Enhancing excitatory projections from the ventral subiculum to the nucleus accumbens shell contribute to the MK-801-induced impairment of prepulse inhibition.

Prepulse inhibition (PPI), a measure of sensorimotor gating, has been shown to be disrupted in several animal models of neuropsychiatric disorders, such as schizophrenia. The neural circuits involving the hippocampus and nucleus accumbens (NAC) have been studied in rats to uncover the neurochemical and neuroanatomical substrates that regulate PPI. Majority of the studies of the hippocampus on PPI to date have been focused on CA1, CA2, and dentate gyrus (DG) area. Little is known about the role of the subiculum, which maintains the hippocampal formation intact, on the sensorimotor gating. In this study, the PPI disruption was induced by intraperitoneal injection of MK-801 in rats, and the neuronal activity in the dorsal and ventral subiculum by c-Fos immunostaining was examined. The projections from the subiculum to the nucleus accumbens (NAC) were detected by retrograde tracing of cholera toxin B subunit, in the PPI dysfunctional animals. The results showed an increase in neuronal activity in the ventral subiculum (vSub) while remaining constant in the dorsal subiculum during PPI disruption. The excitatory projections from the vSub to the NAC shell were significantly enhanced when PPI was disrupted. Muscimol Inhibition of vSub could significantly ameliorate the MK801-induced PPI deficit. This data suggests that the enhancement of neuronal activity in the vSub was associated with the PPI impairment, possibly due to the enhanced excitatory output from vSub the NAC shell.

Mice Lacking the Transcriptional Coactivator PGC-1α Exhibit Hyperactivity.

Significant evidence from various sources suggests that structural alterations in mitochondrial function may play a role in both the pathogenesis of mood disorders and the therapeutic effects of available treatments. PGC-1α is a distinct transcriptional regulator designed to mediate the synchronous release of neurotransmitter in the brain and thereby to coordinate a number of gene expression pathways to promote mitochondrial biogenesis and oxidative phosphorylation. The role of PGC-1α in the context of affective disorder phenotypes and treatments has been suggested but not studied in depth. To further investigate the possible involvement of PGC-1α in affective disorders, we generated conditional PGC-1α null mice through transgenic expression of cre recombinase under the control of a Dlx5/6 promoter; cre-mediated excision events were limited to γ-amino-butyric-acid (GABA)-ergic specific neurons. We tested these mice in a battery of behavioral tests related to affective change including spontaneous activity, elevated plus maze, forced swim test, and tail suspension test. Results demonstrated that mice lacking PGC-1α in GABAergic neurons exhibited increased activity across tests that might be related to a mania-like phenotype. These results suggest possible relevance of PGC-1α to affective change, which corresponds with data connecting mitochondrial function and affective disorders and their treatment.