Time-Dependent Actions of Corticosterone on Infralimbic Cortex Pyramidal Neurons of Adult Male Rats

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Abstract
Responses to acute stress function to restore homeostasis. Hence, the study of neurophysiological responses to acute stress helps to understand mechanisms underlying adaptive coping in the face of environmental demands. The infralimbic medial prefrontal cortex (IL-mPFC) modulates the switch between behavioral coping styles, and acute stress enhances glutamatergic neurotransmission on mPFC projection neurons. However, the role of acute stress responses and stress hormones on the physiology of IL-mPFC projection neurons during adulthood remains underexplored. Here, we studied rapid and slow effects of acute corticosterone exposure on synaptic transmission and intrinsic membrane excitability in layer 5 pyramidal neurons of the IL (L5-IL PNs) in adult male rats using ex vivo whole-cell patch-clamp of mPFC slices. We report that corticosterone dynamically modulates the physiology of L5-IL PNs in a time-dependent manner. Specifically, corticosterone elicits a strong rapid shift of the excitatory–inhibitory balance toward enhanced excitation with mineralocorticoid (MR) and glucocorticoid receptors (GR) playing complementarily roles. Also, corticosterone rapidly and transiently decreases the firing rate of L5-IL PNs via GR. Moreover, acute stress or corticosterone slowly enhances glutamatergic neurotransmission via MR and GR without modulating inhibitory neurotransmission or intrinsic excitability of adult L5-IL PNs. Our findings highlight the potential relevance of corticosterone effects on L5-IL PNs to promote a homeostatic response in adult male rats. First, corticosterone rapidly attenuates IL intrinsic excitability during the rapid initial phase of the acute stress response. Later on, corticosterone slowly restores IL output function over time to promote adaptive executive responses when context changes.
Funding Information
  • HHS | NIH | National Institute of Mental Health (R01 MH049698)
  • National Institute of Mental Health and Neurosciences (R01 MH127835)
  • U.S. Department of Veterans Affairs (BX005923)

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