In brain stem slices from neonatal (postnatal days 0-4) CD-1 mice, muscarinic ACh receptors (MAChRs) increased rhythmic inspiratory-related and tonic hypoglossal nerve discharge and depolarized single hypoglossal motoneurons (HMs) via an inward current without changing input resistance. These responses were blocked by the MAChR antagonist 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; 100 nM). MAChRs shifted voltage-dependent activation of the hyperpolarization-activated cation current to more positive levels. MAChRs increased the HM repetitive firing rate and decreased rheobase, with both effects being blocked by 4-DAMP. Muscarinic agonists reduced the afterhyperpolarization of single action potentials (APs), suggesting that small-conductance Ca(2+)-dependent K(+) current inhibition increased the HM firing rate. Muscarinic agonists also reduced the AP amplitude and slowed its time course, suggesting that MAChRs inhibited voltage-gated Na(+) channels. To compare muscarinic excitation of single HMs to muscarinic excitatory effects on motor output in thicker brain stem slices requiring higher extracellular K(+) for rhythmic activity, we tested the effects of muscarinic agonists on single HM excitability in high-K(+) artificial cerebrospinal fluid (aCSF). In high-K(+) aCSF, muscarinic agonists still depolarized HMs and altered AP size and shape, as in standard aCSF, but did not increase the steady-state firing rate, decrease afterhyperpolarization, or alter threshold potential. These results indicate that the basic cellular response of HMs to muscarinic receptors is excitatory, via a number of distinct mechanisms, and that this excitatory response will be largely preserved in rhythmically active brain stem slices.
Ireland, M., Funk, G. D., & Bellingham, M. C. (2012). Muscarinic acetylcholine receptors enhance neonatal mouse hypoglossal motoneuron excitability in vitro. Journal of Applied Physiology, 113(7), 1024-1039. https://doi.org/10.1152/japplphysiol.00699.2011