Biology subjects

Adlakha, A.

Publications and source records attributed to Adlakha, A..

3 recordsLinked to original sources

bioRxiv2024

Mouse olfactory system acts as anemo-detector and -discriminator

Airflow detection while smelling is a fundamental requirement for olfaction, yet the mechanisms underlying such multimodal processing in the olfactory system remain unknown. We report here that mice can learn to accurately discriminate airflow with parallel processing of both mechanical and chemical stimuli revealed by modulated sniffing and refined calcium signaling in the olfactory bulb inhibitory network. Genetic perturbation of AMPAR function and optogenetic control bidirectionally shifted airflow discrimination learning pace, with contrasting phenotypes observed for odor learning, engagement of inhibitory circuits, and setting the optimal inhibition level for stimulus refinement. Multimodal odor-airflow stimuli at subthreshold levels enhanced learning, demonstrating that mechanical stimuli heighten olfactory perception. Our results, thus explain the multimodality of olfaction, and reveal an unexplored dimensionality of odor perception.

neuroscience↗

bioRxiv2024

A tactile discrimination task to study neuronal dynamics in freely-moving mice

Sensory discrimination tasks are valuable tools to study neuronal mechanisms of perception and learning. Most discrimination tasks for electrophysiological and imaging studies in rodents require the animals to be head-fixed. However, implementing neurophysiological recordings into more ethologically realistic settings with unrestrained animals has been challenging. Here, we introduce a whisker-dependent discrimination task for freely moving mice, integrating electrophysiology and calcium imaging with cellular resolution. In this go/no-go paradigm, male mice learned to discriminate aperture widths within days while foraging on a linear platform. The setups versatility enables exploration into diverse behavioral aspects, including tactile discrimination thresholds, valence-dependent behavior, and cognitive flexibility following repeated task rule reversals. Rule learning was highly stereotypical, fast and reproducible across individual mice. Electrophysiological recordings revealed distributed tactile processing across the thalamocortical system, with subsets of units encoding both movement- and stimulus-related features. Sensory encoding was strongly modulated by behavioral state, with neurons tuned to locomotion, whisking, whisker angle and phase, head angle, and spatial position. By enabling simultaneous extracellular recordings and calcium imaging within the same freely moving paradigm, this approach allows for precise synchronization of neural activity with multiple behavioral readouts. This paradigm provides a versatile tool to elucidate neural mechanisms of cognition and sensory processing in naturalistic conditions.

neuroscience↗

bioRxiv2023

Schwann cells modulate nociception in neurofibromatosis 1

Pain of unknown etiology is frequent in individuals with the tumor predisposition syndrome Neurofibromatosis 1 (NF1), even when tumors are absent. Schwann cells (SC) were recently shown to play roles in nociceptive processing, and we find that chemogenetic activation of SCs is sufficient to induce afferent and behavioral mechanical hypersensitivity in mice. In mouse models, animals show afferent and behavioral hypersensitivity when SC, but not neurons, lack Nf1. Importantly, hypersensitivity corresponds with SC-specific upregulation of mRNA encoding glial cell line derived neurotrophic factor (GDNF), independent of the presence of tumors. Neuropathic pain-like behaviors in the NF1 mice were inhibited by either chemogenetic silencing of SC calcium or by systemic delivery of GDNF targeting antibodies. Together, these findings suggest that Nf1 loss in SCs causes mechanical pain by influencing adjacent neurons and, data may identify cell-specific treatment strategies to ameliorate pain in individuals with NF1. Graphical AbstractGDNF released from Schwann cells acts on sensory neurons leading to mechanical hypersensitivity and pain-like behaviors in preclinical models of NF1. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=181 SRC="FIGDIR/small/533004v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@d17177org.highwire.dtl.DTLVardef@706f56org.highwire.dtl.DTLVardef@19db1ccorg.highwire.dtl.DTLVardef@3e28d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗