Award: Woodrow Wilson
Targeting hippocampal dysfunction improves cognition in a schizophrenia model
Recent clinical studies using neuroimaging and preclinical models of schizophrenia indicate that aberrant hippocampal excitability may contribute to cognitive impairment and augment psychotic symptoms due to disinhibition of dopaminergic neurons. Treatments with compounds targeting hippocampal overactivity to normalize this condition might improve hippocampal-dependent memory and reduce dopamine hyperactiviation via functional pathways connecting the hippocampus and the ventral tegmental area. Here, we tested this therapeutic approach to assess both cognitive impairment and a potential benefit on other symptoms of schizophrenia associated with dopamine dysregulation. In a well-established ketamine model, we tested rats for their hippocampal-dependent memory performance on a radial maze task, and for their dopamine responsiveness with an amphetamine challenge with the antiepileptic medication, levetiracetam, which mediates its effect via synaptic vesicle glycoprotein 2A (SV2A) that primes vesicles for activity-dependent transmitter release.
Mentor: Drs. Michela Gallagher & Ming Teng Koh, Department of Psychology & Brain Sciences