bioRxiv Science⌕ Search

Biology subjects

Karamihalev, S.

Publications and source records attributed to Karamihalev, S..

4 recordsLinked to original sources

Multilevel sex-specific neurobiological signatures of early life adversity

Stress exposure early in life is an established risk factor for adult psychiatric illness, yet these disorders - including anxiety disorders and depression - show significant sex-dependence in prevalence, symptomatology, and treatment response. The biology underlying these differences remains largely unexplored and may contribute to the clinical heterogeneity in anxiety and depression. Here, we characterize the lasting impact of developmental stress on adulthood neurobiology and behavior in mice by combining analyses of multiple levels of brain function, including whole-brain c-Fos mapping, manganese-enhanced MRI and transcriptomics with advanced behavioral phenotyping. Across levels of investigation, we find distinct and often opposite effects of developmental stress depending on sex. These results together showcase the strong influence of sex on how early life adversity affects the onset of stress-related disorders. This work emphasizes the necessity of considering sex when investigating developmental and neurobiological underpinnings of stress-related disorders and displays a vast range of lasting effects of developmental stress on the brain, which provides a valuable resource for future studies aiming to improve psychiatric treatments.

neuroscience↗

Sexually divergent effects of social dominance on chronic stress outcomes in mice

BackgroundSex and social context are two major factors in the development of depression and other stress-related disorders. However, few studies of the effects of stress on rodent behavior and physiology have investigated social context and fewer still have assessed the possibility of sex-specific effects of social context. MethodsWe assessed social dominance of group-living mice during several days of monitoring using a high-throughput automated behavioral tracking system. We then exposed groups from each sex to a three-week chronic mild stress (CMS) procedure, followed by a behavioral test battery. Finally, we used principle component analysis and post-hoc tests to explore the sources of variance in the behavioral outcome data. ResultsWe found stable hierarchies in both sexes, however social dominance in males exhibited several additional associations with behaviors related to locomotion and exploration that were not seen in females. Crucially, pre-stress social dominance status was associated with opposing outcomes on multiple behavioral readouts between the two sexes following CMS. In particular, subordinate male mice and dominant female mice appeared more responsive to the environmental challenge, as observed in anxiety-like and locomotor behaviors. ConclusionsThis work demonstrates that sex differences interact with preexisting social dominance status to alter the effects of chronic stress. It highlights the importance of understanding the interplay between sex and social context and its contribution to individual differences in stress response.

neuroscience↗

Social context and dominance status contribute to sleep patterns and quality in groups of freely-moving mice

In many socially-living species, sleep patterns are subject to group influences, as individuals adjust to the presence, daily rhythms, and social pressures inherent to cohabitation. Disturbances in social functioning are comorbid with sleep problems in many prevalent psychiatric disorders, most notably, autism-spectrum, mood, and anxiety disorders (e.g., [1-3]). Our understanding of the common causality and the interplay between sleep impairment and psychiatric symptomatology could greatly benefit from experimental paradigms that allow simultaneous assessment of both domains of functioning. In laboratory mice, much is known about the sensitivity of sleep quality to a variety of experimental manipulations. Due to existing methodological restrictions, however, sleep studies are typically conducted in single-housed mice, thereby neglecting the influence of social dynamics and group-derived individual differences (however, see [4,5]). Here, we investigated sleep in a semi-naturalistic environment with freely-moving socially-housed groups of male mice using wireless electroencephalographic (EEG) monitoring devices and automated video tracking. In addition to multiple days of continuous behavioral data, we collected over fifty hours of EEG signal per mouse, recording simultaneously from all individuals in a group. We found evidence of in-group synchrony of sleep state patterns. Moreover, social status was a powerful predictor of sleep quality, such that sleep fragmentation, slow-wave sleep power, and rapid eye movement (REM) episode duration differed as a function of dominance status in the group. Finally, acute stress exposure had differential effects on REM sleep during recovery in dominant versus subordinate individuals. These findings highlight the importance of exploring sleep in a social context and are a step toward more informative research on the interplay between social functioning and sleep.

neuroscience↗

Identity domains in complex behavior: Toward a biology of personality

Personality traits offer considerable insight into the biological basis of individual differences. However, existing approaches toward understanding personality across species rely on subjective criteria and limited sets of behavioral readouts, resulting in noisy and often inconsistent outcomes. Here, we introduce a mathematical framework for studying individual differences along dimensions with maximum consistency and discriminative power. We validate this framework in mice, using data from a system for high-throughput longitudinal monitoring of group-housed mice that yields a variety of readouts from all across an individuals behavioral repertoire. We describe a set of stable traits that capture variability in behavior and gene expression in the brain, allowing for better informed mechanistic investigations into the biology of individual differences.

animal behavior and cognition↗