Forebrain gene expression predicts deficits in sensorimotor gating after isolation rearing in male rats.
Compared to socially housed (SH) rats, adult isolation-reared (IR) rats exhibit phenotypes relevant to schizophrenia (SZ), including reduced prepulse inhibition (PPI) of startle. PPI is normally regulated by the medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). We assessed PPI, auditory-evoked local field potentials (LFPs) and expression of seven PPI- and SZ-related genes in the mPFC and NAC, in IR and SH rats. Buffalo (BUF) rats were raised in same-sex groups of 2-3 (SH) or in isolation (IR). PPI was measured early (d53) and later in adulthood (d74); LFPs were measured approximately on d66. Brains were processed for RT-PCR measures of mPFC and NAC expression of Comt, Erbb4, Grid2, Ncam1, Slc1a2, Nrg1 and Reln. Male IR rats exhibited PPI deficits, most pronounced at d53; male and female IR rats had significantly elevated startle magnitude on both test days. Gene expression levels were not significantly altered by IR. PPI levels (d53) were positively correlated with mPFC expression of several genes, and negatively correlated with NAC expression of several genes, in male IR but not SH rats. Late (P90) LFP amplitudes correlated significantly with expression levels of 6/7 mPFC genes in male rats, independent of rearing. After IR that disrupts early adult PPI in male BUF rats, expression levels of PPI- and SZ-associated genes in the mPFC correlate positively with PPI, and levels in the NAC correlate negatively with PPI. These results support the model that specific gene-behavior relationships moderate the impact of early-life experience on SZ-linked behavioral and neurophysiological markers.
Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., La Jolla, CA 92093-0804, USA. Electronic address: nswerdlow@ucsd.edu.
Neal R
NR
Swerdlow
Gregory A
GA
Light
Ryan S
RS
Trim
Michelle R
MR
Breier
Samantha R
SR
Hines
Susan B
SB
Powell
D000161:Acoustic Stimulation; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007794:Lameness, Animal / Q000473:pathology*; D008297:Male; D016548:Prosencephalon / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D000091042:Reelin Protein; D013216:Reflex, Startle; D012934:Social Isolation
Catechol-O-methyltransferase; Isolation rearing; Medial prefrontal cortex; Nucleus accumbens; Prepulse inhibition; Schizophrenia