PRESYNAPTIC DEPRESSION OF EXCITATORY SYNAPTIC INPUTS TO RAT HYPOGLOSSAL MOTONEURONS BY MUSCARINIC M2 RECEPTORS

1. Whole cell recordings of glutamatergic excitatory postsynaptic curr ents (EPSCs) evoked by electrical stimulation in the reticular formati on were made from visualized hypoglossal motoneurons (HMs) in rat brai n stem slices. 2. Carbachol, muscarine, or physostigmine reduced EPSC amplitude to 50 +/- 3%, 37 +/- 3%, and 54 +/- 7% (mean +/- SE) of cont rol, respectively; effects of carbachol and physostigmine were antagon ized by atropine (1-2 mu M). EPSC depression was most effectively anta gonized by methoctramine, an M2 muscarinic acetylcholine receptor (mAC hR) antagonist with a high affinity constant (pK(B)) of 8.07 for the r eceptor mediating this response, whereas pirenzepine, an M1 mAChR anta gonist, had a pK(B) of <7.0, showing that EPSC depression was mediated by the M2 mAChR. 3. Postsynaptic properties of HMs (holding current a nd input resistance), EPSCs (reversal potential, rise time, half-width , and decay time constant), and postsynaptic glutamate-gated currents (amplitude and waveform) were not altered by carbachol or muscarine. 4 . Muscarine did not decrease presynaptic neuron excitability, because the frequency of spontaneous EPSCs in HMs in the absence of tetrodotox in (TTX) was either unchanged or increased. Leak and action currents o f reticular formation neurons were not significantly altered by muscar ine. In contrast, with TTX present, the frequency of spontaneous minia ture glutamatergic EPSCs in HMs was decreased by both carbachol (mean change = 203 +/- 46%) and muscarine (mean change = 185 I 26%),with no change in miniature EPSC amplitude distribution. 5. Muscarinic depress ion of excitatory transmission to HMs thus occurs at the presynaptic t erminal, most probably affecting release mechanisms downstream from ca lcium entry, and is likely to be significant during rapid eye movement sleep, possibly underlying the loss of tongue tone and inspiratory ac tivity during this state.