The impact of somatostatin peptide transmission on cortical circuit activity during learning

Authors

• N Ross
• M Arenivar
• H Wang
• C Noh
• H Patel
• HA Tejeda

Abstract

The Prefrontal Cortex (PFC) is regulated by glutamatergic long-range pyramidal inputs that are modulated by local GABAergic interneurons to shape activity of pyramidal outputs. Somatostatin (SST) peptide expression is primarily used as a biomarker for a subpopulation of these GABAergic interneurons. Research shows that subtypes of SST interneurons exist with distinct morphology, connectivity patterns, and layering within the cortex, though little is known about the specific circuit mechanisms underlying SST peptide transmission in the PFC. Previous work in our lab has shown that SST peptide knockout in the PFC produces discrimination deficits, an effect that is recapitulated through SST receptor antagonism during tone-shock association acquisition. It is unknown how distinct SST neurons are activated during learning, as well as how SST peptide transmission shapes pyramidal outputs. Therefore, we monitored single-cell SST neuron activity during a fear discrimination learning task using miniscopes and used a multiple linear regression model to find that SST neuron activity is heterogenous, with distinct neurons encoding aversive cues and footshocks. Using High-Plex in-situ hybridization we identified distinct SST sub-populations and characterized the expression patterns of all 5 SST receptor subtypes in the PFC, revealing broad expression of SSTR1, 3, and 4 throughout the PFC. To start exploring how SST transmission impacts pyramidal neuron output, we used our discrimination learning task along with fiber photometry and c-Fos staining to investigate how the SST peptide alters pyramidal output activity. This study could open avenues for targeted interventions in neuropsychiatric conditions characterized by cortical dysfunction and SST neuropeptidergic dysregulation.

Scientific Focus Area: Neuroscience

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