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Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors.


ABSTRACT: Both the neuregulin 1 (Nrg1) and alpha7 nicotinic acetylcholine receptor (alpha7*nAChRs) genes have been linked to schizophrenia and associated sensory-motor gating deficits. The prominence of nicotine addiction in schizophrenic patients is reflected in the normalization of gating deficits by nicotine self-administration. To assess the role of presynaptic type III Nrg1 at hippocampal-accumbens synapses, an important relay in sensory-motor gating, we developed a specialized preparation of chimeric circuits in vitro. Synaptic relays from Nrg1(tm1Lwr) heterozygote ventral hippocampal slices to wild-type (WT) nucleus accumbens neurons (1) lack a sustained, alpha7*nAChRs-mediated phase of synaptic potentiation seen in comparable WT/WT circuits and (2) are deficient in targeting alpha7*nAChRs to presynaptic sites. Thus, selective alteration of the level of presynaptic type III Nrg1 dramatically affects the modulation of glutamatergic transmission at ventral hippocampal to nucleus accumbens synapses.

SUBMITTER: Zhong C 

PROVIDER: S-EPMC2754770 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors.

Zhong Chongbo C   Du Chuang C   Hancock Melissa M   Mertz Marjolijn M   Talmage David A DA   Role Lorna W LW  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20080901 37


Both the neuregulin 1 (Nrg1) and alpha7 nicotinic acetylcholine receptor (alpha7*nAChRs) genes have been linked to schizophrenia and associated sensory-motor gating deficits. The prominence of nicotine addiction in schizophrenic patients is reflected in the normalization of gating deficits by nicotine self-administration. To assess the role of presynaptic type III Nrg1 at hippocampal-accumbens synapses, an important relay in sensory-motor gating, we developed a specialized preparation of chimeri  ...[more]

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