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Chitale, S.

Publications and source records attributed to Chitale, S..

2 recordsLinked to original sources

Flexible behavioral adjustment to frustrative nonreward in anticipatory behavior, but not in consummatory behavior, requires the dorsal hippocampus

The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HCs function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in an 8-maze task after reducing the quantity of sugar pellet rewards. In Experiment 2, whereas chemogenetic inhibition of the dorsal HC left consummatory responses unaffected after a sucrose downshift, it significantly disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3-5 used peripheral lipopolysaccharide (LPS) treatment and found an increase in cytokine levels in the dorsal HC (dHC, Experiment 3), impaired anticipatory choice (Experiment 4), but no effect on consummatory behavior in two reward-downshift tasks. In Experiment 6, after a sucrose downshift, we found no evidence of increased activation in either the dorsal or ventral HC, as measured by c-Fos expression. These findings highlight the HCs pivotal role in adaptively modulating anticipatory behavior in response to frustrative nonreward, while having no effect on adjustments of consummatory behavior. Spatial orientation, memory update, choice of reward signals of different value, and anticipatory vs. consummatory adjustments to reward downshift are discussed as potential mechanisms that could elucidate the specific effects observed from HC manipulations.

neuroscience↗

A semiconductor 96-microplate platform for real-time impedance-based high-throughput screening

Profiling compounds and genetic perturbations via high-content imaging has become increasingly popular for drug discovery, but the technique is limited to endpoint images of fixed cells. In contrast, electronic-based devices offer label-free, functional information of live cells, yet current approaches suffer from low-spatial resolution or single-well throughput. Here, we report a semiconductor 96-microplate platform designed for high-resolution real-time impedance "imaging" at scale. Each well features 4,096 electrodes at 25 {micro}m spatial resolution while a miniaturized data interface allows 8x parallel plate operation (768 total wells) within each incubator for enhanced throughputs. New electric field-based, multi-frequency measurement techniques capture >20 parameter images including tissue barrier, cell-surface attachment, cell flatness, and motility every 15 min throughout experiments. Using these real-time readouts, we characterized 16 cell types, ranging from primary epithelial to suspension, and quantified heterogeneity in mixed epithelial and mesenchymal co-cultures. A proof-of-concept screen of 904 diverse compounds using 13 semiconductor microplates demonstrates the platforms capability for mechanism of action (MOA) profiling with 25 distinct responses identified. The scalability of the semiconductor platform combined with the translatability of the high dimensional live-cell functional parameters expands high-throughput MOA profiling and phenotypic drug discovery applications.

bioengineering↗