@article {157496, title = {Social dominance in rats is a determinant of susceptibility to stress.}, journal = {Proc Natl Acad Sci U S A}, volume = {122}, year = {2025}, month = {2025 May 13}, pages = {e2412314122}, abstract = {

Establishing a dominance hierarchy in social organisms is important for access to resources. Stress has been proposed as a major factor influencing an animal{\textquoteright}s likely position in a social hierarchy. Although individual differences in vulnerability to stress are increasingly recognized, how social hierarchy affects vulnerability remains relatively understudied. Here, we examined how the social dominance status of adult male Sprague-Dawley rats influences their response to stress in interactions with a familiar animal living in the same cage, and separately when confronting an unfamiliar rat of uncertain dominance status from another cage, using the tube test. Having determined the relatively stable within-cage social dominance status of animals, half were subjected to a single episode of 2-h immobilization stress. Cagemates, both control and stressed rats, again faced one another 1 d and 10 d after stress. First, the predetermined hierarchical rank among familiar cagemates was relatively unaffected by stress. However, second, the same stress had a differential impact in competitions between unfamiliar rats. Socially dominant control rats continued to win competitions but subordinate control rats, that had previously lost, sometimes started to win against previously dominant rats that had been stressed. Strikingly, subordinate stressed rats displayed consistent submissive-like behavior and they alone showed differential effects on dendritic spine density in the amygdala. Thus, an individual{\textquoteright}s social rank can influence its response to stress, an effect that is detectable in interactions with unfamiliar animals. These findings provide an additional dimension to animal models of stress used for exploring facets of social anxiety and withdrawal in stress-related psychiatric disorders.

}, keywords = {dominance; stress; structural plasticity; susceptibility; tube test.}, issn = {1091-6490}, doi = {10.1073/pnas.2412314122}, url = {https://www.pnas.org/doi/10.1073/pnas.2412314122?url_ver=Z39.88-2003\&rfr_id=ori\%3Arid\%3Acrossref.org\&rfr_dat=cr_pub++0pubmed}, author = {Srinivasan, Durga J and Kapgal, Vijayakumar and Morris, Richard G M and Chattarji, Sumantra} } @article {78161, title = {Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns.}, journal = {Mol Autism}, volume = {11}, year = {2020}, month = {2020 Jun 19}, pages = {52}, abstract = {

BACKGROUND: Fragile X syndrome (FXS), a neurodevelopmental disorder, is a leading monogenetic cause of intellectual disability and autism spectrum disorder. Notwithstanding the extensive studies using rodent and other pre-clinical models of FXS, which have provided detailed mechanistic insights into the pathophysiology of this disorder, it is only relatively recently that human stem cell-derived neurons have been employed as a model system to further our understanding of the pathophysiological events that may underlie FXS. Our study assesses the physiological properties of human pluripotent stem cell-derived cortical neurons lacking fragile X mental retardation protein (FMRP).

METHODS: Electrophysiological whole-cell voltage- and current-clamp recordings were performed on two control and three FXS patient lines of human cortical neurons derived from induced pluripotent stem cells. In addition, we also describe the properties of an isogenic pair of lines in one of which FMR1 gene expression has been silenced.

RESULTS: Neurons lacking FMRP displayed bursts of spontaneous action potential firing that were more frequent but shorter in duration compared to those recorded from neurons expressing FMRP. Inhibition of large conductance Ca-activated K currents and the persistent Na current in control neurons phenocopies action potential bursting observed in neurons lacking FMRP, while in neurons lacking FMRP pharmacological potentiation of voltage-dependent Na channels phenocopies action potential bursting observed in control neurons. Notwithstanding the changes in spontaneous action potential firing, we did not observe any differences in the intrinsic properties of neurons in any of the lines examined. Moreover, we did not detect any differences in the properties of miniature excitatory postsynaptic currents in any of the lines.

CONCLUSIONS: Pharmacological manipulations can alter the action potential burst profiles in both control and FMRP-null human cortical neurons, making them appear like their genetic counterpart. Our studies indicate that FMRP targets that have been found in rodent models of FXS are also potential targets in a human-based model system, and we suggest potential mechanisms by which activity is altered.

}, issn = {2040-2392}, doi = {10.1186/s13229-020-00351-4}, author = {Das Sharma, Shreya and Pal, Rakhi and Reddy, Bharath Kumar and Selvaraj, Bhuvaneish T and Raj, Nisha and Samaga, Krishna Kumar and Srinivasan, Durga J and Ornelas, Loren and Sareen, Dhruv and Livesey, Matthew R and Bassell, Gary J and Svendsen, Clive N and Kind, Peter C and Chandran, Siddharthan and Chattarji, Sumantra and Wyllie, David J A} }