A direct nicotinic receptor-mediated inhibition recorded intracellularly in vitro

Abstract

ACETYLCHOLINE activates both nicotinic and muscarinic receptors in the central nervous system¹. Although the action of acetylcholine at muscarinic receptors has been well characterized, relatively little is known at the cellular level concerning nicotinic receptor stimulation in brain. Central nicotinic receptors have been implicated in Alzheimer's disease², seizure activity³, the generation of slow-wave theta rhythm in the hippocampus⁴ and the potential abuse liability of nicotine⁵. At the neuronal level, nicotinic agonists have been most often associated with postsynaptically mediated excitation and membrane depolarization at various sites, including Renshaw spinal motoneurons⁶, locus coeruleus⁷ and the medial habenular nucleus⁸. Nicotine acting presynaptically can produce either excitation or inhibition indirectly through the release of endogeneous transmitters or modulators^9–12. Whereas a direct inhibitory effect of nicotine has been suggested by one in vivo extracellular recording study in rat cerebellar Purkinje neurons¹³, the mechanism(s) underlying this action is not yet known. We now report our findings obtained using in vitro intracellular methods in a submerged brain slice preparation in which application of nicotinic agonists to rat dorsolateral septal neurons reveal a direct membrane hyperpolarization mediated by an increase in potassium conductance.