Biology subjects

Vaidyanathan, T. V.

Publications and source records attributed to Vaidyanathan, T. V..

3 recordsLinked to original sources

bioRxiv2026

Maternal high-fat diet drives sex-specific microglia remodeling of serotonergic reward circuits

Maternal nutrition shapes offspring brain development and influences neurodevelopmental disorder risk, but the underlying mechanisms remain unclear. In mice, maternal high-fat diet exposure disrupted microglia-serotonin interactions during a critical postnatal period, producing persistent, sex-specific mesolimbic alterations. Male but not female offspring showed increased serotonergic fiber density in the nucleus accumbens (NAc), coincident with reduced microglial phagocytosis of serotonergic projections. Microglial 5-HT2C receptor signaling is a key regulator of this process. Viral over expression in microglia, mimicking diet-induced upregulation, was sufficient to cause serotonergic hyperinnervation. By adulthood, male offspring displayed increased NAc serotonin release and projection-specific changes in dorsal raphe physiology. These circuit alterations accelerated reward-motivated learning, a phenotype reproduced by chemogenetic activation of NAc-projecting serotonergic neurons. Together, these findings reveal a novel mechanism by which maternal diet programs serotonergic circuit assembly and behavior in a sex-specific manner, providing a potential link between early-life metabolic inflammation and lifelong serotonergic dysfunction.

neuroscience↗

bioRxiv2025

Prenatal exposure to environmental stressors alters gut macrophage development and gastrointestinal function of male offspring

Gastrointestinal (GI) dysfunction is a frequently reported comorbidity of neurodevelopmental disorders (NDDs). Early-life inflammatory challenges from the environment (e.g. infection, toxicants) can increase risk for NDDs but the impact of such stressors on the developing GI tract is not well understood. We investigated possible mechanisms by which GI comorbidities occur in response to environmental stressors using our well-characterized model of combined gestational exposure to air pollution (diesel exhaust particles, DEP) and maternal stress (MS), which induces social deficits in male but not female offspring. We show that DEP/MS disrupts normal GI development, leading to altered small intestine morphology in neonatal males, but not females. Recent evidence shows that resident macrophages of the gut prune enteric neurons during a precise postnatal window. We found decreased pruning of gut enteric neurons by the resident macrophages of the muscularis externa in DEP/MS exposed males at postnatal day 14. In line with this, we saw the expression of motor neuron-associated genes spike in males at the same postnatal time point following DEP/MS exposure. Finally, we assessed the motor function of the GI tract of these animals and observed dysmotility in DEP/MS males only. Taken together, these findings establish intestinal macrophages as a mediator of GI development that is sensitive to early-life perturbations from the environment, highlighting a potential mechanism connecting NDDs with comorbid GI dysfunction.

developmental biology↗

bioRxiv2022

Astrocytic Gi-GPCR activation enhances stimulus-evoked extracellular glutamate

Astrocytes perform critical functions in the nervous system, many of which are dependent on neurotransmitter-sensing through G protein-coupled receptors (GPCRs). However, whether specific astrocytic outputs follow specific GPCR activity remains unclear, and exploring this question is critical for understanding how astrocytes ultimately influence brain function and behavior. We previously showed that astrocytic Gi-GPCR activation is sufficient to increase slow-wave neural activity (SWA) during sleep when activated in cortical astrocytes1. Here, we investigate the outputs of astrocytic Gi-GPCRs, focusing on the regulation of extracellular glutamate and GABA, by combining in vivo fiber photometry recordings of the extracellular indicators iGluSnFR and iGABASnFR with astrocyte-specific chemogenetic Gi-GPCR activation. We find that Gi-GPCR activation does not change spontaneous dynamics of extracellular glutamate or GABA. However, Gi-GPCR activation does specifically increase visual stimulus-evoked extracellular glutamate. Together, these data point towards a complex relationship between astrocytic inputs and outputs in vivo that may depend on behavioral context. Further, they suggest an extracellular glutamate-specific mechanism underlying some astrocytic Gi-GPCR-dependent behaviors, including the regulation of sleep SWA.

neuroscience↗