Biology subjects

Soma, K. K.

Publications and source records attributed to Soma, K. K..

10 recordsLinked to original sources

bioRxiv2026

A Novel Operant Conditioning Task to Assess Motivation to Exercise in Rats

Voluntary physical activity is a highly motivated behavior with important implications for physical and mental health, yet the neural and endocrine mechanisms underlying motivation to exercise remain poorly understood. In contrast, motivation for sugar/palatable foods, drugs, and sex has been extensively characterized using operant paradigms. Here, we describe a novel progressive ratio operant task to measure motivation to run, independent of running ability. Using female Long Evans rats, which exhibit robust voluntary running behavior, we validated this paradigm by applying a manipulation well known to enhance the motivation to run: calorie restriction. Calorie-restricted animals exhibited increased operant responding to gain access to a running wheel, thus demonstrating heightened motivation for exercise. More specifically, calorie-restricted rats completed more ratios, reached a higher breakpoint in the progressive ratio task, ran more, and spent more time in the operant chamber. We did not observe any effects of calorie restriction on the estrous cycle or steroids (e.g. corticosterone, testosterone) in the blood or brain. Importantly, our task dissociates the motivational drive for physical activity from the ability to perform the physical activity itself, providing a new paradigm for studying the neural and endocrine mechanisms that regulate exercise motivation.

animal behavior and cognition↗

bioRxiv2025

A bifunctional optical reporter for tracking estrogen response dynamics in neurons

Estrogens are inherently dynamic signaling molecules whose fluctuations induce profound shifts in physiology and behavior. However, methods for tracking the dynamics of estrogen action in vivo are limited and not tissue-specific, making it difficult to directly relate dynamics to ongoing physiological, behavioral, and neural changes. Traditionally, estrogen sensitive cells have been identified by metrics such as receptor expression or radioactive ligand binding, but these measures do not capture the dynamic nature of hormone response. In addition, current methods for assessing the dynamics of estrogens in an individual, including microdialysis and vaginal cytology, lack temporal and spatial resolution.To address this need we developed a bifunctional reporter called neuro-seeER (neuronal see Estrogen Response) that can be used to track changes in exogenous and endogenous estrogen dynamics in vitro and in vivo, including longitudinally in behaving animals. We confirmed that the fluorescent response requires estrogen receptor expression, is specific to activation with estradiol, and is consistent with the timescale of transcriptional induction. Neuro-seeER expression in the hypothalamus of Esr1-Cre mice revealed dynamic labeling of estrogen-responsive cells following treatment with exogenous estradiol, and fluorescence-aided cell sorting followed by RNA-sequencing confirmed that high neuro-seeER response is associated with enriched expression of genes associated with endogenous estrogen responses. Using a novel "snapshot" photometry method to track the dynamics longitudinally in vivo, we demonstrate that we can robustly detect exogenous estrogen response across multiple hypothalamic sites simultaneously. Finally, we demonstrate that this tool is uniquely suited to capturing endogenous estrogen response dynamics in vivo across the long timescale of the estrous cycle, revealing individual differences in neural estrogen dynamics. Together, these findings reveal unexpected cellular and temporal heterogeneity of the transcriptional response and demonstrate the feasibility of tracking the dynamics of hormonal response alongside additional neural, cell signaling, or behavioral measures.

neuroscience↗

bioRxiv2025

Seasonal plasticity in neuroendocrine mechanisms relevant to year-round territorial aggression in a wild teleost fish

Animals experience cyclical environmental changes, such as seasons, that require physiological adjustments to support different behaviors. Although many behaviors occur only during specific periods, some species, like Gymnotus omarorum, display territorial aggression year-round, making them valuable models to study seasonal plasticity in the mechanisms maintaining stable behavioral outputs. G. omarorum is a teleost fish in which neuroestrogens have been shown to play a key role in non-breeding aggression. Here, we quantified circulating hormone levels and gene expression in the social behavior network of wild breeding and non-breeding individuals. During the non-breeding season, both sexes exhibited elevated circulating androgen levels, providing potential substrates for local estrogen synthesis. Consistently, brain aromatase and estrogen receptor expression were also upregulated, suggesting an increased capacity for local estrogen synthesis and signaling. Our findings provide the first evidence in a teleost of seasonal plasticity in the mechanisms underlying territorial aggression. Comparisons with birds and mammals reveal both shared and lineage-specific strategies, highlighting common endocrine principles while revealing the evolutionary diversity of solutions to maintain a stable behavioral phenotype across changing seasonal contexts.

neuroscience↗

bioRxiv2025

Maternal sucrose intake during pregnancy alone disrupts testosterone and allopregnanolone levels in the fetal brain of rats

BackgroundIntake of added sugars, such as sucrose, is high globally. In rats, a maternal high-sucrose diet (HSD) from 10 wk before pregnancy to embryonic day (E)19.5 has widespread impacts on maternal, placental, and fetal blood and brain steroid levels, including glucocorticoids, androgens, and aldosterone. ObjectiveThis study examined whether maternal HSD during pregnancy alone is sufficient to alter maternal, placental, and fetal steroids. MethodsPregnant rats received either a control diet (1% kcal sucrose) or an isocaloric, nutrient-matched HSD (26% kcal sucrose) between E0.5-19.5. On E19.5, we collected maternal serum, placenta, fetal blood and brain, and amniotic fluid. We microdissected the placenta and fetal brain and measured 14 steroids using highly sensitive and specific liquid chromatography-tandem mass spectrometry (n=12-15/diet/sex). ResultsMaternal HSD during pregnancy alone did not alter maternal food intake, maternal body mass, and litter size (all p values [≥] 0.29, Students t-test) but increased the percentage of males in a litter (p = 0.03, Students t-test). Maternal HSD did not alter steroids in the maternal serum (all p values [≥] 0.21, Students t-test), placenta (all p values [≥] 0.07, 2-way analysis of variance (ANOVA)), and fetal blood (all p values [≥] 0.13, 2-way ANOVA). Nonetheless, maternal HSD increased testosterone in the fetal nucleus accumbens (p = 0.04, 2-way ANOVA), decreased allopregnanolone in the fetal amygdala (p = 0.01, 2-way ANOVA), and decreased 11-dehydrocorticosterone in the amniotic fluid (p = 0.05, 2-way ANOVA). ConclusionsMaternal HSD during pregnancy alone does not affect steroid levels in the maternal serum, placenta, or fetal blood, but disrupts testosterone and allopregnanolone levels in critical regions of the fetal brain that regulate reward-seeking and emotion. Thus, while a long-term maternal HSD is necessary for widespread endocrine effects, the fetal brain is sensitive to short-term increases in maternal sucrose consumption during pregnancy.

neuroscience↗

bioRxiv2025

Unexpected mechanisms of sex-specific memory vulnerabilities to acute traumatic stress

It is increasingly recognized that severe acute traumatic events (e.g., mass shooting, natural disasters) can provoke enduring memory disturbances, and these problems are more common in women. We probed the fundamental sex differences underlying memory vulnerability to acute traumatic stress (ATS), focusing on the role of the sex hormone, estrogen (17{beta}-estradiol) and its receptor signaling in hippocampus. Surprisingly, high physiological hippocampal estrogen levels were required for ATS-induced episodic memory disruption and the concurrent sensitization and generalization of fear memories in both male and female mice. Pharmacological and transgenic approaches demonstrated signaling via estrogen receptor (ER) in males and, in contrast, ER{beta} in females, as the mechanisms for these memory problems. Finally, identify distinct hippocampal chromatin states governed by sex and estrogen levels, which may confer an enduring vulnerability to post-traumatic memory disturbances in females.

neuroscience↗

bioRxiv2024

Prenatal glyphosate exposure disrupts the gut-brain axis across several generations in mice.

Glyphosate, a widely used herbicide in North America, has become prevalent in the food supply, raising concerns about potential health impacts. In this exploratory study, male and female F0 mice were exposed to glyphosate through drinking water during mating and gestation. We investigated whether prenatal exposure at dietary-relevant levels (0.01 mg/kg/day, Average American Diet, [AAD]) or the U.S. EPAs acceptable daily intake (1.75 mg/kg/day, [EPA upper limit]) altered gut, metabolic, and behavioral outcomes across two generations in mice with or without genetic susceptibility to colitis (Muc2+/- and Muc2-/-, respectively). Healthy (Muc2+/-) offspring of glyphosate-exposed mice exhibited colonic goblet cell depletion, reduced mucin-2 expression, and pro-inflammatory cytokine profiles in both F1 and F2 generations. These healthy (Muc2+/-) offspring also developed metabolic dysfunction, including impaired glucose tolerance, insulin resistance, and reduced GLP-1 in serum. Behavioral deficits were also observed in healthy (Muc+/-) mice including reduced locomotion and working memory, and these changes were associated with altered microbiome composition and gut-brain mediators. These findings suggest that prenatal glyphosate exposure, even below regulatory thresholds, may disrupt multiple physiological systems across generations, highlighting the need for further research and regulatory consideration.

pharmacology and toxicology↗

bioRxiv2024

Early life intestinal inflammation alters gut microbiome, impairing gut-brain communication and reproductive behavior in mice

Despite recent advances in understanding the connection between the gut microbiota and the adult brain, there remains a wide knowledge gap in how gut inflammation impacts brain development. We hypothesized that intestinal inflammation in early life would negatively affect neurodevelopment through dysregulation of microbiota communication to the brain. We therefore developed a novel pediatric chemical model of inflammatory bowel disease (IBD), an incurable condition affecting millions of people worldwide. IBD is characterized by chronic intestinal inflammation, and has comorbid symptoms of anxiety, depression and cognitive impairment. Significantly, 25% of patients with IBD are diagnosed during childhood, and the effect of chronic inflammation during this critical period of development is largely unknown. This study investigated the effects of early-life gut inflammation induced by DSS (dextran sulfate sodium) on a range of microbiota, endocrine, and behavioral outcomes, focusing on sex-specific impacts. DSS-treated mice exhibited increased intestinal inflammation, altered microbiota membership, and changes in microbiota-mediated circulating metabolites. The majority of behavioral measures were unaffected, with the exception of impaired mate-seeking behaviors in DSS-treated males. DSS-treated males also showed significantly smaller seminal vesicles, lower circulating androgens, and decreased intestinal hormone-activating enzyme activity. In the brain, microglia morphology was chronically altered with DSS treatment in a sex-specific manner. The results suggest that early-life gut inflammation causes changes in gut microbiota composition, affecting short-chain fatty acid (SCFA) producers and glucuronidase (GUS) activity, correlating with altered SCFA and androgen levels. The findings emphasize the developmental sensitivity to inflammation-induced changes in endocrine signalling and underscore long-lasting physiological and microbiome changes associated with juvenile IBD. HighlightsEarly-life gut inflammation produces sex-specific effects on i) microbiome, ii) sex hormones and iii) behaviour. Both sexes show disrupted gut bacterial members that regulate sex hormone levels. Male mice demonstrate deficits in mate seeking, which may be mediated by reduced androgen levels. Both male and female mice demonstrate shifts in hippocampal microglial morphology.

neuroscience↗

bioRxiv2023

Maternal high-sucrose consumption increases maternal and fetal glucocorticoids and decreases fetal androgens in the rat

Maternal diet has long-term effects on offspring brain development and behavior. Sucrose (table sugar) intakes are high in modern diets, but it is not clear how a maternal high-sucrose diet (HSD) affects the offspring. In rats, a maternal HSD (26% of calories from sucrose, which is human-relevant) alters maternal metabolism and brain and also alters adult offspring endocrinology and behavior in a sex-specific manner. Maternal sucrose intake increases corticosterone levels in adult female offspring and increases motivation for a sugar reward in adult male offspring. Here, to identify possible underlying mechanisms, we examined how a maternal HSD affects steroids in the dam, placenta, and fetus at embryonic day 19.5 using liquid chromatography tandem mass spectrometry. Maternal sucrose intake increased glucocorticoids (11-deoxycorticosterone and 11-dehydrocorticosterone) and tended to increase the mineralocorticoid aldosterone in maternal serum. In the placenta, maternal sucrose intake decreased androstenedione and testosterone. Maternal HSD increased aldosterone in the fetal blood. Similarly, in the fetal brain, maternal high-sucrose intake increased aldosterone in the medial prefrontal cortex and nucleus accumbens, decreased testosterone in the nucleus accumbens, and decreased corticosterone in the orbital cortex. In addition, the 11-dehydrocorticosterone/corticosterone and aldosterone/corticosterone ratios were increased in most examined brain regions. Lastly, maternal HSD increased 11-dehydrocorticosterone and aldosterone in the amniotic fluid. In summary, we found dramatic and widespread changes in maternal, placental, and fetal steroids that might mediate the long-term effects of maternal sucrose consumption on adult offspring neuroendocrinology and behavior.

neuroscience↗

bioRxiv2023

Brain and circulating steroids in an electric fish: relevance for non-breeding aggression

Steroids play a crucial role in modulating brain and behavior. While traditionally it is considered that the brain is a target of peripheral hormones produced in endocrine glands, it has been discovered that the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in brain regions involved in the regulation of social behaviors and can act locally regulating behaviors like reproduction and aggression. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain. We use the weakly electric fish Gymnotus omarorum, a species which shows non-breeding aggression in both sexes, to characterize these hormonal profiles in wild non-breeding adults. We show that: 1) systemic steroids in the non-breeding season are similar in both sexes, although only males have circulating 11-KT, 2) brain steroid levels are sexually dimorphic, as females display higher levels of AE, T and E1, and only males had 11-KT, 3) systemic androgens such as AE and T in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data fall in line with previous reports in G. omarorum which show that non-breeding aggression is dependent on the estrogenic pathway, as has also been shown in bird and mammal models. Overall, our results constitute a fundamental groundwork to understanding the complexity of hormonal modulation, its potential sex differences, the role of neurosteroids and the interplay between central and peripheral hormones in the regulation of behaviors.

neuroscience↗

bioRxiv2021

Androgen synthesis inhibition but not gonadectomy reduces persistence during strategy set-shifting and reversal learning in male rats

Androgens regulate behavioural flexibility, which is essential to adapt to a changing environment and depends on the medial prefrontal cortex (mPFC). Testosterone (T) administration decreases behavioural flexibility. It is well known that T is produced in the gonads, but T is also produced in the mesocorticolimbic system, which modulates behavioural flexibility. It is unclear how T produced in the brain versus the gonads influences behavioural flexibility. Here, we assess the effects of the androgen synthesis inhibitor abiraterone acetate (ABI) and long-term gonadectomy (GDX) on behavioural flexibility in two paradigms. In Experiment 1, ABI independent of GDX reduced the number of trials to criterion and perseverative errors in a strategy set-shifting task. Similarly, in Experiment 2, ABI but not GDX reduced perseverative errors in a reversal learning task. In subjects from Experiment 1, we also examined tyrosine hydroxylase immunoreactivity (TH-ir), and ABI but not GDX increased TH-ir in the mPFC. Our findings suggest that neurally-produced androgens modulate behavioural flexibility via modification of dopamine signalling in the mesocorticolimbic system. These results suggest novel roles for neurosteroids and possible side effects of ABI treatment for prostate cancer.

neuroscience↗