Biology subjects

Gilman, L. M.

Publications and source records attributed to Gilman, L. M..

2 recordsLinked to original sources

bioRxiv2025

PMAT enhances sexual dimorphism of fear behaviors and facilitates female mice's generalized contextual fear extinction

Enhanced signaling of dopamine and/or serotonin during highly arousing situations can be reduced or terminated by monoamine transporters. One such transporter, plasma membrane monoamine transporter (PMAT, Slc29a4), attenuates both dopamine and serotonin signaling. An absence of selective pharmacological inhibitors means genetically modified mice constitutively deficient in PMAT remain the best tool with which to study PMATs organism-level functional effects. Fear conditioning is a high arousal process. Generalization of fear is an evolutionarily advantageous process, whereby information learned from one experience is applied to other new but similar encounters. Pathological fear generalization, in contrast, is a core feature of most anxiety disorders. Given our previous findings indicating PMAT function reduces male mices context fear and enhances extinction of female mices cued fear, we hypothesized that PMAT would similarly reduce generalization (i.e., enhance discrimination) of context and cued fear in male and female mice, respectively. Our context and cued fear conditioning experiments in adult PMAT wildtype (+/+) and heterozygous (+/-) male and female mice partially supported our hypotheses. We discovered PMAT functions to facilitate extinction of contextually generalized fear, plus subsequent extinction of context-specific fear, selectively in females. Moreover, when specific fear cues or contexts were temporally presented before cues or contexts that were similar enough to make generalization possible, PMAT enhanced biological sex differences. Growing evidence reports common PMAT polymorphisms elicit measurable effects when PMAT function is reduced. Thus, we suspect future experiments may reveal positive associations between PMAT polymorphisms and risk for anxiety disorder symptoms, particularly in people assigned female at birth. Inclusion of these genetic variations in pharmacogenomic analyses may prove therapeutically beneficial.

neuroscience↗

bioRxiv2025

Voluntary eating of saltier food by mice and acute stress each abrogate reductions in a neuroinflammatory marker across sexes

Both consuming excess salt (NaCl) and experiencing environmental stress can elevate neuroinflammation and enhance risk for non-communicable diseases. Most rodent studies investigating these topics use only males, and assess salt or stress separately. Here, we used adult female and male mice to investigate how the combination of access to food high in salt (4% NaCl, w/w) and experiencing an acute stressor interact to affect levels of a proxy measure for neuroinflammation (Iba1). We hypothesized eating salty food and experiencing stress would each individually augment neuroinflammation, and their combination would be additive. Further, we anticipated salty food consumption would increase active stress coping behaviors, and that all of these effects would be enhanced in female mice. Over 4 or 8 weeks, we further evaluated how mice responded to choice access to low (0.4%) and high salt food simultaneously. Our hypothesis that mice across sexes would eventually prefer high over low salt food was supported, while our expectations regarding neuroinflammation and stress did not consistently align with our findings. Instead, we found modest changes in passive coping behaviors driven by our choice condition, unanticipated reductions in sham stress neuroinflammation by high salt in brain region- and biological sex-specific patterns after 4 weeks, and distinct sex- and salt-selective increases in swim stress neuroinflammation after 8 weeks. Though some of our results were unexpected, they include multiple novel and translationally relevant outcomes. Mice willingly choose to eat saltier food over time, akin to people, and this could sex-specifically decrease (females) or augment (males) passive coping stress strategies while eliciting distinctive stress- and brain region-dependent neuroinflammatory patterns over time. Future studies implementing more complex behavior tests and stress manipulations will advance identification of the hidden ways through which salty food and stressful experiences interact to affect risk for non-communicable diseases.

neuroscience↗