Behavioral assessments and differential excitability, oscillatory dynamics in dorsal and ventral hippocampal CA1 neurons in male rats of a prenatal VPA-exposed autism model

The distinct electrophysiological properties of the dorsal (dHPC) and ventral (vHPC) hippocampus play crucial roles in cognitive and emotional processing. This study investigates the variations in firing activities between these hippocampal regions to develop targeted therapies for conditions such as autism. We conducted behavioral assessments and explored the properties of CA1 pyramidal neurons in the dHPC and vHPC using whole-cell patch-clamp recordings in a prenatal Valproic Acid (VPA)-exposed autistic-like model. Additionally, oscillatory activities in the dHPC and vHPC were analyzed through local field potential recordings across specific frequency bands during immobility in awake rats.

Our evaluation confirmed ASD-like phenotypes, including social deficits, repetitive behaviors, cognitive impairments, and emotional dysregulation. Significant differences in membrane properties and firing activities were revealed between the dHPC and vHPC regions, examining network alterations and intrinsic neuronal properties. Notably, autism induction increased excitability in dorsal CA1 neurons compared to ventral neurons in the autism-like group. Analysis of delta, theta, and gamma frequency bands showed distinct spectral power differences between control and autism-like groups exposed to VPA. Autistic-like rats exhibited higher delta and theta power, with a significant impact on gamma activity, specifically in the dHPC.

These findings provide novel insights into the behavioral and electrophysiological alterations in a prenatal VPA-exposed autistic-like model, emphasizing hippocampal hyperexcitability's role in ASD. The results underscore the complexity of anatomical and functional distinctions between the dHPC and vHPC, highlighting spectral dynamics and potential pathological alterations in oscillatory patterns under neuropsychiatric conditions.