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Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex

Florencia M Bercum, Maria J Navarro Gomez, View ORCID ProfileMichael P Saddoris
doi: https://doi.org/10.1101/2021.07.28.454150
Florencia M Bercum
University of Colorado Boulder
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Maria J Navarro Gomez
University of Colorado Boulder
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Michael P Saddoris
University of Colorado Boulder
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  • ORCID record for Michael P Saddoris
  • For correspondence: michael.saddoris@colorado.edu
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Abstract

Stress experienced early in development can have profound influences on developmental trajectories and ultimately behaviors in adulthood. Potent stressors during brain maturation can profoundly disrupt prefrontal cortical areas in particular, which can set the stage for prefrontal-dependent alterations in fear regulation and risk of drug abuse in adulthood. Despite these observations, few studies have investigated in vivo signaling in prefrontal signals in animals with a history of early life stress (ELS). Here, rats with ELS experience on PND3-5 were then tested on a conditioned suppression paradigm during adulthood. During conditioned suppression, electrophysiological recordings were made in the ventral medial prefrontal cortex (vmPFC) during presentations of a fear-associated cues that resolved both single-unit activity and local field potentials (LFPs). Relative to unstressed controls, ELS-experienced rats showed greater fear-related suppression of lever pressing. During presentations of the fear-associated cue (CS+), neurons in the vmPFC of ELS animals showed a significant increase in the probability of excitatory encoding relative to controls, and excitatory phasic responses in the ELS animals were reliably of higher magnitude than Controls. In contrast, vmPFC neurons in ELS subjects better discriminated between the shock-associated CS+ and the neutral (“safe”) CS- cue than Controls. LFPs recorded in the same locations revealed that high gamma band (65-95 Hz) oscillations were strongly potentiated in Controls during presentation of the fear-associated CS+ cue, but this potentiation was abolished in ELS subjects. Notably, no other LFP spectra differed between ELS and Controls for either the CS+ or CS-. Collectively, these data suggest that ELS experience alters the neurobehavioral functions of PFC in adulthood that are critical for processing fear regulation. As such, these alterations may also provide insight into to increased susceptibility to other PFC-dependent processes such as risk-based choice, motivation, and regulation of drug use and relapse in ELS populations.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 28, 2021.
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Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex
Florencia M Bercum, Maria J Navarro Gomez, Michael P Saddoris
bioRxiv 2021.07.28.454150; doi: https://doi.org/10.1101/2021.07.28.454150
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Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex
Florencia M Bercum, Maria J Navarro Gomez, Michael P Saddoris
bioRxiv 2021.07.28.454150; doi: https://doi.org/10.1101/2021.07.28.454150

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