Perinatal high fat diet increases inhibition of dorsal motor nucleus of the vagus neurons regulating gastric functions

Abstract

Background: Previous studies suggest an increased inhibition of dorsal motor nucleus

High-Fat Diet During the Perinatal Period Induces Loss of Myenteric Nitrergic Neurons and Increases Enteric Glial Density, Prior to the Development of Obesity

“…Our previous studies (Bhagat et al, 2015; McMenamin et al, 2017) previous demonstrated alterations in central vagal neurocircuits in response to a PNHFD. In fact, the intrinsic membrane properties of central vagal neurons are dysfunctional following exposure to a PNHFD, even prior to the onset of obesity; dorsal motor nucleus of the vagus (DMV) neurons that innervate the stomach are less excitable, have a lower membrane input resistance, and fire fewer action potentials in response to depolarizing inputs (Bhagat et al, 2015).…”

“…In fact, the intrinsic membrane properties of central vagal neurons are dysfunctional following exposure to a PNHFD, even prior to the onset of obesity; dorsal motor nucleus of the vagus (DMV) neurons that innervate the stomach are less excitable, have a lower membrane input resistance, and fire fewer action potentials in response to depolarizing inputs (Bhagat et al, 2015). Furthermore PNHFD also induces dysregulation of the synaptic inputs these vagal efferent motoneurons receive, including an increased response to the GABA A receptor antagonist, bicuculline, suggesting an increase in tonic GABAergic synaptic input (McMenamin et al, 2017). It should be noted that, while DMV neurons are spontaneously active and display pacemaking properties, firing action potentials at approximately 1 Hz (Travagli & Gillis, 1994), their excitability is sculpted continuously by the variety of synaptic inputs they receive (Travagli et al, 1991; Davis et al, 2004; Babic et al, 2011) most notably from the adjacent nucleus of the tractus solitarius (NTS).…”

Role of astroglia in diet-induced central neuroplasticity

“…Diet can have profound effects on synaptic strength in many areas of the brainstem, including those in the dorsal vagal complex (DVC), which includes the dorsal motor nucleus of the vagus (DMV), the nucleus tractus solitarius (NTS), and the area postrema (AP) (Bhagat et al 2015;Clyburn et al 2018;Kentish et al 2012Kentish et al , 2016McMenamin et al 2018;Travagli and Anselmi 2016;Troy et al 2016). DVC neurocircuits are responsible for integrating and responding to peripheral sensory information from cardiovascular, respiratory, and gastrointestinal (GI) systems (Lu and Bieger 1998;Travagli and Anselmi 2016).…”

“…Indeed, several studies have suggests that acute neuroinflammation is protective against a wide range of insults, including hemorrhage, whereas chronic neuroinflammation induces significant damage and disruption to neurocircuit function (Astiz et al 2017;Burda and Sofroniew 2014). Chronic HFD exposure and DIO, for example, decrease vagal motoneuron excitability, alter neuronal morphology, and inhibit the CCK-induced modulation of synaptic transmission (Bhagat et al 2015;McMenamin et al 2018).…”

“…Prolonged exposure to a high-fat diet (HFD) increases food and caloric intake per meal, resulting in weight gain and increased adiposity in both humans and animal models alike (Daly et al 2011;de Lartigue et al 2011). Interestingly, prolonged HFD exposure and diet-induced obesity (DIO) are associated with not only dysregulation of autonomic and metabolic functions related to energy homeostasis (Chaar et al 2016; Kentish et al 2016;Little and Feinle-Bisset 2011;Little et al 2007;McMenamin et al 2018;Troy et al 2016), but also the disruption of higher order functions such as learning, memory, mood, reward processes, and hippocampal activity (Cano et al 2014;Hao et al 2016;Spencer et al 2017;Wu et al 2018). One common thread between DIO and its wide range of comorbid disorders is the inflammation associated with increased adiposity (Ávalos et al 2018;Belegri et al 2018;Dalvi et al 2017;Guillemot-Legris et al 2016;Spencer et al 2017).…”