Somatostatin neurons and learning

___________ Somatostatin-expressing (SST) GABAergic neurons are a key component of neocortical circuits, implicated in sensory perception, plasticity, and disease. Understanding SST function has been hampered by the diverse transcriptional and electrophysiological profiles of this inhibitory neuronal class, with between 10 and nearly 40 different proposed subtypes. We have identified a molecularly-defined subset of SST neurons localized to superficial layers of mouse sensory cortex that show response plasticity when sensory stimuli predict reward outcome, but not when stimuli and rewards are uncoupled. This critical insight provides a foothold to bridge the local network properties of specific subtypes of SST neurons with brain-scale signals involved in reinforcement learning. Here we will define the circuit properties of this SST subtype and how they change during whisker- dependent sensory association learning, taking advantage of cell-type and pathway-specific analysis in acute brain slices. In parallel, we will use longitudinal Ca++ to image these SST neurons during learning, adapting our freely-moving task to a head-fixed training paradigm. In vivo imaging will also enable us to dynamically manipulate stimulus-reward contingencies during learning, to determine how predictive sensory input, expectation, and surprise regulate SST response properties. Finally, based on our preliminary data that implicates neuromodulator activity in SST response plasticity during stimulus-reward pairing, we will test the role of cortical norepinephrine and serotonin in regulating SST activity during learning. Project Number: 1R01NS147337-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: ALISON BARTH | Institution: CARNEGIE-MELLON UNIVERSITY, PITTSBURGH, PA | Award Amount: $455,645 | Activity Code: R01 | Study Section: Learning, Memory and Decision Neuroscience Study Section[LMDN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11279230