Adolescent isolation rearing produces a prepulse inhibition deficit correlated with expression of the NMDA GluN1 subunit in the nucleus accumbens
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Adolescence is a transition period during which social interaction is necessary for normal brain and behavior development. Severely abnormal social interactions during adolescence can increase the incidence of lifelong psychiatric disease. Decreased prepulse inhibition (PPI) is a quantifiable hallmark of some psychiatric illnesses in humans and can be elicited in rodents by isolation rearing throughout the adolescent transition period. PPI is a measure of sensorimotor gating in which the nucleus accumbens (Acb) is crucially involved. The Acb is comprised of core and shell subregions, which receive convergent dopaminergic and glutamatergic inputs. To gain insight into the neurobiological correlates of adolescent adversity, we conducted electron microscopic immunolabeling of dopamine D1 receptors (D1Rs) and the GluN1 subunit of glutamate NMDA receptors in the Acb of isolation-reared (IR) adult male rats. In all animals, GluN1 was primarily located in dendritic profiles, many of which also contained D1Rs. GluN1 was also observed in perisynaptic glia and axon terminals. In IR rats compared with group-reared controls, GluN1 density was selectively decreased in D1R-containing dendrites of the Acb core. Across all animals, dendritic GluN1 density correlated with average percent PPI, implicating endogenous expression of NMDA receptors of the Acb as a possible substrate of the PPI response. These results suggest that adolescent isolation dampens NMDA-mediated excitation in direct (D1R-containing) output neurons of the Acb, and that these changes influence the operational measure of PPI.
KeywordsNMDA receptor D1 receptor Sensorimotor gating Social isolation Adolescence Electron microscopy
The authors gratefully acknowledge the receipt of National Institute of Drug Abuse funding on Grants T32DA7274 to MLF and DA004600 to VMP, and National Institute of Mental Health funding on Grants T32MH15144 to MLF and MH40342 to VMP.
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Conflict of interest
The authors declare that they have no conflicts of interest.
This article does not contain any studies with human participants performed by any of the authors. All procedures involving animals were carried out in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals, and were approved by the Institutional Animal Care and Use Committees (IACUC) at Weill-Cornell Medical College. Every effort was made to minimize the number of animals used and their suffering.
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