Biology subjects

Pardasani, M.

Publications and source records attributed to Pardasani, M..

6 recordsLinked to original sources

bioRxiv2026

Hypothalamic tauP301L pathology disrupts pair bonding in monogamous prairie voles

Although dementias primarily affect memory, they also disrupt our closest social relationships, resulting in elevated caregiver burden and worse patient outcomes. However, the mechanistic study of how pathology affects social attachments is limited by the use of laboratory rodents that do not form selective, long-term bonds. Here, in monogamous prairie voles, we expressed dementia-causing tauP301L in the paraventricular hypothalamus of 12- and 18-month-old animals, and separately, from birth through 18-months, across hippocampocortical regions. Hippocampocortical expression of tauP301L did not yield deficits in social or non-social dementia-related phenotypes. In contrast, tauP301L expressed in the hypothalamus yielded sex- and age-dependent social bonding deficits. 18-month males with hypothalamic tau pathology failed to form bonds and displayed blunted sociability, effects that converged across bonding assays. In addition, healthy 18-month males paired with a hypothalamic tau-expressing female also showed reduced partner preference, suggesting that pathology exerts vicarious effects on partners. Social behavior of both healthy females and those expressing tauP301L were unaffected. 18-month tauP301L males also showed elevated oxytocin fluorescence. These findings establish direct and vicarious disruptions to pair bonding induced by hypothalamic tau pathology in male prairie voles, potentially via altered oxytocin signaling.

neuroscience↗

bioRxiv2026

A transient hypothalamic CRH signal coordinates social investigation in mice

Successful navigation of the social environment depends on the ability to rapidly evaluate conspecifics and adjust behaviour accordingly. Encounters with unfamiliar individuals are particularly challenging because they introduce uncertainty about how the interactions may unfold. Such social encounters can lead to beneficial or detrimental outcomes, making rapid assessment critical for survival; yet the neural mechanisms underlying this process remain poorly understood. Corticotropin-releasing hormone synthesizing neurons in the paraventricular nucleus of the hypothalamus (CRHPVN), traditionally viewed as the canonical endocrine controllers of the stress response, have been implicated in processing behaviourally relevant environmental and social information, including the investigation of stressed conspecifics. However, their role in rapidly evaluating conspecifics during social encounters remains unclear. Here, using fibre photometry and optogenetics during ethologically relevant social encounters, we show that CRHPVN neurons exhibit a rapid, transient increase in activity that precedes investigative behaviour. This signal scales with social context, is elevated during exposure to unfamiliar relative to familiar conspecifics, persists across novel environments, and generalizes across unfamiliar strains. In contrast, interactions with juvenile conspecifics and inanimate objects do not elicit this differential activity, indicating that CRHPVN recruitment is not driven solely by novelty. Critically, temporally specific inhibition of CRHPVN neurons during this brief activity window produces lasting changes in behaviour beyond the period of inhibition, including the reduction of appropriate social investigation, indicating that this transient activity is necessary for gating subsequent social behaviour. Together, these findings identify CRHPVN neurons as a rapid integrative node linking hypothalamic function to social evaluation.

neuroscience↗

bioRxiv2025

Hypothalamic CRH neurons gate rapid social appraisal of conspecifics

Successful navigation of the social environment requires rapid evaluation of conspecifics to distinguish safe from threatening encounters. While the corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN) are well known for orchestrating endocrine stress responses, their role in real-time social appraisal is unknown. Here, using fibre photometry and optogenetics during ethologically relevant social interactions, we show that CRHPVN neurons exhibit a rapid, transient increase in activity that precedes sniffing, an investigative behaviour through which mice gather social information. This transient signal scales with social context: it is heightened during interactions with unfamiliar and aggressive conspecifics and significantly reduced toward familiar partners. Inhibiting these neurons selectively diminished anogenital sniffing, demonstrating their necessity for optimal social evaluation. Strikingly, across repeated exposures to the same conspecific, behavioural investigation declined while CRHPVN activity remained robust, revealing a dissociation between neuronal and behavioural habituation. This persistence suggests that CRHPVN neurons encode stable neural representation of threat during social encounters. Together, our findings identify CRHPVN neurons as a fast, integrative node linking endocrine stress control to rapid social decision-making.

neuroscience↗

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↗

bioRxiv2022

Uncertainty revealed by delayed responses during olfactory matching

Matching of olfactory stimuli involves both sensory and higher cognitive functioning. Different decision processes such as detection and discrimination, along with holding the perceived information are involved during the matching process. Accuracy and decision times, the interdependent readouts, can define the uncertainty involved in matching of sensory stimuli. To probe sensory and cognitive functions involving olfactory system in human subjects, we have developed a novel olfactory matching paradigm using an automated custom-built olfactory-action meter. With precise and consistent odor delivery and real-time data analysis, our system automates the entire process without any intervention by the experimenter, making it suitable as a diagnostic tool for quantifying olfactory and neurocognitive fitness. In around 400 healthy human subjects, with mean detection accuracy of 90%, we observed significantly better olfactory matching performance for simple monomolecular odors, in comparison to complex binary odor mixtures. Odor matching accuracy declined significantly with the increase in odor complexity. Olfactory matching was more rapid when subjects made correct versus incorrect decisions, indicating perceptual certainty. Subjects also took longer matching time for complex odors compared to simple odor stimuli. Thus, olfactory matching that provides a combined readout of sensory and cognitive fitness, establishes a direct link between the performance accuracy and the certainty of decisions.

neuroscience↗

bioRxiv2019

Multimodal Learning of Pheromone Locations

Memorizing pheromonal locations is critical for many mammalian species as it involves finding mates and avoiding competitors. In rodents, pheromonal information is perceived by the main and accessory olfactory systems. However, the role of somatosensation in context dependent learning and memorizing of pheromone locations remains unexplored. We addressed this problem by training female mice on a multimodal task to locate pheromones by sampling volatiles emanating from male urine through the orifices of varying dimensions or shapes that are sensed by their vibrissae. In this novel pheromone location assay, female mice preference towards male urine scent decayed over time when they were permitted to explore pheromones v/s neutral stimuli, water. On training them for the associations involving olfactory and whisker systems, it was established that they were able to memorize the location of opposite sex pheromones, when tested 15 days later. This memory was not formed either when the somatosensory inputs through whisker pad were blocked or when the pheromonal cues were replaced with that of same sex. The association between olfactory and somatosensory systems were further confirmed by the enhanced expression of the Activity regulated cytoskeleton protein. Further, the activation of main olfactory bulb circuitry by pheromone volatiles did not cause any modulation in learning and memorizing non-pheromonal volatiles. Our study thus provides the evidence for associations formed between different sensory modalities facilitating the long-term memory formation relevant to social and reproductive behaviors.

neuroscience↗