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Adwanikar, H.

Publications and source records attributed to Adwanikar, H..

3 recordsLinked to original sources

Modulation of exploration-avoidance behaviors by vmPFC-projecting BLA neurons

The ventromedial prefrontal cortex (vmPFC) is known to regulate exploration-avoidance behaviors. Separately, the basolateral amygdala (BLA), which plays a pivotal role in interpreting the emotional valence of external stimuli, is known to send information about aversive cues to the mPFC. Here, we investigated the role of vmPFC-projecting BLA neurons in modulating exploration-avoidance behaviors. We selectively and reversibly inhibited this subset of BLA neurons using a projection-defined chemogenetic approach in mice engaged in a classic unconditioned exploration-avoidance task, the elevated zero maze (EZM). Saline injection served as a control for administration of the chemogenetic ligand CNO. We found that inhibiting vmPFC-projecting BLA neurons with CNO injections promotes avoidance behaviors. This effect could not be attributed to the effects of injection. It could also not be attributed to repeated maze exposure because, whereas we observed behavioral habituation in naive mice following repeated exposure at 1 hr, in mice mimicking treatment manipulation (IP injection), no habituation was observed at this timepoint. Together, our results reveal that vmPFC-projecting BLA neurons promote safety rather than aversive signals in the context of unconditioned exploration-avoidance behavior. Surprisingly, these findings are directly opposed to previous work that suppressed BLA projection fibers in the mPFC. These contrasting results suggest pathway-dependent roles of mPFC-projecting BLA neurons (direct axonal vs. complex somatic, due to direct + indirect), or alternatively, specializations in the roles of mPFC subregions (vmPFC vs. dmPFC) in exploration-avoidance behavior. Our results also provide guidance for future experimental designs involving repeated exposure to the EZM.

neuroscience↗

Robust characterization of selectivity of individual neurons to distinct task-relevant behavioral states using calcium imaging

Investigations into the neural basis of behavior have recently employed fluorescence imaging of calcium dynamics in a variety of brain areas to measure neural responses. However, across studies, diverse and seemingly subjective methodological choices have been made in assessing the selectivity of individual neurons to task-relevant behavioral states. Here, we examine systematically the effect of different choices in the values of key parameters from data acquisition through statistical testing on the inference of the selectivity of individual neurons for task states. We do so by using as an experimental testbed, neuronal calcium dynamics imaged in the medial prefrontal cortex of freely behaving mice engaged in a classic exploration-avoidance task involving spontaneous (animal-controlled) state transitions - navigation in the elevated zero maze (EZM). We report that a number of key variables in this pipeline substantially impact the selectivity label assigned to neurons, and do so in distinct ways. By quantitatively comparing newly defined accuracy and robustness metrics for all the 128 possible combinations of levels of the key parameters, we discover in a data-driven manner, two optimal combinations that reliably characterize neuronal selectivity - one using discrete calcium events and another using continuous calcium traces. This work establishes objective and standardized parameter settings for reliable, calcium imaging-based investigations into the neural encoding of task-states.

neuroscience↗

Neural markers of vulnerability to anxiety outcomes following traumatic brain injury

Anxiety outcomes following traumatic brain injury (TBI) are complex, and the underlying neural mechanisms are poorly understood. Here, we developed a multidimensional behavioral profiling approach to investigate anxiety-like outcomes in mice that takes into account individual variability. Departing from the tradition of comparing outcomes in TBI versus sham groups, we identified animals within the TBI group that are vulnerable to anxiety dysfunction by applying dimensionality reduction, clustering and post-hoc validation to behavioral data obtained from multiple assays for anxiety at several post-injury timepoints. These vulnerable animals expressed distinct molecular profiles in the corticolimbic network, with downregulation in GABA and glutamate, and upregulation in NPY markers. Indeed, among vulnerable animals, not resilient or sham controls, severity of anxiety outcomes correlated strongly with expression of molecular markers. Our results establish a foundational approach, with predictive power, for reliably identifying maladaptive anxiety outcomes following TBI and uncovering neural signatures of vulnerability to anxiety.

neuroscience↗