Sub-circuit alterations in dorsal hippocampus structure and function after global neurodevelopmental insult

Patients with neuropsychiatric and neurological disorders often express limbic circuit abnormalities and deficits in information processing. While these disorders appear to have diverse etiologies, their common features suggest neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and pruning, to name a few. The precise timing of the neurodevelopmental insult to these processes likely determines the resulting functional outcome. We used the epilepsy and schizophrenia-related gestational day 17 methylazoxymethanol acetate model to examine the impact of this timed neurodevelopmental insult on principal cell morphology and synaptic network function of the dorsal hippocampus (dHPC) circuit. Our observed structural and functional alterations in dHPC are compartment specific, indicating that adverse global exposure during gestation can produce specific alterations and distort information processing in neural circuits that underlie cognitive abilities.