Abstract
Somatostatin Interneurons in Emotion Regulation
Biological psychiatry (1969), Vol.93(9 Suppl), pp.S4-S4
05/01/2023
DOI: 10.1016/j.biopsych.2023.02.031
Abstract
Background
Somatostatin-interneurons (SST-INs) maintain inhibitory-excitatory balance in microcircuits throughout the brain. SST-IN activity in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) has been studied during fear learning. However, we investigated the role of BLA SST-INs in learning non-aversive cues and fear suppression, which is not well understood, but is critical to combat generalized fear in psychiatric disorders.
Methods
We used immunohistochemistry and in-vivo imaging to investigate BLA SST-IN activity during fear suppression. We used awake in-vivo multi-site physiology and optogenetics to study how SST-INs contribute to BLA oscillations, mPFC-BLA communication, and behavior.
Results
Animals were differentially fear conditioned that one cue (CS+) is associated with a shock, and one is not (CS-), or underwent fear conditioning and extinction. During retrieval, cFos in BLA SST-INs was selectively upregulated for CS- retrieval during discrimination (n=18 mice, p=0.013), and retrieval of an extinguished CS+ (n=13, p<0.01). Calcium imaging showed that cues evoked a weak SST-IN response during habituation, whereas after discrimination learning, the CS- selectively drove SST-INs (n=306 cells, p=5.3x10-17), a response that depended on the prelimbic (PL) mPFC. Optogenetic inhibition of SST-INs reduced extinction learning and retrieval (n=15, p<0.001), increased CS- evoked theta (6-10 Hz) reset in the BLA (n=6, p=0.009), resulting in more synchronized amygdala population activity, and fear generalization. Optogenetic activation of PL terminals in the BLA improved fear suppression during the CS- (n=8, p=0.012).
Conclusions
During fear suppression, the PL drives BLA SST-INs to filter out sensory input to the BLA, desynchronizing BLA population activity, and preventing a defensive fear response.
Details
- Title: Subtitle
- Somatostatin Interneurons in Emotion Regulation
- Creators
- Ekaterina Likhtik - The Graduate Center, CUNYJoseph Stujenske - Cornell UniversityPia-Kelsey O'Neill - Columbia UniversityCarolina Fernandes-Henriques - The Graduate Center, CUNYItzick Nahmoud - Wayne State UniversitySamantha Goldburg - Northwell HealthAshna Singh - Cornell UniversityLaritza Diaz - Charles E. Schmidt College of MedicineMargarita Labkovich - Icahn School of Medicine at Mount SinaiWilliam Hardin - AmazonScott Bolkan - Neuroscience InstituteThomas Reardon - META HealthTimothy Spellman - University of ConnecticutDaniel Saltzman - Columbia UniversityConor Liston - Cornell UniversityJoshua Gordon - National Institute of Mental Health
- Resource Type
- Abstract
- Publication Details
- Biological psychiatry (1969), Vol.93(9 Suppl), pp.S4-S4
- DOI
- 10.1016/j.biopsych.2023.02.031
- ISSN
- 0006-3223
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 05/01/2023
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984944731602771
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