Biology subjects

Snyder, A. E.

Publications and source records attributed to Snyder, A. E..

3 recordsLinked to original sources

bioRxiv2021

The vagus nerve is critical for regulation of hypothalamic-pituitary-adrenal axis responses to acute stress

The hypothalamic pituitary adrenal (HPA) axis is a critical regulator of physiologic and psychological responses to acute and chronic stressors. HPA axis function is control by numerous feedback inhibitory mechanisms, disruptions of which can lead to various psychiatric conditions, such as depression, posttraumatic stress disorder, and schizophrenia. Vagus nerve stimulation has been shown to be efficacious in the treatment of in these various mental health issues potentially via modulation of HPA axis function, but the mechanisms by which the vagus nerve may regulate HPA function has not been fully elucidated. In the present studies, we sought to test the hypothesis that the vagus nerve is a critical regulator of HPA function. Neuroendocrine function and neurocircuit changes in corticotropin releasing factor (CRF) neurons in the paraventricular nucleus of the hypothalamus (PVN) were examined following acute stress after subdiaphragmatic left vagotomy (VX) in adult male Sprague-Dawley rats. We found that VX mimics HPA activation seen in sham surgery animals exposed to acute restraint stress, particularly increased plasma corticosterone levels, elevated PVN CRF mRNA, and increased action potential firing of putative CRF neurons in PVN brain slices. Furthermore, VX animals exposed to acute restraint stress showed increased elevations of plasma corticosterone and PVN CRF mRNA which may be due to lack of compensatory PVN GABAergic signaling in response to acute stress. Both Sham/Stress and VX/no stress conditions increased action potential firing in putative PVN CRF neurons, but this effect was not seen in the VX/stress condition, suggesting that not all forms of stress compensation are lost following VX. Overall, these findings suggest that the vagus nerve may play a critical role in regulating HPA axis function via modulation of local PVN neurocircuit activity.

neuroscience↗

bioRxiv2018

Chronic intermittent ethanol and acute stress similarly modulate BNST CRF neuron activity via noradrenergic signaling

Relapse is a critical barrier to effective long-term treatment of alcoholism, and stress is often cited as a key trigger to relapse. Numerous studies suggest that stress-induced reinstatement to drug seeking behaviors is mediated by norepinephrine (NE) and corticotropin releasing factor (CRF) signaling interactions in the bed nucleus of the stria terminalis (BNST), a brain region critical to many behavioral and physiologic responses to stressors. Here we sought to directly examine the effects of NE on BNST CRF neuron activity and determine if these effects may be modulated by chronic intermittent EtOH (CIE) exposure or a single restraint stress. Utilizing whole-cell patch clamp electrophysiological techniques in CRF-tomato reporter mice, we found that NE depolarized BNST CRF neurons in naive mice in a {beta}-adrenergic receptor (AR) dependent mechanism. CRF neurons from CIE or stress-exposed mice had significantly elevated basal resting membrane potential compared to naive mice. Furthermore, CIE and stress individually disrupted the ability of NE to depolarize CRF neurons, suggesting that both stress and CIE utilize {beta}-AR signaling to modulate BNST CRF neurons. Neither stress nor CIE altered the ability of exogenous NE to inhibit evoked glutamatergic transmission onto BNST CRF neurons, a mechanism previously shown to be -AR dependent. Altogether these findings suggest that stress and CIE interact with {beta}-AR signaling to modulate BNST CRF neuron activity, potentially disrupting the /{beta}-AR balance of BNST CRF neuronal excitability. Restoration of /{beta}-AR balance may lead to novel therapies for the alleviation of many stress-related disorders.

neuroscience↗

bioRxiv2018

Access schedules mediate the impact of high fat diet on ethanol intake in mice.

Alcoholism and high fat diet (HFD)-induced obesity individually promote insulin resistance and glucose intolerance in clinical populations, increasing risk for metabolic diseases. Conversely, animal studies, typically utilizing forced/continuous alcohol (EtOH) access, tend to show that EtOH intake mitigates HFD-induced effects on insulin and glucose function, while HFD decreases voluntary EtOH intake in continuous access models. However, the impact of HFD on intermittent EtOH intake and resultant changes to metabolic function are not well characterized. The present studies sought to determine if HFD alters EtOH intake in male C57Bl/6J mice given differing two-bottle choice EtOH access schedules, and to assess resultant impact on insulin sensitivity and glucose tolerance. In the first experiment, mice had Unlimited Access EtOH (UAE)+HFD (n=15; HFD=60% calories from fat, 10% EtOH v/v, ad libitum) or UAE+Chow (n=15; control diet=16% calories from fat, ad libitum) for 6 weeks. UAE+HFD mice had lower EtOH preference, consumed significantly less EtOH, and were insulin resistant and hyperglycemic compared with UAE+Chow mice. In the second experiment, mice had Limited Access EtOH (LAE, 4 hrs/d; 3 d/wk)+HFD (n=15) or LAE+Chow (n=15) with increasing EtOH concentrations (10%, 15%, 20%). LAE+HFD mice had no difference in total EtOH consumption compared to LAE+Chow mice, but exhibited hyperglycemia, insulin resistance, and glucose intolerance. In the third experiment, mice had intermittent HFD access (single 24 hr session/week) with limited access to EtOH (iHFD-E, 4hrs/d; 4 d/wk) (n=10). iHFD-E mice displayed binge eating behaviors and consumed significantly more EtOH than mice given ad libitum chow or HFD, suggesting transfer of binge eating to binge drinking behaviors. Although iHFD-E mice did not have significantly altered body composition, they developed insulin insensitivity and glucose intolerance. These results suggest that access schedules determine the impact of HFD on EtOH consumption and resultant metabolic dysfunction.

animal behavior and cognition↗