Blunted synaptic plasticity in the vHPC-mPFC pathway involving the working memory deficits of mice with perinatal bisphenol-A exposure

Working memory guides human decisions and actions by temporarily holding and manipulating information, yet it has been well-documented as impaired in children with bisphenol A (BPA) exposure. However, neither its underlying neural circuit mechanism nor synaptic basis has been rigorously examined. In the present study, mouse pups were exposed to BPA from dams with BPA exposure (0.735 mg/kg/day) during the gestation and lactation periods to simulate children exposure situation. We found that there was a significant decline in working memory during T maze and objective recognition testing. The in vivo electrophysiological results showed that there was a noticeable decline in theta (θ)/gamma (γ) oscillation power in the medial prefrontal cortex (mPFC) and θ-γ oscillation coupling in the ventral hippocampus (vHPC)-mPFC circuit during retrieval of spatial cues (choice phase) in the novelty-driven T maze task. This fail retrieval of spatial cues and network activity appears to be mediated by down-regulated synaptic plasticity within the vHPC-mPFC circuit. Further patch-clamp recording results revealed a pronounced decrease in the amplitude, rather than the frequency, of excitatory postsynaptic currents (EPSCs) in the mPFC of BPA-exposed mice. Importantly, the spine density of pyramidal neurons and the expression of excitatory receptors (GluA1) in the mPFC were significantly decreased after BPA exposure, providing the postsynaptic basis for BPA-induced synaptic plasticity impairment. Our findings in this study provide rigorous physiological and structural mechanism at circuit and synaptic level underlying working memory deficits resulting from BPA exposure during the critical developmental stage.