Nucleus accumbens (NAc) dopamine 2 receptor-expressing medium spiny neurons (D2-MSNs) are involved in stress and aversive fear learning and stress responses, where repeated exposure to aversive stimuli and stress increases excitatory spine density. Whether this plasticity reflects cue-specific aversive fear learning or a cue-independent response remains unknown. Using Pavlovian fear conditioning, we dissociated associative plasticity from that induced by foot shock exposure in the NAc.
Acute fear conditioning produced distinct physiological outcomes between aversive stimuli in the presence or absence of a cue. Conditioning for 7 days consolidated cue learning and increased excitatory transmission frequency via an increase in the total spine density. However, repeated exposure to foot shock did not lead to this synaptic remodeling.
Our results suggest that morphological changes supporting synaptic plasticity in NAc D2-MSNs are due to cue-dependent aversive fear learning, but not foot shock stress alone. We propose that NAc D2-MSNs encode fear learning and responses to threat cues, which may heighten stress responsivity. This work was supported by NIH/NIMH R00MH123673, the Department of Drug Discovery and Biomedical Sciences in the College of Pharmacy at the University of South Carolina, Brain and Research Behavior Foundation Young Investigator’s Grant, and the Department of Psychiatry and the Medicine Institute for Neuroscience Discovery (UM-MIND) at the University of Maryland School of Medicine.
Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, 21201, USA Desh Deepak Ratna, Eugene Lee & T. Chase Francis Program in Neuroscience, University of Maryland Baltimore, Baltimore, MD, 21201, USA Medicine Institute for Neuroscience Discovery (UM- MIND), University of Maryland School of Medicine, Baltimore, MD, 21201, USA Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, 29208, USA Cortez Gray, Charalampos Kiaris & Makenna Hamilton The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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