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Updated: Apr 4, 2026

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Trace Fear Conditioning in Mice
Published on: March 20, 2014
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Cue-Dependent Fear Learning Drives Nucleus Accumbens Spine Plasticity.
Desh Deepak Ratna1, Cortez Gray2, Eugene Lee1
1Department of Psychiatry, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.
Biorxiv : the Preprint Server for Biology
|April 3, 2026
Summary
Synaptic plasticity in nucleus accumbens neurons is driven by cue-dependent learning, not stress alone. This suggests these neurons encode threat cues, potentially increasing future stress responses.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
Background:
- Nucleus accumbens (NAc) dopamine 2 receptor expressing medium spiny neurons (D2-MSNs) play a role in stress and aversive learning.
- Repeated stress is known to increase excitatory spine density in these neurons, but whether this is due to cue-specific learning or generalized stress is unclear.
Purpose of the Study:
- To investigate whether synaptic plasticity in NAc D2-MSNs is a result of cue-specific learning or generalized stress.
- To dissociate associative plasticity from the effects of foot shock stress.
Main Methods:
- Utilized Pavlovian fear conditioning in Tac1-Cre/Tdtomato mice.
- Dissociated associative plasticity from foot shock stress effects.
- Examined physiological outcomes of acute fear conditioning with and without a cue.
Main Results:
- Acute fear conditioning yielded different outcomes depending on the presence or absence of a cue.
- Seven days of conditioning consolidated cue learning, increasing excitatory transmission frequency and total spine density.
- Repeated foot shock exposure alone did not induce synaptic remodeling.
Conclusions:
- Morphological changes supporting synaptic plasticity on NAc D2-MSNs are driven by cue-dependent learning, not solely by foot shock stress.
- NAc D2-MSNs are proposed to encode learning and responses to threat cues.
- This encoding may contribute to heightened stress responsivity in the future.
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