Involvement of the Primary Auditory Cortex-Basolateral Amygdala Circuit in Altered Conditioned Fear Memory Retrieval Following Electromagnetic Field Exposure in Mice

BACKGROUND: Electromagnetic field (EMF) exposure is increasingly common and has been implicated in a range of effects on human health. Conditioned fear memory plays a critical role in enabling organisms to respond appropriately to previously encountered threats. Despite growing interest in the neurobiological consequences of EMF exposure, its impact on the neural circuits underlying conditioned fear responses has not been clearly defined. METHODS: Using a mouse model exposed to combined microwave and static magnetic fields, we examined the involvement of the primary auditory cortex-basolateral amygdala (Au1-BLA) circuit in EMF-associated alterations in conditioned fear retrieval. A multifaceted experimental approach was employed, including behavioral assays, viral tracing, genetically encoded calcium imaging, chemogenetic modulation, histopathological analysis, and immunofluorescence. RESULTS: Exposure was associated with reduced conditioned fear memory retrieval, pathological changes in Au1 and BLA tissue ultra-structures, and decreased Nissl bodies in Au1 neurons and Au1-BLA neuronal fiber projections. The attenuation of conditioned fear memory retrieval coincided with decreased calcium activity in Au1 and BLA neurons. Consistently, chemogenetic activation of Au1 calcium-dependent protein kinase II (CaMKII)-expressing neurons enhanced calcium activity in BLA neurons during fear retrieval and was accompanied by changes in cholinergic signaling in the BLA. These findings suggest that cholinergic neuronal populations downstream of the Au1-BLA circuit are sensitive to EMF exposure and may participate in EMF-related modulation of fear retrieval. CONCLUSIONS: Our findings support an association between EMF exposure and altered conditioned fear expression involving functional changes within the Au1-BLA circuit, especially for the changes in calcium activity and chemogenetic modulation of Au1 CaMKII-expressing neurons. This study provides direct experimental evidence linking EMF exposure to circuit-level functional interactions underlying fear memory retrieval.