Bisphenol A Impairs Spatial Memory by Inhibiting Hippocampal Excitatory Neuronal Response During Learning Events

Bisphenol A (BPA) exposure can impair learning and memory in rodents, but the underlying systematic neural mechanism remains unclear. Due to the important role of the hippocampus for learning and memory, in this study, we systematically investigated the neural circuit, neuron structure, and function of the hippocampus after BPA exposure. First, by employing a virus tracing technique, we observed a decrease in the neural projection ratio of excitatory neural neurons from the “Entorhinal Cortex-Dentate Gyrus-CA3-CA1” and “Entorhinal Cortex-CA1” circuits. Furthermore, BPA exposure led to impairments of the branching complexity and electrophysiological properties of hippocampal neurons. Additionally, fiber photometry experiments revealed that BPA exposure reduces the level of real-time activity in hippocampal excitatory neurons (CA1, CA3, and DG) during the MWM task. To verify the role of hippocampal excitatory neurons in learning and memory impairment caused by BPA, the dorsal hippocampus CA1 neurons were chemogenetically activated, and the spatial memory deficits were rescued. Collectively, our results suggest that BPA exposure impairs the hippocampal neural circuits and neuronal real-time response, leading to the dysfunction of spatial memory in mice. This study expands our understanding of the neurotoxic mechanisms of BPA at the mesoscopic neural level and provides a potential strategy for rescuing BPA-induced learning and memory impairments.