Biology subjects

Boychuk, C. R.

Publications and source records attributed to Boychuk, C. R..

3 recordsLinked to original sources

bioRxiv2026

PKCδ mediates high-fat diet-induced increased tonic GABAA receptor current in cardiac vagal motor neurons in the DMV

Consumption of high fat diet (HFD) is linked to reduced cardiac vagal motor output, a main contributor to progression of cardiovascular disease. HFD for 15 days increases extrasynaptic or tonic gamma aminobutyric acid (GABA) current in cardiac projecting neurons in the dorsal motor nucleus of the vagus (CVNDMV), which contributes to dampening cardiac parasympathetic output. However, the mechanism underlying this increased inhibition is unknown. Here, we hypothesize that increased activity of protein kinase C {delta} isoform (PKC{delta}) enhances tonic GABA current in CVNDMV after HFD. Whole-cell patch-clamp recording of retrogradely labeled CVNDMV demonstrated that pan inhibition of PKC activity with GFX, and isoform specific inhibition of PKC{delta} with rottlerin normalize 15-day HFD-induced increases in tonic GABA current, suggesting that PKC{delta} mediates enhanced tonic inhibition. This effect persisted in the presence of dynasore, a clathrin-mediated endocytosis blocker, indicating that the normalization effect of PKC{delta} inhibition on tonic current in HFD is likely independent of clathrin-mediated endocytosis. Furthermore, no differences in PKC{delta} mRNA or protein expression were observed between NFD and HFD, suggesting a post-translational mechanism underpinning increased tonic GABA current after 15 days of HFD. Altogether, this study provides evidence that HFD-induces increased PKC{delta} activity, but not expression, leading to increased tonic GABAergic inhibition in CVNDMV. This increase PKC{delta} activity could explain the cardiac vagal motor output dampening in CVD and be developed into treatments targeting PKC{delta} for CVD.

neuroscience↗

bioRxiv2025

Autonomic reflex plasticity associates with time-dependent SUDEP susceptibility in a murine model with hyperactive stress circuits

Sudden unexpected death in Epilepsy (SUDEP) is the leading cause of death in patients with Epilepsy. Although SUDEP results from cardiorespiratory arrest, its underlying mechanisms are poorly understood. Considering the significant association between stress-related disorders and Epilepsy, we hypothesized that stress exaggerates autonomic reflexes critical in cardiorespiratory function and that these exaggerated reflexes increase susceptibility to SUDEP. Experiments were performed using a novel mouse model of SUDEP where hyperreactivity of central corticotropin-releasing hormone (CRH) neurons (Kcc2/Crh) predisposes mice to SUDEP in the weeks following seizure induction based on the ventral intrahippocampal kainate (vIHKA) model of chronic Epilepsy. In our study, the vIHKA model was employed in both wild-type (WT) and Kcc2/Crh mice while they were monitored with EEG and ECG using in vivo telemetry and underwent terminal autonomic reflex testing at time points when mortality peaked and plateaued. A resting tachycardia developed by one week following vIHKA injection but subsided by day 30 in both WT and Kcc2/Crh mice. During spontaneous seizures, Kcc2/Crh mice had more pronounced reflex-like ictal bradycardias compared to WT controls that notably occurred prior ([~]10 sec) to seizure termination. vIHKA injection promoted time-dependent exaggeration of autonomic reflexes, with Kcc2/Crh mice exhibiting robust autonomic disturbances compared to WT controls, including a pronounced serotonin-mediated Bezold Jarisch reflex. Taken together, our findings indicate that increased autonomic disturbance burden parallels time-dependent SUDEP susceptibility in mice with hyperreactive stress circuits.

neuroscience↗

bioRxiv2023

Dorsal Motor Vagal Neurons Can Elicit Bradycardia and Reduce Anxiety-Like Behavior

Cardiovagal neurons (CVNs) innervate cardiac ganglia through the vagus nerve to control cardiac function. Although the cardioinhibitory role of CVNs in nucleus ambiguus (CVNNA) is well established, the nature and functionality of CVNs in dorsal motor nucleus of the vagus (CVNDMV) is less clear. We therefore aimed to characterize CVNDMV anatomically, physiologically, and functionally. Optogenetically activating cholinergic DMV neurons resulted in robust bradycardia through peripheral muscarinic (parasympathetic) and nicotinic (ganglionic) acetylcholine receptors, but not beta-1-adrenergic (sympathetic) receptors. Retrograde tracing from the cardiac fat pad labeled CVNNA and CVNDMV through the vagus nerve. Using whole cell patch clamp, CVNDMV demonstrated greater hyperexcitability and spontaneous action potential firing ex vivo despite similar resting membrane potentials, compared to CVNNA. Chemogenetically activating DMV also caused significant bradycardia with a correlated reduction in anxiety-like behavior. Thus, DMV contains uniquely hyperexcitable CVNs capable of cardioinhibition and robust anxiolysis.

neuroscience↗