Biology subjects

Patton, M. S.

Publications and source records attributed to Patton, M. S..

3 recordsLinked to original sources

bioRxiv2025

Microglial MyD88-dependent signaling influences extracellular matrix development and interneuron maturation in the hippocampus

Parvalbumin interneurons (PVIs) are disrupted across diverse neurodevelopmental disorders, highlighting their vulnerability to developmental perturbations. Inflammation can perturb PVI development and function, and inflammatory mechanisms are often propagated within the brain by microglia. Yet the microglial mechanisms linking inflammatory signals to interneuron development are unclear. To test the role of microglial innate immune signaling in PVI development, we used mice lacking toll-like receptor adaptor MyD88 specifically in microglia. MyD88-deficient microglia showed reduced inflammatory responses but increased early-life phagocytosis of inhibitory synaptic material. In adulthood, males without microglial MyD88 exhibited increased hippocampal PVI density, increased extracellular matrix (ECM) deposition, increased inhibitory signaling, and impaired discrimination behaviors. We determined the cytokine interleukin (IL)-33, which normally drives adult microglial remodeling of the ECM, is developmentally regulated in the hippocampus. MyD88-deficient microglia fail to respond to IL-33, leading to reduced remodeling of the ECM component aggrecan. These results reveal microglial immune signaling via MyD88 regulates hippocampal inhibitory circuit development in a sex-specific manner.

neuroscience↗

bioRxiv2025

Perineuronal Net and Inhibitory Synapse Remodeling on Striatal Fast-spiking Interneurons by Chronic Alcohol Exposure

Alcohol use disorder is characterized by persistent drinking in the face of negative consequences. Such inflexible drinking requires dorsolateral striatum fast-spiking interneurons, which comprise roughly 1% of all striatal neurons. How chronic ethanol exposure affects fast-spiking interneuron physiology is poorly understood. We discover in mice that chronic ethanol exposure induced a dramatic loss of GABAergic, but not glutamatergic, synapses onto dorsolateral striatum fast-spiking interneuron somata and proximal dendrites where perineuronal nets, a subdivision of the extracellular matrix, are enriched. We found that chronic ethanol exposure degraded these perineuronal nets and that enzymatically degrading perineuronal nets similarly reduced GABAergic transmission onto dorsolateral striatum fast-spiking interneurons. Modeling the effect of alcohol, we find that silencing extrinsic GABAergic projections to the dorsolateral striatum increased voluntary ethanol consumption. Taken together, these data suggest chronic alcohol exposure remodels perineuronal nets and inhibitory synapses on fast-spiking interneurons to facilitate alcohol drinking.

neuroscience↗

bioRxiv2022

Estradiol mediates stress-susceptibility in the male brain

In susceptible populations, stress is a major risk factor for the development of mental disorders, including depression. Estradiol, often considered a female hormone, is distributed in the male brain via aromatization of testosterone. The role of estrogen receptors (ERs) in male stress susceptibility and depression is not well understood. We found that absence of ER{beta} is associated with susceptibility to stress in male mice and that activity of ER{beta}-projecting neurons from the basolateral amygdala to nucleus accumbens is reduced in hypogonadal mice subjected to stress, while activation of this circuit reverses stress-induced maladaptive behaviors. We identified that absence of estradiol, but not testosterone per se, underlies stress susceptibility and that brain-selective delivery of estradiol prevents the development of depression-related behaviors. Our findings provide evidence for an estrogen-based mechanism underlying stress susceptibility and offer an unexpected therapeutic strategy for treating depression in males.

neuroscience↗