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Journal of Neuroscience, Vol 11, 2588-2597, Copyright © 1991 by Society for Neuroscience
Existence of different subtypes of nicotinic acetylcholine receptors in the rat habenulo-interpeduncular system
C Mulle, C Vidal, P Benoit and JP Changeux
UA CNRS D1284 "Neurobiologie Moleculaire," Departement des Biotechnologies, Institut Pasteur, Paris.
Neuronal nicotinic ACh receptors (nAChRs) are present in the rat medial
habenula (MHB) and interpeduncular nucleus (IPN), two brain regions
connected through the fasciculus retroflexus (FR). The goal of the present
study was to compare the electrophysiological and pharmacological
characteristics of nAChRs located at pre- and postsynaptic sites within the
MHB-IPN system. nAChRs located on the soma of IPN neurons were studied
using patch-clamp techniques and a preparation of acutely isolated neurons.
Whole-cell currents evoked by Ach and nicotine showed an intense
rectification at positive membrane potentials. nAChR channels were
relatively nonselective for cations, had a unitary conductance of 35 pS,
and were activated by several nicotinic agonists with the following rank
order: cytisine greater than ACh greater than nicotine greater than
dimethylphenylpiperazinium (DMPP). They were blocked by mecamylamine,
hexamethonium, curare, and dihydro-beta-erythroidine (DHBE), but were
insensitive to alpha- bungarotoxin and neuronal bungarotoxin. In contrast,
nAChRs recorded on the soma of MHB neurons under equivalent experimental
conditions exhibited different characteristics for single-channel
conductance and agonist and antagonist sensitivity. The pharmacological
properties of presynaptic nAChRs in the IPN were analyzed in a rat brain
slice preparation. Stimulation of the FR produced a presynaptic afferent
volley recorded in the rostral subnucleus of the IPN. Nicotinic agonists
decreased the amplitude of the afferent volley with different efficacies:
nicotine greater than cytisine greater than ACh greater than DMPP. The
action of nicotine was insensitive to alpha-bungarotoxin and to neuronal
bungarotoxin, but was blocked by mecamylamine, hexamethonium, curare, and
DHBE, with IC50 values different from those reported for IPN postsynaptic
nAChRs. This study thus demonstrates the functional diversity of nAChRs in
the rat CNS.
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