Biology subjects

Grammer, J.

Publications and source records attributed to Grammer, J..

3 recordsLinked to original sources

bioRxiv2026

Extended amygdala orchestrates social motivation in socially isolated mice

Juveniles deprived of social contact for an extended period of time demonstrate a broad range of adverse effects on behavior, including increased social aversion. Employing our recently developed integrative assay to assess social aversion, we discovered that social isolation is sufficient to induce decreases in social motivation and increases in social fear and hesitancy. Unsupervised behavioral analyses revealed that social aversion in isolated mice is largely driven by an inflexible, anxiety-like state marked by heightened social vigilance. Using intersectional, projection-specific neural circuit perturbations and in vivo imaging, we discovered that isolation-induced decreases in social motivation are governed by an underexplored projection from the anterodorsal bed nucleus of the stria terminalis (adBNST) to the nucleus accumbens (NAc). These findings illustrate the complexity with which juvenile isolation serves to negatively impact social behavior and identify a novel circuit through which animals integrate information about social state to orchestrate changes in social motivation.

neuroscience↗

bioRxiv2025

Activation of Toll and IMD pathways in the Drosophila brain following local and systemic bacterial infection

Brain infections are often life-threatening and have been linked to the development of neurodegenerative diseases. The fruit fly Drosophila melanogaster is a valuable experimental model to study immunity and the pathophysiology of brain infections. The exact cellular pathways through which brain-specific immune responses are mounted in Drosophila, however, remain poorly characterized. Here, we investigated how brain-specific or systemic infection with Micrococcus luteus and Escherichia coli bacteria activates the Drosophila NF-{kappa}B innate immune pathways Toll and immune deficiency (IMD) in the central nervous system of the fly. We tested the hypothesis that these pathways are acutely activated in the Drosophila brain, and that their activation persists over time, even if bacteria have been cleared. We demonstrate that in control genotypes, brain-specific bacterial infection leads to Drosomycin (Drs, Toll pathway) and Diptericin B (DiptB, IMD pathway) upregulation and that glia appear to be the primary cell type mounting this immune response at both early and later stages of infection, although some activation is observed in neurons as well. We show that the upregulation of Drs and DiptB expression also depends on canonical components of the Toll and IMD pathways, respectively. Interestingly, we found that systemic infection with M. luteus leads to brain-specific Drs activation and that signals from the fat body and hemocytes can activate the Toll pathway in the brain, pointing to an inter-organ communication. Together, these results contribute to our understanding of how non-lethal bacterial infections result in activation of NF-{kappa}B immunity in Drosophila brain that could potentially be targeted to prevent progression of neurodegeneration. HighlightsO_LIBrain immunity is induced following bacterial brain infection and depends on canonical NF-{kappa}B pathway components. C_LIO_LINF-{kappa}B signaling pathways are induced acutely and persist over time after bacterial brain infection. C_LIO_LIHost functional immunity clears bacteria in the brain post-bacterial brain infection. C_LIO_LIGlia are the main brain cell type in which NF-{kappa}B immunity is induced at both early and later stages of bacterial infection. C_LI

immunology↗

bioRxiv2024

SAUSI: a novel assay for measuring social anxiety and motivation

Social aversion is a key feature of numerous mental health disorders such as Social Anxiety and Autism Spectrum Disorders. Nevertheless, the biobehavioral mechanisms underlying social aversion remain poorly understood. Progress in understanding the etiology of social aversion has been hindered by the lack of comprehensive tools to assess social aversion in model systems. Here, we created a new behavioral task - Selective Access to Unrestricted Social Interaction (SAUSI), which integrates elements of social motivation, hesitancy, decision-making, and free interaction to enable the wholistic assessment of social aversion in mice. Using this novel assay, we found that social isolation-induced social aversion in mice is largely driven by increases in social fear and social motivation. Deep learning analyses revealed a unique behavioral footprint underlying the socially aversive state produced by isolation, demonstrating the compatibility of modern computational approaches with SAUSI. Social aversion was further assessed using traditional assays - including the 3-chamber sociability assay and the resident intruder assay - which were sufficient to reveal fragments of a social aversion phenotype, including changes to either social motivation or social interaction, but which failed to provide a wholistic assessment of social aversion. Critically, these assays were not sufficient to reveal key components of social aversion, including social freezing and social hesitancy behaviors. Lastly, we demonstrated that SAUSI is generalizable, as it can be used to assess social aversion induced by non-social stressors, such as foot shock. Our findings debut a novel task for the behavioral toolbox - one which overcomes limitations of previous assays, allowing for both social choice as well as free interaction, and offers a new approach for assessing social aversion in rodents.

neuroscience↗