title: Nicotinic receptor-mediated biphasic effect on neuronal excitability in chick lateral spiriform neurons.
abstract: Local neuronal circuits integrate synaptic information with different excitatory or inhibitory time windows. Here we report that activation of nicotinic acetylcholine receptors (nAChRs) leads to biphasic effects on excitability in chick lateral spiriform (SPL) neurons during whole cell recordings in brain slices. Carbachol (100 microM in the presence of 1 microM atropine) produced an initial short-term increase in the firing rates of SPL neurons (125+/-14% of control) that was mediated by postsynaptic nAChRs. However, after 3 min exposure to nicotinic agonists, the firing rate measured during an 800 ms depolarizing pulse declined to 19+/-7% (100 microM carbachol) or 26+/-8% (10 microM nicotine) of the control rate and remained decreased for 10-20 min after washout of the agonists. Similarly, after 60 s of electrically-stimulated release of endogenous acetylcholine (ACh) from cholinergic afferent fibers, there was a marked reduction (45+/-5% of control) in firing rates in SPL neurons. All of these effects were blocked by the nAChR antagonist dihydro-beta-erythroidine (30 microM). The inhibitory effect was not observed in Ca(2+)-free buffer. The nAChR-mediated inhibition depended on active G-proteins in SPL neurons and was prevented by the GABA(B) receptor antagonist phaclofen (200 microM), while the GABA(B) receptor agonist baclofen (10 microM) decreased firing rate in SPL neurons to 13+/-1% of control. The inhibitory response thus appears to be due to a nAChR-mediated enhancement of presynaptic GABA release, which then activates postsynaptic GABA(B) receptors. In conclusion, activation of nAChRs in the SPL initiates a limited time window for an excitatory period, after which a prolonged inhibitory effect turns off this window. The prolonged inhibitory effect may serve to protect SPL neurons from excessive excitation.
authors: Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, 2300 Eye Street, Northwest, Washington, DC 20037, USA. yliu@usuhs.mil
authors: Y-B
authors: YB
authors: Liu
authors: J-Z
authors: JZ
authors: Guo
authors: V A
authors: VA
authors: Chiappinelli
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000166:cytology* / Q000196:embryology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D013997:Time Factors
chemical_list: D018679:Cholinergic Agonists; D018756:GABA Antagonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C052329:phaclofen; D009538:Nicotine; D002217:Carbachol; D001418:Baclofen; D002118:Calcium
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