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

Numerous studies have demonstrated that exposure to electromagnetic fields (EMFs) can impair cognitive function and emotional behavior. In this context, conditioned fear memory is particularly relevant because the dysregulation of this memory is a defining characteristic of post-traumatic stress disorder (PTSD). However, the impact of EMFs on the underlying neural circuits remains largely unexplored. Two key circuits involved in processing and retrieving fear memories are the primary auditory cortex (Au1) and the basolateral amygdala (BLA). This study investigates how exposure to a static magnetic field combined with radiofrequency radiation affects the Au1-BLA circuit at behavioral, structural, and signal transmission levels.

Ten-week-old C57BL/6N mice were randomly divided into four groups: Group 1: sham-exposed control; Group 2: magnetic field exposure (MF; 100 mT for 1 h/day); Group 3: RF exposure (RF; 9.375 GHz unmodulated carrier frequency, SAR 2.58 W/kg for 15 min/day); and Group 4: combined exposure (MF and RF). Thermal effects were ruled out by rectal temperature measurements. The animals underwent auditory fear conditioning. Activation of fear memory was assessed by freezing behavior. In addition, auditory function and structural-morphological tissue changes in the Au1 and BLA regions were analyzed. Furthermore, projection neurons (Au1-BLA connection) and the calcium dynamics of Au1 and BLA neurons were investigated. To characterize their function, (CaMKII-expressing) excitatory Au1 neurons and examined their downstream excitatory and inhibitory neurons in the BLA were activated or inhibited. Depending on the analysis, six or eight samples per group (n = 6|8) were used.

Only the group exposed to a combination of MF and RF fields showed significant changes in freezing behavior after seven days, a clear sign of an impairment in fear memory. Hearing function remained unchanged. Compared to the control group, structural changes were observed in the exposed groups, including mitochondrial swelling, chromatin condensation, and endoplasmic reticulum degranulation. These changes were more pronounced in groups exposed to a combination of fields than in groups exposed to MF or RF fields alone, and in Au1 neurons than in BLA neurons. Consistent with this finding, Nissl bodies were significantly reduced in Au1 neurons exposed to a combination of fields. The connection between the Au1 and BLA areas (neuron projection) exhibited weakened signal transmission. Correspondingly, calcium activity during the fear response was significantly reduced in the combined-field group. Functionally, chemically activating excitatory Au1 neurons partially restored fear behavior and BLA calcium dynamics, while the chemical inactivation of these neurons exacerbated the phenotype. In the BLA area, combined exposure resulted in increased activation of excitatory neurons but not inhibitory neurons. This effect was attenuated by Au1 activation.

The results demonstrate that exposure to a static magnetic field and RF-EMF weakens the Au1-BLA circuit functionally, impairing fear memory retrieval. Functional analysis suggests that reduced glutamatergic output from Au1, coupled with dysregulation of downstream cholinergic BLA neurons, plays a role in this impairment. The observed impairment is not due to disturbances in peripheral auditory function or initial sensory stimulus processing.

Editor’s note:

The present study is distinguished by its multimodal approach. Behavioral testing, chemogenetics, calcium imaging, electron microscopy, and viral tracing of projection neurons were combined to establish a consistent chain of evidence. This study has potential clinical relevance due to its connection to post-traumatic stress disorder (PTSD). However, data from animal studies cannot be directly transferred to humans. The static magnetic field strength is below the ICNIRP safety threshold of 400 mT, and the RF-EMF's specific absorption rate (SAR) of 2.58 W/kg is in the ballpark of the permissible exposure limit for the head, which is 2 W/kg. EMF effects primarily occur synergistically, as in real-world wireless communication technologies. However, the extremely low frequency (ELF) component of wireless communication technologies differs significantly from the static magnetic field used here because it is pulsed and considerably weaker. (RH)