Av. Buhler et Tv. Dunwiddie, Regulation of the activity of hippocampal stratum oriens interneurons by alpha 7 nicotinic acetylcholine receptors, NEUROSCIENC, 106(1), 2001, pp. 55-67
GABAergic interneurons have been shown to be a major target of cholinergic
inputs to the hippocampus. Because these interneurons project to pyramidal
neurons as well as other interneurons, activation of the cholinergic system
is likely to produce a complex modulation of local inhibitory activity. To
better understand the role of postsynaptic alpha7 nicotinic acetylcholine
receptors in the hippocampus, we have characterized the effects of nicotini
c agents on local interneurons of the rat CAI stratum oriens in terms of ac
tivation, desensitization, and region of axonal termination. Fast applicati
on of acetylcholine onto stratum oriens interneurons during whole-cell reco
rdings from hippocampal slices activated the majority of cells tested, and
these responses were mediated almost entirely by alpha7 nicotinic acetylcho
line receptors. Anatomical reconstructions showed no clear relationship bet
ween the acetylcholine responsivity of interneurons and the regions to whic
h their axons project. Currents mediated by a7 receptors declined markedly
during repetitive activation in the theta rhythm range (4-12 Hz) when activ
ated by either pressure application or synaptic release of acetylcholine. H
owever, the decay of alpha7 receptor-mediated currents was unaffected by tr
eatment with the cholinesterase, inhibitor neostigmine (10 nM-10 muM), sugg
esting that hydrolysis of acetylcholine is not a rate-limiting step in the
termination of these responses.
From these findings we suggest that nicotinic receptor activity in this reg
ion has an extensive and complex impact on local inhibitory circuits that i
s mediated by activation of several classes of intrinsic GABAergic cells. I
n addition, desensitization of the a7 nicotinic acetylcholine receptor is l
ikely to contribute to the decay of individual responses to pressure applic
ation of agonist, and may also act in a cumulative fashion to impair the ab
ility of these receptors to support repetitive activity during trains of ac
tivation. If applicable to alpha7 receptor responses in vivo, we suggest it
may be difficult to enhance these responses for therapeutic purposes with
cholinesterase inhibitors. (C) 2001 IBRO. Published by Elsevier Science Ltd
. All rights reserved.