High Fat Diet‐Induced Neuroplasticity in Cardiac‐Projecting Dorsal Motor Nucleus of the Vagus (DMV) Motoreurons

• DOI: 10.1096/fasebj.2022.36.s1.r3711
• Publication Date: 2022-05-03T08:40:44Z
• Authors: Liliana Espinoza; Carie R. Boychuk
• Keywords: Dorsal motor nucleus; Tonic (physiology)

The DMV is critical in the maintenance of gastrointestinal (GI) function and metabolism through its axonal projections to subdiaphragmatic organs. However, there a subpopulation choline acetyltransferase (ChAT) positive neurons that send cardiac tissue. Given their anatomical apposition nuclei regulating GI metabolic function, it likely vagal motorneurons (CVNs) are sensitive nutrient signals such as high fat diet (HFD). We hypothesized HFD exposure for 15 days modulates electrophysiological properties CVNs, thus restraining ability discharge. Mice underwent retrograde tracing identify were challenged with (60%) or control chow, used whole-cell patch-clamp electrophysiology. When comparing CVNs from HFD-fed animals under current clamp conditions, no significant differences firing frequency, resting membrane potential, input resistance found normal conditions. mice exhibited increase evoked action potentials (APs) following blockade inhibitory, gamma-aminobutyric acid type-A receptor (GABAA R) neurotransmission bicuculline methiodide (BIC; 30 µM; n=10; 5.02±1.23 APs) compared previous artificial cerebrospinal fluid conditions (aCSF; 4.2±0.92 APs; p<0.0001). controls demonstrated between BIC aCSF (n=10; p=0.1194). Taken together, increased CVN sensitivity antagonism GABAA Rs. Additional studies using voltage configuration assessed two signaling modalities GABA: phasic/synaptic tonic/extrasynaptic. Spontaneous phasic inhibitory post-synaptic currents not different amplitude, decay time. had tonic R after application (n=9; 1.35±0.19 pA/pF) (n=7; 0.8±0.11 pA/pF; p=0.0361). δ subunit-containing Rs (δ)Rs) theorized mediate GABAergic current, follow-up experiments specific (δ)R agonist, THIP (3 µM) followed by BIC. Although BIC-sensitive increases remained mice, induced either group application, suggesting all (δ)Rs actively contributing these Since antagonists exist (δ)Rs, we developed transgenic mouse line where subunit knocked out ChAT (i.e. ChAT/GABAA (δ)R-null mice) determine whether changes could be prevented. Preliminary findings indicate ablation was enough prevent HFD-induced APs (n=6; 4.58±1.05 (4.5±0.98 p=0.9559). These data suggest express more responsible generation long-term inhibition exposure, discharge potentially reducing capacity cardiovascular regulation. early electrophysiology impact only but lead other comorbidities, including obesity, since exercise linked regulation DMV. Further warranted mechanistic underpinnings neuroplasticity.