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 demand. 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 (HPC‐mPFC) 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 HPC‐mPFC theta dynamics were observed. These findings support the hypothesis that HPC‐mPFC theta signaling is sensitive to both biological sex and female estrous stage. These findings establish novel research avenues concerning sex as a biological variable and effects of gonadal hormone status on HPC‐mPFC network activity as it pertains to threat evaluation biomarkers.

Highlights

  • The brain’s ability to adaptively respond to the body’s surroundings relies on synchronous oscillatory activity in the local field potentials (LFPs) of interconnected brain regions [1]

  • Adult male and female rats were placed into a familiar arena, and LFPs from PrL, infralimbic cortex (IL), ventral hippocampus CA1 (vHPC), and dorsal hippocampus CA1 (dHPC) were simultaneously recorded over many trials

  • Neither biological sex nor female estrous stage significantly affected the power across a range of known brain rhythms

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Summary

INTRODUCTION

The brain’s ability to adaptively respond to the body’s surroundings relies on synchronous oscillatory activity in the local field potentials (LFPs) of interconnected brain regions [1]. Several findings in male mice have demonstrated that theta frequency (~8 Hz) phase synchrony in vHPC-mPFC LFPs underlies innate avoidance behavior in approach-avoidance conflict tasks such as the elevated plus maze [13,14,15] These findings have direct relevance to understanding the neurobiology of innate threat processing, and are of value in modeling “anxiety-like” states in rodents, as homologous brain regions to the rodent HPC and mPFC are involved in human expression of anxiety states and recall of extinguished fear [16,17,18,19]. Theta band power correlations between vHPC-PrL were significantly greater in males than females, but female estrous stage had no significant impact (Fig. 3c). Theta band power correlations between dHPC-PrL were not significantly affected by biological sex or female estrous stage (Fig. 3d). Females’ dHPC-IL theta phase lags were more reliably distributed than males’

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