Sex differences and effects of estrous stage on hippocampal-prefrontal theta communications

Abstract

Effective communication between the mammalian hippocampus and neocortex is essential to certain cognitive-behavioral tasks critical to survival in a changing environment. Notably, functional synchrony between local field potentials (LFPs) of the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC) within the theta band (4-12 Hz) underlies innate avoidance behavior during approach-avoidance conflict tasks in male rodents. However, the physiology of vHPC-mPFC communications in females remains unestablished. Furthermore, little is known about how mPFC subdivisions functionally interact in the theta band with hippocampal subdivisions in both sexes in the absence of task demands. Given the established roles of biological sex and gonadal hormone status on innate avoidance behaviors and neuronal excitability, here, we characterize the effects of biological sex and female estrous stage on hippocampal-prefrontal theta signaling in freely-moving female and male rats. LFPs from vHPC, dorsal hippocampus (dHPC), mPFC-prelimbic (PrL), and mPFC-infralimbic (IL) were simultaneously recorded during spontaneous exploration of a familiar arena. Data suggest that theta phase and power in vHPC preferentially synchronize with PrL; conversely, dHPC and IL preferentially synchronize. Males displayed greater vHPC-PrL theta synchrony than females, despite similar regional frequency band power and inter-regional coherence. Additionally, several significant estrous-linked changes in hippocampal-prefrontal theta dynamics were observed. These findings support the hypothesis that biological sex and female estrous stage can both affect hippocampal-prefrontal theta signaling in a familiar environment. These findings establish novel research avenues concerning sexual dimorphisms and effects of gonadal hormone status in HPC-mPFC network activity pertaining to threat evaluation biomarkers. SIGNIFICANCE STATEMENTEffective signaling between subregions of the hippocampus and the prefrontal cortex underlies several cognitive-behavioral processes necessary for survival. Theta-frequency synchrony between the local fields of the ventral hippocampus and the prefrontal cortex regulates innate avoidance behavior in male rodents. However, this circuit remains understudied in females, despite its potential utility in research modeling the neurobiology of anxiety disorders (and sex differences therein). Here, we demonstrate that both biological sex and female hormone status have multifaceted effects on hippocampal-prefrontal theta-frequency signaling in freely-moving rats during exploration of a familiar arena. These findings provide insight into how biological sex and female estrous stage shape the way in which these circuits may represent the potential for threat.