sleep, possibly underlying the loss of tongue tone and inspiratory activity during this state.

Received 5 June 1996; accepted in final form 14 August 1996.
APS Manuscript Number J450-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996