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J Neurosci. 2008 Nov 26;28(48):12691-9. doi: 10.1523/JNEUROSCI.4166-08.2008.

A neonatal ventral hippocampal lesion causes functional deficits in adult prefrontal cortical interneurons.

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  • 1Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.

Abstract

Animals with a neonatal ventral hippocampal lesion (NVHL) develop abnormal behaviors during or after adolescence, suggesting that early insults can have delayed consequences. Many of these behaviors depend on the prefrontal cortex (PFC), and we have reported that PFC pyramidal neurons of adult rats with an NVHL respond to stimulation of the ventral tegmental area with an increase in firing instead of the characteristic decrease. As the dopamine modulation of cortical interneurons matures during adolescence, these findings raise the possibility that maturation of local inhibitory circuits within the PFC may have been altered in NVHL rats. Here, we assessed the state of PFC interneurons in NVHL rats with in situ hybridization measures of the mRNAs for the calcium binding protein parvalbumin (PV) and the GABA synthesizing enzyme GAD(67), as well as with electrophysiological measures of interneuron function. Although no differences were observed with PV or GAD(67), whole-cell recordings in slices revealed abnormal responses to the D(2) agonist quinpirole in interneurons from NVHL rats. The loss of D(2) modulation of local inhibition in slices from NVHL rats was also evident in the absence of a lasting component in the D(2) attenuation of excitatory synaptic responses in pyramidal neurons, which in sham treated rats was picrotoxin sensitive. The results suggest that the neonatal lesion causes improper maturation, but not loss, of PFC interneurons during adolescence, a finding consistent with current interpretations of imaging data in schizophrenia that suggest a hyperactive, "noisy" cortex underlying dysfunction in the PFC and other cortical areas.

PMID:
19036962
[PubMed - indexed for MEDLINE]
PMCID:
PMC2676938
Free PMC Article

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