Modulation of extrasynaptic GABA_A alpha 5 receptors in the ventral hippocampus normalizes physiological and behavioral deficits in a circuit specific manner.

ABSTRACT: Hippocampal hyperactivity is correlated with psychosis in schizophrenia patients and likely attributable to deficits in GABAergic signaling. Here we attempt to reverse this deficit by overexpression of the α5-GABA_A receptor within the ventral hippocampus (vHipp). Indeed, this is sufficient to normalize vHipp activity and downstream alterations in dopamine neuron function in the MAM rodent model. This approach also attenuated behavioral deficits in cognitive flexibility. To understand the specific pathways that mediate these effects, we used chemogenetics to manipulate discrete projections from the vHipp to the nucleus accumbens (NAc) or prefrontal cortex (mPFC). We found that inhibition of the vHipp-NAc, but not the vHipp-mPFC pathway, normalized aberrant dopamine neuron activit

SUBMITTER: Donegan JJ 

PROVIDER: S-EPMC6597724 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature