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Simha, R.

Publications and source records attributed to Simha, R..

2 recordsLinked to original sources

Different Emotional States Engage Distinct Descending Pathways from the Prefrontal Cortex

Effective emotional processing, crucial for adaptive behavior, is mediated by the medial prefrontal cortex (mPFC) via connections to the basolateral amygdala (BLA) and nucleus accumbens (NAc), traditionally considered functionally similar in modulating reward and aversion responses. However, the functional specialization of the mPFC[->]BLA and mPFC[->]NAc pathways in representing affective states remains unclear. We found that while overall firing patterns appeared consistent across emotional states, deeper analysis revealed distinct variabilities. Specifically, mPFC[->]BLA neurons, especially "center-ON" neurons, exhibited heightened activity during behaviors classically associated with anxiety-like states, suggesting their involvement in aversive behavioral regulation. Conversely, mPFC[->]NAc neurons were more active during exploratory and approach-related behaviors, implicating them in the processing of positively valenced behavioral states. Notably, mPFC[->]NAc neurons showed significant pattern decorrelation during social interactions, suggesting a pivotal role in processing social preference. Additionally, repeated win/loss outcomes in the tube test produced distinct hierarchy-dependent behavioral changes and elevated corticosterone levels in loser mice, supporting the biological relevance of these behaviorally defined states. Together, these findings reveal pathway-specific representations of affect-related behavioral states in mPFC circuits and provide a framework for understanding how prefrontal outputs organize adaptive behavior across environmental contexts.

neuroscience↗

MeCP2 deletion impaired layer 2/3-dominant dynamic reorganization of cortical circuit during motor skill learning

Rett Syndrome (RTT) is a severe neurodevelopmental disorder caused by loss of function of the X-linked Methyl-CpG-binding protein 2 (MECP2). Several case studies report that gross motor function can be improved in children with RTT through treadmill walking, but whether the MeCP2-deficient motor circuit can support actual motor learning remains unclear. We used two-photon calcium imaging to simultaneously observe layer (L) 2/3 and L5a excitatory neuronal activity in the motor cortex (M1) while mice adapted to changing speeds on a computerized running wheel. Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2-null circuits firing pattern evolved with improved performance over two weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Since motor deficits and anxiety are core symptoms of Rett, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.

neuroscience↗