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Kajs, B. L.

Publications and source records attributed to Kajs, B. L..

2 recordsLinked to original sources

Divergent encoding of active avoidance behavior in corticostriatal and corticolimbic projections

Active avoidance behavior, in which an animal performs an action to avoid a stressor, is crucial for survival and may provide insight into avoidance behaviors seen in anxiety disorders. Active avoidance requires the dorsomedial prefrontal cortex (dmPFC), which is thought to regulate avoidance via downstream projections to the striatum and amygdala. However, the endogenous activity of projection-defined dmPFC subpopulations during active avoidance learning remains unexplored. Here we utilized fiber photometry to record from the dmPFC and its downstream projections to the dorsomedial striatum (DMS) and the basolateral amygdala (BLA) during active avoidance learning in mice. We examined neural activity during conditioned stimulus (CS) presentations, active avoidance, and cued freezing. Both prefrontal projections showed learning-related increases in activity during CS onset throughout active avoidance training. The dmPFC as a whole showed increased activity during avoidance and decreased activity during cued freezing. Finally, dmPFC-DMS and dmPFC-BLA projections showed divergent encoding of active avoidance behavior, with the dmPFC-DMS projection showing increased activity and the dmPFC-BLA showing decreased activity during active avoidance. Our results identify differential prefrontal encoding of active and passive coping behaviors in the same behavioral paradigm and demonstrate divergent encoding of active avoidance in projection-specific dmPFC subpopulations.

neuroscience

Parallel valence processing alterations associated with compulsive behavior in SAPAP3 knockout mice and human OCD

Abnormalities in valence processing - the processing of aversive or appetitive stimuli - may be an underrecognized component of obsessive-compulsive disorder (OCD). Independent experimental paradigms have suggested disturbance of emotional valence systems in OCD, yet no standardized assay has been employed to assess both negative and positive valence processing in clinical studies of OCD patients, either at baseline or in response to therapeutic interventions. Additionally, preclinical rodent models are critical for treatment discovery in OCD, yet investigations examining whether rodent models of compulsive behavior similarly show alterations in valence systems have been limited. We sought to establish paradigms for assessing valence processing across both human OCD patients and in a preclinical rodent model: in OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence); in the SAPAP3 knockout (KO) mouse model of compulsive behavior, we used auditory fear conditioning and extinction (negative valence) and reward-based operant conditioning (positive valence). We find that OCD patients show enhanced negative and impaired positive valence processing, and that performance on valence processing tasks correlates with clinical measures of OCD severity. We further find that SAPAP3 KO mice show heightened negative and impaired positive valence processing alterations similar to those of OCD patients. Our results show parallel valence processing abnormalities in OCD patients and a preclinical rodent model of compulsive behavior, and suggest valence processing alterations as novel therapeutic targets across a translational research spectrum.

neuroscience