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The Journal of Neuroscience, September 10, 2008, 28(37):9111-9116; doi:10.1523/JNEUROSCI.0381-08.2008

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Brief Communications
Presynaptic Type III Neuregulin 1 Is Required for Sustained Enhancement of Hippocampal Transmission by Nicotine and for Axonal Targeting of {alpha}7 Nicotinic Acetylcholine Receptors

Chongbo Zhong,1 Chuang Du,1 Melissa Hancock,2 Marjolijn Mertz,1,4 David A. Talmage,3 and Lorna W. Role1,2

1Department of Neurosciences and 2Integrated Program in Cellular, Molecular, and Biophysical Studies, Columbia University, New York, New York 10032, 3Department of Pharmacology and Center for Brain and Spinal Cord Research, Stony Brook University, Stony Brook, New York 11794, and 4Department of Experimental Neurophysiology, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands

Correspondence should be addressed to Lorna W. Role at her present address: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794. Email: lorna.role{at}stonybrook.edu

Both the neuregulin 1 (Nrg1) and {alpha}7 nicotinic acetylcholine receptor ({alpha}7*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 Nrg1tm1Lwr heterozygote ventral hippocampal slices to wild-type (WT) nucleus accumbens neurons (1) lack a sustained, {alpha}7*nAChRs-mediated phase of synaptic potentiation seen in comparable WT/WT circuits and (2) are deficient in targeting {alpha}7*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.

Key words: neuregulin 1; {alpha}7 nicotinic acetylcholine receptor; sensory–motor gating; ventral hippocampal–nucleus accumbens synapses; schizophrenia; synaptic plasticity

Received Jan. 28, 2008; revised June 30, 2008; accepted July 1, 2008.

Correspondence should be addressed to Lorna W. Role at her present address: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794. Email: lorna.role{at}stonybrook.edu






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