Distinct Roles of Somatostatin and Parvalbumin Interneurons in Regulating Predictive Actions and Emotional Responses During Trace Eyeblink Conditioning

Summary Learning involves evaluating multiple dimensions of information and generating appropriate actions, yet how the brain assigns value to this information remains unclear. In this study, we show that two types of interneurons (INs) in the primary somatosensory cortex—somatostatin-expressing (SST-INs) and parvalbumin-expressing (PV-INs) neurons—differentially contribute to information evaluation during trace eyeblink conditioning (TEC). An air puff (unconditioned stimulus, US) delivered after a whisker stimulus (conditioned stimulus, CS) elicited both reflexive eye closure and stress-related locomotion. However, only self-initiated, anticipatory eye closure during the CS window, measured via electromyography (EMG), was directly relevant to learning performance. We found that SST-IN activity changes aligned with the learning induced changes of the anticipatory eye blinks during the CS period, correlated with the EMG changes across learning. In contrast, PV-IN activity was positively correlated with stress-related locomotion following the US and showed no learning related changes, suggesting a role in processing the emotional or aversive component of the task. Furthermore, cholinergic signaling via nicotinic receptors modulated both SST- and PV-IN activities, in a manner consistent with their distinctive roles, linking these interneurons to the regulation of learning-related actions and emotional responses, respectively. These findings demonstrate that distinct interneuron populations evaluate different dimensions of information—SST-INs for predictive, adaptive actions and PV-INs for stress-related emotional responses—to guide learning and behavior. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵3 Lead Contact