NEURONAL CORRELATES OF SALIENCE PROCESSING

Dysfunctional salience processing has been identified across a range of psychiatric disorders, including schizophrenia, autism spectrum disorder, anxiety disorders, depression, and dementia. Although human fMRI studies have defined large-scale networks and key nodes for salience detection, such as the insular cortex for passive and the cingulate cortex for active oddball detection, the underlying neuronal computations enabling these processes remain poorly understood. To address this gap, we employ a multidimensional passive auditory oddball paradigm in mice, combining simultaneous pupillometry, as an objective readout of arousal, with in vivo calcium imaging of excitatory and inhibitory neuronal subpopulations in the anterior insular cortex (aIC). Additionally, optogenetic manipulations dissect the causal contribution of defined neuronal circuits. Our preliminary findings reveal that optogenetic activation of CamK2+ excitatory neurons in the aIC is sufficient to increase arousal, reflected by robust pupil dilation. Furthermore, auditory oddball stimuli reliably evoke pupil dilation responses in both male and female mice, establishing the paradigm as a sensitive measure of salience-related arousal processes. Notably, we identified a distinct population of neurons within the aIC that is selectively active during oddball presentations, suggesting selective encoding of salience within this region. This integrated approach allows us to link cellular-level neuronal activity and circuit mechanisms with behavioral and physiological signatures of salience detection. By bridging the gap between network-level human imaging findings and cellular mechanisms, these studies aim to advance our mechanistic understanding of salience processing and its disruption across psychiatric conditions.