Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors.
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.
Zhong
Chongbo
C
Department of Neurosciences, Columbia University, New York, New York 10032, USA.
Du
Chuang
C
Hancock
Melissa
M
Mertz
Marjolijn
M
Talmage
David A
DA
Role
Lorna W
LW
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020880:Neuregulins; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D020880:Neuregulins; D018722:Nicotinic Agonists; C108113:Nrg3 protein, mouse; D011500:Protein Synthesis Inhibitors; D011978:Receptors, Nicotinic; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D064569:alpha7 Nicotinic Acetylcholine Receptor; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D003513:Cycloheximide; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
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