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The Journal of Neuroscience, August 1, 2001, 21(15):5660-5669
Neuregulins Increase  7 Nicotinic Acetylcholine Receptors and
Enhance Excitatory Synaptic Transmission in GABAergic Interneurons of
the Hippocampus
Yun
Liu,
Byron
Ford,
Mary Anne
Mann, and
Gerald D.
Fischbach
Section on Developmental Neurobiology, National Institute of Mental
Health, National Institutes of Health, Bethesda, Maryland 20892
Neuregulins are highly expressed in the CNS, especially in
cholinergic neurons. We have examined the effect of neuregulin on
nicotinic acetylcholine receptors (nAChRs) in neurons dissociated from
the rat hippocampus. Rapid application of acetylcholine (ACh) induced a
rapidly rising and decaying inward current in some of the neurons,
which was completely blocked by methyllycaconitine, a specific
antagonist of the  7 subunit of the nAChR. When the cells were
treated with 5 nM neuregulin (NRG1- 1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was
observed, and there was a comparable increase in
125I--bungarotoxin binding. The fast ACh-induced peak
current was prominent in large neurons that also contained GABA
immunoreactivity. These presumptive GABAergic neurons constituted
~10% of neurons present in 7- to 9-d-old cultures. In addition to
the large inward peak current, ACh also evoked transmitter release from
presynaptic nerve terminals. Pharmacologic experiments indicated that
the shower of PSCs was mediated by glutamate, with a small minority caused by the action of GABA. Chronic exposure to NRG1-1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC.
NRG1-1 also increased the percentage of neurons that exhibited ACh-evoked PSCs.
Key words:
neuregulin; nicotinic acetylcholine receptors; hippocampus; -bungarotoxin; GABAergic interneurons; synaptic
transmission
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155660-10$05.00/0
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