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Biology subjects

Naik, A. S.

Publications and source records attributed to Naik, A. S..

3 recordsLinked to original sources

Implicit vs. explicit choice promotes the combination vs. selection of sensorimotor memories under contextual uncertainty

Skilled action requires expressing motor memories as appropriate for the current context, but context is often uncertain. Theoretical models make conflicting proposals about memory expression under contextual uncertainty, predicting belief-weighted combination of memories versus the selection of the most probable memory. We tested these predictions by training human participants to reach in two opposing force fields cued by the direction of a random dot motion stimulus whose coherence varied. When participants moved before reporting dot direction, adaptation scaled with coherence: low-reliability cues produced partial expression of both memories. Fitting Bayesian observer models to behavior favored belief-weighted memory combination. In contrast, when participants reported their choice before moving, adaptation was independent of coherence and model fits favored categorical memory selection. Thus, sensorimotor memories are expressed as either a probabilistic combination or categorical selection, depending on whether participants contextual inference remains implicit or is made explicit at the time of memory expression.

animal behavior and cognition↗

An atlas of healthy and injured cell states and niches in the human kidney

Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, and interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) and spatial imaging technologies to a broad spectrum of healthy reference (n = 42) and disease (n = 42) kidneys. This has provided a high resolution cellular atlas of 100 cell types that include rare and novel cell populations. The multi-omic approach provides detailed transcriptomic profiles, epigenomic regulatory factors, and spatial localizations for major cell types spanning the entire kidney. We further identify and define cellular states altered in kidney injury, encompassing cycling, adaptive or maladaptive repair, transitioning and degenerative states affecting several segments. Molecular signatures of these states permitted their localization within injury neighborhoods using spatial transcriptomics, and large-scale 3D imaging analysis of [~]1.2 million neighborhoods provided linkages to active immune responses. These analyses further defined biological pathways relevant to injury niches, including signatures underlying the transition from reference to predicted maladaptive states that were associated with a decline in kidney function during chronic kidney disease. This human kidney cell atlas, including injury cell states and neighborhoods, will be a valuable resource for future studies.

genomics↗

Smad4 signaling establishes the somatosensory map of basal vomeronasal sensory neurons

The accessory olfactory system is a unique model that can give insights on how the neurons can establish and maintain their identity, and connectivity. The vomeronasal organ (VNO) contains two distinct populations of vomeronasal sensory neurons (VSNs) each with specific innervation patterns to the accessory olfactory bulb (AOB). Though morphogenic signals are critical in defining various neuronal populations, the morphogenic signaling profiles that influence each VSN population remains unknown. Here, we found a pronounced BMP signaling gradient within the basal VSNs. By generating Smad4 conditional mutants, we disrupted canonical TGF-{beta}/BMP signaling in maturing basal VSNs and in all mature VSNs. We show that Smad4 loss-of-function in immature basal neurons leads to a progressive loss of basal VSNs, reduced activation of the remnant basal VSNs, and aberrant glomeruli formation in posterior AOB. However, Smad4 ablation in all mature VSNs does not affect neuronal activity nor survival but causes aberrant glomeruli formation only in the posterior AOB. Our study reveals that Smad4 signaling plays a critical role in mediating development, function, and circuit formation of basal VSNs.

developmental biology↗