M. Alkondon et Ex. Albuquerque, Nicotinic acetylcholine receptor alpha 7 and alpha 4 beta 2 subtypes differentially control GABAergic input to CA1 neurons in rat hippocampus, J NEUROPHYS, 86(6), 2001, pp. 3043-3055
The hippocampus, a limbic brain region involved in the encoding and retriev
al of memory, has a well-defined structural network assembled from excitato
ry principal neurons and inhibitory interneurons. Because the GABAergic int
erneurons form synapses onto both pyramidal neurons and interneurons, the a
ctivation of nicotinic acetylcholine receptors (nAChRs) present on certain
interneurons could induce either inhibition or disinhibition in the hippoca
mpal circuitry. To understand the role of nAChRs in controlling synaptic tr
ansmission in the hippocampus, we evaluated the magnitude of nAChR-modulate
d GABAergic postsynaptic currents (PSCs) in pyramidal neurons and various i
nterneurons of the CA1 region. Using whole cell patch-clamp recording and p
ost hoc identification of neuronal types in rat hippocampal slices, we show
that brief (12-s) nAChR activation by ACh (1 mM) or choline (10 mM) enhanc
es the frequency of GABAergic PSCs in both pyramidal neurons and CA1 intern
eurons. The magnitude of alpha7 nAChR-mediated GABAergic inhibition, as ass
essed by the net charge of choline-induced PSCs, was highest in stratum lac
unosum moleculare interneurons followed by pyramidal neurons and s. radiatu
m interneurons. In contrast, the magnitude of alpha4 beta2 nAChR-mediated G
ABAergic inhibition, as assessed by the difference between the net charge o
f PSCs induced by ACh and choline, was highest in pyramidal neurons followe
d by s. lacunosum moleculare and s. radiatum interneurons. The present resu
lts suggest that cholinergic cues transmitted via specific subtypes of nACh
Rs modify the synaptic function in the hippocampus by inducing a differenti
al degree of GABAergic inhibition in the target neurons.