Biology subjects

Hentges, S. T.

Publications and source records attributed to Hentges, S. T..

5 recordsLinked to original sources

bioRxiv2026

Activity-based anorexia enhances glutamatergic synaptic transmission and neuronal excitability within the nucleus accumbens of female mice

Anorexia nervosa is a severe psychiatric disorder characterized by persistent food restriction and often excessive physical activity, implicating dysfunction in neural circuits governing motivation, reward, and behavioral persistence. The nucleus accumbens (NAc) is a central component of these circuits, yet synaptic and cellular adaptations within this region during anorexia-like states remain poorly defined. Using the activity-based anorexia (ABA) paradigm in adult female mice, we examined glutamatergic signaling and intrinsic neuronal properties in the NAc shell. ABA exposure produced rapid weight loss, reduced food intake, and progressively increased running-wheel activity. Biochemical analyses of NAc shell tissue revealed elevated membrane-associated GluA2 AMPA receptor protein. Consistent with this finding, whole-cell patch-clamp recordings from medium spiny neurons showed increased amplitude of spontaneous excitatory postsynaptic currents. ABA also enhanced intrinsic neuronal excitability, reflected by greater firing in response to depolarizing current injections. Together, these convergent biochemical and electrophysiological results demonstrate that ABA induces coordinated postsynaptic strengthening and increased intrinsic excitability in NAc shell medium spiny neurons. These adaptations suggest a sustained increase in accumbal output that may bias motivational circuit function and contribute to excessive activity and suppressed feeding during anorexia-like conditions, paralleling glutamatergic plasticity observed in other compulsive disorders, including substance use disorder.

neuroscience↗

bioRxiv2023

Sex-specific prefrontal-hypothalamic control of behavior and stress responding

Depression and cardiovascular disease are both augmented by daily life stress. Yet, the biological mechanisms that translate psychological stress into affective and physiological outcomes are unknown. Previously, we demonstrated that stimulation of the ventromedial prefrontal cortex (vmPFC) has sexually divergent outcomes on behavior and physiology. Importantly, the vmPFC does not innervate the brain regions that initiate autonomic or neuroendocrine stress responses; thus, we hypothesized that intermediate synapses integrate cortical information to regulate stress responding. The posterior hypothalamus (PH) directly innervates stress-effector regions and receives substantial innervation from the vmPFC. In the current studies, circuit-specific approaches examined whether vmPFC synapses in the PH coordinate stress responding. Here we tested the effects of optogenetic vmPFC-PH circuit stimulation in male and female rats on social and motivational behaviors as well as physiological stress responses. Additionally, an intersectional genetic approach was used to knock down synaptobrevin in PH-projecting vmPFC neurons. Our collective results indicate that male vmPFC-PH circuitry promotes positive motivational valence and is both sufficient and necessary to reduce sympathetic-mediated stress responses. In females, the vmPFC-PH circuit does not affect social or preference behaviors but is sufficient and necessary to elevate neuroendocrine stress responses. Altogether, these data suggest cortical regulation of stress reactivity and behavior is mediated, in part, by projections to the hypothalamus that function in a sex-specific manner.

neuroscience↗

bioRxiv2021

Ventral tegmental area glutamate neurons mediate the nonassociative consequences of traumatic stress

Exposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data implicate ventral tegmental area (VTA) glutamate neuronal activity as functionally important for signaling aversive or threating stimuli. However, it is unknown whether VTA glutamate neurons regulate transsituational outcomes that result from stress and whether these neurons are sensitive to stressor controllability. This work established an operant mouse paradigm to examine the impact of stressor controllability on VTA glutamate neuron function and stressor outcome. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance in male mice. Cell-type-specific calcium recordings showed that both controllable and uncontrollable stressors increased VTA glutamate neuronal activity. Chemogenetic reduction of VTA glutamate neuron activity prevented the behavioral sequelae of uncontrollable stress. Our results provide causal evidence that mice can be used to model stressor controllability and that VTA glutamate neurons may contribute to transsituational stressor outcomes, such as social avoidance and exaggerated fear that are observed within trauma-related disorders.

neuroscience↗

bioRxiv2020

Sexually divergent cortical control of affective-autonomic integration

Depression and cardiovascular disease reduce quality of life and increase mortality risk. These conditions commonly co-occur with sex-based differences in incidence and severity. However, the biological mechanisms linking the disorders are poorly understood. In the current study, we hypothesized that the infralimbic (IL) prefrontal cortex integrates mood-related behaviors with the cardiovascular burden of chronic stress. In a rodent model, we utilized optogenetics during behavior and in vivo physiological monitoring to examine how the IL regulates affect, social motivation, neuroendocrine-autonomic stress reactivity, and the cardiac consequences of chronic stress. Our results indicate that IL glutamate neurons increase socio-motivational behaviors specifically in males. IL activation also reduced endocrine and cardiovascular stress responses in males, while increasing reactivity in females. Moreover, prior IL stimulation protected males from subsequent chronic stress-induced sympatho-vagal imbalance and cardiac hypertrophy. Our findings suggest that cortical regulation of behavior, physiological stress responses, and cardiovascular outcomes fundamentally differ between sexes.

neuroscience↗

bioRxiv2018

Temporal dependence of shifts in mu opioid receptor mobility at the cell surface after agonist binding observed by single-particle tracking

Agonist binding to the mu opioid receptor (MOR) results in conformational changes that allow recruitment of G-proteins, activation of downstream effectors and eventual desensitization and internalization, all of which could affect receptor mobility. The present study employed single particle tracking (SPT) of quantum dot labeled FLAG-tagged MORs to examine shifts in MOR mobility after agonist binding. FLAG-MORs on the plasma membrane were in both mobile and immobile states under basal conditions. Activation of FLAG-MORs with DAMGO caused an acute increase in the fraction of mobile MORs, and free portions of mobile tracks were partially dependent on interactions with G-proteins. In contrast, 10-minute exposure to DAMGO or morphine increased the fraction of immobile FLAG-MORs. While the decrease in mobility with prolonged DAMGO exposure corresponded to an increase in colocalization with clathrin, the increase in colocalization was present in both mobile and immobile FLAG-MORs. Thus, no single mobility state of the receptor accounted for colocalization with clathrin. These findings demonstrate that SPT can be used to track agonist-dependent changes in MOR mobility over time, but that the mobility states observed likely arise from a diverse set of interactions and will be most informative when examined in concert with particular downstream effectors.

neuroscience↗