Neuregulins increase alpha 7 nicotinic acetylcholine receptors and enhanceexcitatory synaptic transmission in GABAergic interneurons of the hippocampus

Neuregulins are highly expressed in the CNS, especially in cholinergic neur ons. We have examined the effect of neuregulin on nicotinic acetylcholine r eceptors (nAChRs) in neurons dissociated from the rat hippocampus. Rapid ap plication of acetylcholine (ACh) induced a rapidly rising and decaying inwa rd current in some of the neurons, which was completely blocked by methylly caconitine, 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 twofo ld increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in I-125-alpha -bungarotoxin binding. The f ast ACh-induced peak current was prominent in large neurons that also conta ined GABA immunoreactivity. These presumptive GABAergic neurons constituted similar to 10% of neurons present in 7- to 9-d-old cultures. In addition t o the large inward peak current, ACh also evoked transmitter release from p resynaptic nerve terminals. Pharmacologic experiments indicated that the sh ower 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 increase d the percentage of neurons that exhibited ACh-evoked PSCs.