Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and high‐fat diet

2021 ◽  
Author(s):  
Lukasz Chrobok ◽  
Jasmin D Klich ◽  
Jagoda S Jeczmien‐Lazur ◽  
Kamil Pradel ◽  
Katarzyna Palus‐Chramiec ◽  
...  
2021 ◽  
Author(s):  
Lukasz Chrobok ◽  
Jasmin D Klich ◽  
Jagoda S Jeczmien-Lazur ◽  
Kamil Pradel ◽  
Katarzyna Palus-Chramiec ◽  
...  

ABSTRACTThe suprachiasmatic nuclei (SCN) of the hypothalamus functions as the brain’s primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra-SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex – the dorsal motor nucleus of the vagus (DMV), also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons largely responsible for the regulation of gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi-channel electrophysiology and patch clamp recordings to gain insight into possible daily variation in these DMV cells and how this is influenced by diet. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day which was paralleled with an enhanced synaptic input to these neurons. A high-fat diet typically damps circadian rhythms, but we found that short-term exposure to a high-fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting their responsiveness to metabolic neuromodulators. In summary, we show for the first time that neural activity at a source of vagal efferents varies with time of day and that this temporal variation is modulated by diet. These findings have clear implications for our understanding of the daily control of parasympathetic outflow.


2019 ◽  
Vol 317 (1) ◽  
pp. G40-G50 ◽  
Author(s):  
Courtney Clyburn ◽  
Caitlin A. Howe ◽  
Amy C. Arnold ◽  
Charles H. Lang ◽  
R. Alberto Travagli ◽  
...  

Perinatal high-fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to postnatal day 42 (P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABAA α subunits, whereas mRNA and protein expression were measured via qPCR and Western blotting, respectively. pHFD decreased basal antrum and corpus motility, whereas brainstem microinjection of L838,417 (positive allosteric modulator of α2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA α1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA α2/3 receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA α2/3 subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility. NEW & NOTEWORTHY Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABAA receptors expressing slower α2/3-subunits, whereas mature GABAA receptor express faster α1-subunits. After perinatal high-fat diet exposure, this developmental regulation of dorsal motor nucleus of the vagus (DMV) neurons is disrupted, increasing their tonic GABAergic inhibition, decreasing efferent output, and potentially decreasing gastric motility.


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