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Krishnamurthy, E.

Publications and source records attributed to Krishnamurthy, E..

2 recordsLinked to original sources

An adaptive noradrenergic-prefrontal circuit for innate avoidance of heights

Innate preferences determine how animals interact with the environment, but how experience refines the neural processes underlying those intrinsic motivations is not well understood. Here we develop a virtual pole descent task which permitted in which mice can repeat many trials without habituation of height-dependent avoidance. Mice adjusted their choices based on recent trial outcomes without externally imposed behavioral reinforcement or punishment. Using this paradigm, we found that noradrenergic signaling enhances height avoidance while experience refines the prefrontal cortex population representation of the task. Inhibiting locus coeruleus norepinephrine neurons reduced safe choices in apparently tall visual height stimuli, while stimulating their projections to prelimbic cortex enhanced safe decision-making. Anticipatory norepinephrine in prelimbic cortex correlated with height avoidance across animals and reflected trial outcome history. Miniscope calcium imaging revealed prelimbic neurons tracked progress in the task. At the population level, experience induced improvements in the decoding of position which correlated strongly with behavioral improvements. With experience, neural trajectories became less variable during the task and reliability of representations correlated with behavioral improvement. Together these results reveal that innate threat experience can induce prefrontal cortical refinement without externally imposed reinforcement. Innate behavioral preference is thus maintained while the neural processes underlying it evolve, suggesting flexibility in neural circuits for interacting with hardwired environmental motivations.

neuroscience↗

MDMA enhances prefrontal plasticity and representational drift during fear extinction

Fear extinction requires dynamic updating of cortical representations, yet the neural mechanisms underlying successful extinction remain poorly understood. Some psychoactive substances induce structural plasticity in medial prefrontal cortex (mPFC), possibly underlying their therapeutic potential. Here we investigated whether MDMA, which enhances fear extinction, induces prefrontal structural and functional plasticity, and measured its effects on ensemble representations during extinction. Longitudinal two-photon microscopy revealed that MDMA increased spine density and spinogenesis across prefrontal subregions. Miniscope Ca{superscript 2} imaging in infralimbic cortex (IL) during fear extinction revealed that IL became more correlated with the suppression of freezing behavior, consistent with a strengthening of its role in extinction. Longitudinal cell registration demonstrated accelerated representational drift across days in MDMA-treated mice; this effect was strongest in a functionally defined subpopulation of neurons that showed suppression of activity to conditioned cues. These findings demonstrate that MDMA facilitates structural and functional neuroplasticity, potentially underlying its enhancement of extinction learning.

neuroscience↗