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Coupling of gene expression in medial prefrontal cortex and nucleus accumbens after neonatal ventral hippocampal lesions accompanies deficits in sensorimotor gating and auditory processing in rats.

Abstract：

BACKGROUND:After neonatal ventral hippocampal lesions (NVHLs), adult rats exhibit evidence of neural processing deficits relevant to schizophrenia, including reduced prepulse inhibition (PPI) of acoustic startle and impaired sensory processing. In intact rats, the regulation of PPI by the ventral hippocampus (VH) is mediated via interactions with medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). We assessed PPI, auditory-evoked responses and expression of 7 schizophrenia-related genes in mPFC and NAC, in adult rats after sham- or real NVHLs. METHODS:Male inbred Buffalo (BUF) rat pups (d7; n=36) received either vehicle or ibotenic acid infusion into the VH. PPI and auditory-evoked dentate gyrus local field potentials (LFPs) were measured on d56 and d66, respectively. Brains were processed for RT-PCR measures of mPFC and NAC Comt, Erbb4, Grid2, Ncam1, Slc1a2, Nrg1 and Reln. RESULTS:NVHL rats exhibited significant deficits in PPI (p=0.005) and LFPs (p<0.015) proportional to lesion size. Sham vs. NVHL rats did not differ in gene expression levels in mPFC or NAC. As we previously reported, multiple gene expression levels were highly correlated within- (mean r's≈0.5), but not across-brain regions (mean r's≈0). However, for three genes--Comt, Slc1a2 and Ncam1--after NVHLs, expression levels became significantly correlated, or "coupled," across the mPFC and NAC (p's<0.03, 0.002 and 0.05, respectively), and the degree of "coupling" increased with VH lesion size. CONCLUSIONS:After NVHLs that disrupt PPI and auditory processing, specific gene expression levels suggest an abnormal functional coupling of the mPFC and NAC. This model of VH-mPFC-NAC network dysfunction after NVHLs may have implications for understanding the neural basis for PPI- and related sensory processing deficits in schizophrenia patients.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Swerdlow NR,Powell SB,Breier MR,Hines SR,Light GA

doi

10.1016/j.neuropharm.2013.06.003

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

38-46

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(13)00263-3

journal_volume

pub_type

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Coupling of gene expression in medial prefrontal cortex and nucleus accumbens after neonatal ventral hippocampal lesions accompanies deficits in sensorimotor gating and auditory processing in rats.