Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission.
Neurons situated in the principal sensory trigeminal nucleus (PSTN) convey orofacial sensory inputs to thalamic relay regions and higher brain centres, and the excitability of these ascending tract cells is modulated across sleep/wakefulness states and during pain conditions. Moreover, acetylcholine release changes profoundly across sleep/wakefulness states and ascending sensory neurotransmission is altered by cholinergic agonists. An intriguing possibility is, therefore, that cholinergic mechanisms mediate such state-dependent modulation of PSTN tract neurons. We tested the hypotheses that cholinergic agonists can modulate PSTN cell excitability and that such effects are mediated by muscarinic receptor subtypes, using patch-clamp methods in rat and mouse. In all examined cells, carbachol elicited an electrophysiological response that was independent of action potential generation as it persisted in the presence of tetrodotoxin. Responses were of three types: depolarization, hyperpolarization or a biphasic response consisting of hyperpolarization followed by depolarization. In voltage-clamp mode, carbachol evoked corresponding inward, outward or biphasic currents. Moreover, immunostaining for the vesicle-associated choline transporter showed cholinergic innervation of the PSTN. Using muscarinic receptor antagonists, we found that carbachol-elicited PSTN neuron hyperpolarization was mediated by M2 receptors and depolarization, in large part, by M1 receptors. These data suggest that acetylcholine acting on M1 and M2 receptors may contribute to selective excitability enhancement or depression in individual, rostrally projecting sensory neurons. Such selective gating effects via cholinergic input may play a functional role in modulation of ascending sensory transmission, including across behavioral states typified by distinct cholinergic tone, e.g. sleep/wakefulness arousal levels or neuropathic pain conditions.
Kohlmeier
Kristi A
KA
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. Kristi_Kohlmeier@nymc.edu
Soja
Peter J
PJ
Kristensen
Morten P
MP
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000378:metabolism; D002217:Carbachol / Q000378:metabolism; D018679:Cholinergic Agonists / Q000378:metabolism; D015640:Ion Channel Gating; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009538:Nicotine / Q000378:metabolism; D018722:Nicotinic Agonists / Q000378:metabolism; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013779:Tetrodotoxin / Q000378:metabolism; D014278:Trigeminal Nuclei / Q000166:cytology*
D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D018722:Nicotinic Agonists; D020033:Protein Isoforms; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D013779:Tetrodotoxin; D009538:Nicotine; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine