MODULATION OF CHOLINERGIC NUCLEUS BASALIS NEURONS BY ACETYLCHOLINE AND N-METHYL-D-ASPARTATE

Known to exert an important modulatory influence on the cerebral corte x, the cholinergic neurons of the basal forebrain are modulated in tur n by neurotransmitters which may include acetylcholine released from p rocesses of brainstem or forebrain neurons. In the present study, we e xamined the effect of carbachol, a non-specific cholinergic agonist, e ither alone or in the presence of N-methyl-D-aspartate upon electrophy siologically identified cholinergic basalis neurons in guinea-pig basa l forebrain slices. Carbachol produced a direct postsynaptic hyperpola rization, accompanied by a decrease in membrane resistance. Muscarine could mimic this hyperpolarizing effect, whereas nicotine produced a d irect postsynaptic membrane depolarization. The interaction of carbach ol with N-methyl-D-aspartate was subsequently tested since, in a prior study, N-methyl-D-aspartate was shown to induce rhythmic bursting in cholinergic cells when they were hyperpolarized by continuous injectio n of outward current. Applied simultaneously with iv-methyl-D-aspartat e in the absence of current injection, carbachol was also found to pro mote rhythmic bursting in half of the cells rested. Since the bursts u nder these conditions were markedly longer in duration than those obse rved in the presence of N-methyl-D-aspartate alone, it was hypothesize d that carbachol might have another action, in addition to the membran e hyperpolarization. Using dissociated cells, it was found that brief applications of carbachol could indeed diminish the slow afterhyperpol arizations that follow single spikes, short bursts or long trains of a ction potentials in cholinergic basalis neurons. These results indicat e that, through its dual ability to hyperpolarize cholinergic neurons and to reduce their afterhyperpolarizations, acetylcholine can promote the occurrence of rhythmic bursting in the presence of N-methyl-D-asp artate. Accordingly, whether derived from brainstem or local sources, acetylcholine may facilitate rhythmic discharge in cholinergic basalis neurons which could in turn impose a rhythmic modulation upon cortica l activity during particular states across the sleep-waking cycle. (C) 1997 IBRO. Published by Elsevier Science Ltd.