Neuregulins increase alpha7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus.
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 alpha7 subunit of the nAChR. When the cells were treated with 5 nm neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in (125)I-alpha-bungarotoxin binding. The fast ACh-induced peak current was prominent in large neurons that also contained GABA immunoreactivity. These presumptive GABAergic neurons constituted approximately 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-beta1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1 also increased the percentage of neurons that exhibited ACh-evoked PSCs.
Liu
Y
Y
Section on Developmental Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. liuy@ninds.nih.gov
Ford
B
B
Mann
M A
MA
Fischbach
G D
GD
D000109:Acetylcholine / Q000494:pharmacology; D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002469:Cell Separation; D002478:Cells, Cultured; D018678:Cholinergic Agents / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus; D007395:Interneurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D020890:Neuregulin-1 / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002038:Bungarotoxins; D018678:Cholinergic Agents; C579165:Chrna7 protein, rat; D018691:Excitatory Amino Acid Antagonists; D007457:Iodine Radioisotopes; D020890:Neuregulin-1; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D000109:Acetylcholine; D000157:Aconitine