Biology subjects

Deming, M.

Publications and source records attributed to Deming, M..

3 recordsLinked to original sources

bioRxiv2026

Mesohabenular glutamatergic regulation of the consequences of uncontrollable stress

Perceived or volitional control over a stressor is a critical determinant of resilient versus susceptible behavioral phenotypes. Activation of the lateral habenula (LHb) is required for the behavioral changes or "learned helplessness" effects that follow inescapable, but not escapable, stress. However, the relevant LHb inputs that regulate its mediation of inescapable stress outcomes are not fully elucidated. We find that ventral tegmental area (VTA) glutamatergic axons in LHb are activated by aversive stimuli, and this activation was not altered by prior inescapable stress experience. Similarly, optogenetic activation of VTA glutamatergic axons in LHb resulted in c-Fos expression in LHb neurons that did not depend on a prior inescapable stress experience. Photoinhibition of VTA glutamatergic axons in LHb during each inescapable stress trial prevented social and nonsocial consequences of inescapable stress. We interpret these results such that VTA glutamatergic inputs to LHb report aversive stimuli to LHb, possibly related to current salient aversive experience without regard to prior stress history. Nevertheless, VTA glutamatergic input to the LHb plays an important role in regulating LHb-mediated social and nonsocial consequences of uncontrollable stress.

neuroscience↗

bioRxiv2025

Assessing the role of BNST GABA neurons in backward conditioned suppression

Conditioned suppression is a useful paradigm for measuring learned avoidance. In most conditioned suppression studies, forward conditioning is used where a cue predicts an aversive stimulus. However, backward conditioning, in which an aversive stimulus predicts a cue, provides unique insights into learned avoidance due to its influence on both conditioned excitation and inhibition. We trained mice to consume sucrose in context A, associated an aversive stimulus in context B to few or many forward or backwards paired cues (CS+), and then tested for conditioned suppression in context A in response to the CS+. We found that few or many forward CS+ and few backward CS+ produced conditioned suppression, but many backwards cues did not. Administration of diazepam, a positive allosteric modulator of the GABA-A receptor, prevented conditioned suppression to the backward CS+ but not to the forward CS+. Furthermore, freezing behavior was observed in response to the forward CS+ but not the backward CS+, and diazepam had no effect on freezing or locomotion. We next examined BNST GABA neurons for potential sensitivity to backwards cues and conditioned suppression. VGaT BNST signaling increased in response to sucrose licks during the backward CS+ but not to licks outside the CS+ and not to the backward CS+ onset or offset. Using designer receptors, we found that BNST VGaT neuron activation, but not its inhibition, prevented backward conditioned suppression expression. We conclude that backward conditioned suppression is dependent on both positive allosteric modulation of GABA on GABA-A receptors by diazepam and BNST GABA neurons.

neuroscience↗

bioRxiv2021

Mucosal and systemic responses to SARS-CoV-2 vaccination in infection naive and experienced individuals

With much of the world infected with or vaccinated against SARS-CoV-2, understanding the immune responses to the SARS-CoV-2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS-CoV-2 mRNA vaccines in 62 individuals with and without prior SARS-CoV-2 exposure that were divided into three groups based on serostatus and/or degree of symptoms: Antibody negative, Asymptomatic, and Symptomatic. In the previously SARS-CoV-2-infected (SARS2-infected) Asymptomatic and Symptomatic groups, symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG levels peaked after 1st vaccination in the SARS2-infected groups, and were higher that the in the SARS2-naive group in the plasma and nasal samples at all time points. Neutralizing antibodies titers were also higher against the WA-1 and B.1.617.2 (Delta) variants of SARS-CoV-2 in the SARS2-infected compared to SARS2-naive vaccinees. After the first vaccination, differences in cellular immunity were not evident between groups, but the AIM+ CD4+ cell response correlated with durability of humoral immunity against the SARS-CoV-2 S protein. In those SARS2-infected, the number of vaccinations needed for protection, the durability, and need for boosters are unknown. However, the lingering differences between the SARS2-infected and SARS2-naive up to 10 months post-vaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naive vaccinees) are needed to narrow the differences observed between these groups.

immunology↗