Biology subjects

Vaidya, S. P.

Publications and source records attributed to Vaidya, S. P..

3 recordsLinked to original sources

bioRxiv2026

Chronic Intermittent Ethanol Exposure Produces Physiological Tolerance and Distinct Behavioral Alterations Across Abstinence in Female Mice

Chronic ethanol consumption produces long-lasting effects on the brain that contribute to persistent behavioral changes. This has been modeled in animals using the chronic intermittent ethanol (CIE) paradigm, which induces escalation of consumption and alterations in affective and cognitive behavior. While this model has been well characterized in male subjects, the effects of CIE in females and long-term effects that persist beyond the acute withdrawal remain relatively underexplored. Here, female C57BL/6J mice were exposed to four weeks of chronic intermittent ethanol (CIE) vapor to induce dependence. Following CIE, mice were evaluated for physiological tolerance to ethanol and alterations in anxiety-like behaviors and memory processing. Using the ethanol responsivity battery (ERB) assay to assess physiological tolerance, we found blunted responsiveness to the intoxicating effects of ethanol in the CIE-exposed females, indicating heightened ethanol tolerance that persists beyond the acute withdrawal phase. A cohort underwent behavioral testing following CIE to characterize changes in anxiety-like behavior, exploration, and memory across abstinence. In early abstinence (<5 days post-CIE), CIE-exposed females showed increased exploratory behavior compared with Air controls. After one week of abstinence, CIE-exposed females displayed impaired object recognition memory. CIE-exposed females also showed increased anxiety-like behavior at protracted abstinence time points, exhibiting hyponeophagia in the novelty-suppressed feeding test at 2 weeks post-CIE. In addition, following cued fear conditioning, we found reduced extinction recall at 4 weeks post-CIE. Together, this work indicates that chronic alcohol exposure leads to increased alcohol tolerance and distinct, persistent alterations in memory and anxiety-like behavior in female mice.

neuroscience↗

bioRxiv2026

Unconstrained Plasticity Disrupts Memory Consolidation in a Mouse Model of Rett Syndrome

Memory impairment is a hallmark cognitive deficit in Rett syndrome (RTT). Yet, long-term memory deficits in RTT animal models remain poorly understood, largely due to the technical challenges inherent in tracking neural activity over extended periods. Here, we used longitudinal two-photon calcium imaging to follow the same population of hippocampal CA1 neurons as female RTT mice and their littermate controls formed cognitive maps of their environment during a spatial learning task. Neural representations in RTT mice were marked by excessive place cell (PC) activity, with individual PCs exhibiting pronounced instability across days. This disrupted single-cell stability propagated to the population level, resulting in unstable ensemble codes that poorly retained previously learned task information. Both excessive PC recruitment and instability could be attributed to a higher incidence of behavioral timescale synaptic plasticity (BTSP) in RTT mice. In wild-type littermates, place-cell consolidation across days is reflected by an increased likelihood of neuron-specific synaptic plasticity at the location of prior PC coding. This cellular mechanism of memory consolidation based on the location of BTSP was disrupted in RTT mice, where excessive and ectopic plasticity reduced PC stability, and degraded long-term stable representations. Backed by theoretical modeling, these results identify a plausible cellular and circuit-level mechanism underlying memory impairments in RTT mice and suggest principles that may be generalized to other neurological disorders involving memory deficits.

neuroscience↗

bioRxiv2023

The formation of an expanding memory representation in the hippocampus

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood1,2. To examine this, we tracked the same population of hippocampal CA1 place cells (PC) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field (PF) and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session, and showed a strong correlation with behavioral performance. Both the initial formation of PCs and their retrieval on subsequent days was accompanied by prominent signs of behavioral timescale synaptic plasticity (BTSP), suggesting that even stable PCs were re-formed by synaptic plasticity each session. Further experimental evidence supported by a cascade-type state model indicates that CA1 PCs increase their stability each day they are active eventually forming a highly stable population. The results suggest that CA1 memory is implemented by an increase in the likelihood of new neuron-specific synaptic plasticity, as opposed to extensive long-term synaptic weight stabilization.

neuroscience↗