Heterogeneous HPC changes alter context processing in MAM model of schizophrenia

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Heterogeneous HPC changes alter context processing in MAM model of schizophrenia The primary goal of the proposed experiments is to establish a link between ventral hippocampal pathology, e.g. aberrant gating of afferent inputs arising from the basolateral amygdala, and pattern separation deficits in the methylazoxymethanol acetate neurodevelopmental model of schizophrenia. The planned studies involve a combination of in vivo extracellular electrophysiological recording techniques and optogenetic manipulations of specific neural pathways in awake behaving animals, both powerful procedures for the dissection of patterns of neural activation in specific neural circuits and their impact on pathological behaviors. In brief, the extracellular electrophysiological properties of the intrahippocampal, in CA3 and CA1 subregions, dysfunction resulting from MAM treatment will be measured. Specifically, alterations in the gating, and synaptic plasticity, of emotional context input from the basolateral nucleus of the amygdala (BLA) with processed sensory input from entorhinal cortex (EC) will be tested in pyramidal neurons of the CA1 and CA3 subregions of the ventral hippocampus (vHPC) in the MAM rat. In addition, the impact of optogenetic alterations of the BLA-CA3 circuitry on pattern separation, or spatial context discrimination, performance in the MAM rat, a cognitive dimension known to be impaired in schizophrenia, will be evaluated. In normal rats, inactivation of the BLA projections will determine whether this circuitry is required for performance of the spatial context discrimination task following fear conditioning. It is hypothesized that subregional specific, destabilization of afferent input arising from the BLA and EC in CA3 vs CA1 subregions of the vHPC, underlies a deficit in pattern separation performance in MAM rats. There are important implications of the intended studies in regards to the efficacy of pharmacotherapies in the treatment of cognitive impairments schizophrenia. The heterogeneous alteration of vHPC function along with the pattern of context deficits in the MAM rat substantiates the necessity of more targeted pharmacological treatments.