Abstract
Background
The ability to correctly associate cues and contexts with threat is critical for survival,
while the inability to do so can result in threat-related disorders such as PTSD.
The prefrontal cortex (PFC) and hippocampus are well known to play critical roles
in cued and contextual threat memory processing. However, the circuits that mediate
prefrontal-hippocampal modulation of context discrimination during cued threat processing
are less understood. Here we demonstrate the role of a previously unexplored projection
from the ventromedial region of PFC (vmPFC) to the lateral entorhinal cortex (LEC)
in modulating the gain of behavior in response to contextual information during threat
retrieval and encoding.
Methods
We employ optogenetics followed by in vivo calcium imaging in male C57/B6J mice to
manipulate and monitor vmPFC-LEC activity in response to threat-associated cues in
different contexts. We then investigate the inputs to, and outputs from, vmPFC-LEC
cells using Rabies tracing and channelrhodopsin-assisted electrophysiology.
Results: vmPFC-LEC cells flexibly and bidirectionally shape behavior during threat
expression, shaping sensitivity to contextual information to increase or decrease
the gain of behavioral output in response to a threatening or neutral context, respectively.
Conclusion
Glutamatergic vmPFC-LEC cells are a key player in behavioral gain control in response
to contextual information during threat processing and may provide a future target
for intervention in threat-based disorders.
Keywords
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Article info
Publication history
Accepted:
January 11,
2023
Received in revised form:
January 11,
2023
Received:
August 30,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.
