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. 2019 Oct 1;317(4):G476-G483.
doi: 10.1152/ajpgi.00112.2019. Epub 2019 Aug 8.

Sex differences in GABAergic neurotransmission to rat DMV neurons

Yanyan Jiang  1 , Tanja Babic  1 , R Alberto Travagli  1
Affiliations

Sex differences in GABAergic neurotransmission to rat DMV neurons

Yanyan Jiang et al. Am J Physiol Gastrointest Liver Physiol. .

Abstract

Functional gastrointestinal disorders, including delayed gastric emptying and decreased gastric motility, are more prevalent in women, suggesting a potential role for circulating gonadal hormones, including estrogen. Gastric motility is tuned by the vagal inputs arising from the dorsal motor nucleus of the vagus (DMV), which is itself controlled by tonic GABAergic inputs. Estrogen increases GABA functions in various central nervous system areas; however, the effect of the estrus cycle in modulating GABAergic inputs onto DMV neurons, hence vagal control of gastric motility, has not been investigated. The aim of the present study was to test the hypothesis that GABAergic tone to DMV neurons, hence the vagal output to the stomach, varies according to sex and the estrus cycle. Experiments were performed on age-matched Sprague-Dawley male and virgin female rats; females were subdivided according to the high-estrogen (HE) or low-estrogen (LE) period of their cycle. Whole-cell patch-clamp recordings were made from gastric-projecting DMV neurons, and the response to perfusion with the GABAA receptor antagonist bicuculline was examined. The response of corpus and antrum tone and motility to bicuculline microinjected in the dorsal vagal complex, recorded via strain gauges sewn to the anterior gastric surface, was also assessed. Bicuculline increased the firing rate of DMV neurons, as well as gastric tone and motility, to a larger extent in HE compared with LE or male rats, suggesting a higher GABAergic tone in HE female rats. Taken together, the data support the hypothesis that GABAergic tone to DMV neurons varies according to sex and estrus cycle.NEW & NOTEWORTHY GABAergic neurotransmission to the dorsal motor nucleus of the vagus (DMV) plays a pivotal role in the modulation of gastric tone and motility. Gastric motility is reduced in women and may contribute to the higher incidence of functional gastrointestinal disorders. In the present study, we report that GABAergic tone to rat DMV neurons, hence vagal output to the stomach, varies according to sex and estrus cycle, and the GABAergic tone is increased during the high-estrogen period of the estrus cycle.

Keywords: brainstem; electrophysiology; gastric motility; vagus.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

None
Graphical abstract
Fig. 1.
Fig. 1.
Dorsal motor nucleus of the vagus (DMV) neurons from female high estrogen (HE) rats are less excitable. A: representative traces of single action potentials evoked in DMV neurons from male (black), female low estrogen (LE) (blue), and female-HE (red) groups. Neurons were clamped at −60 mV before injection of a short (16 ms) depolarizing current pulse of intensity sufficient to evoke a single action potential at its offset. Note that the amplitude of the action potential from female-HE rats displayed a larger and slower hyperpolarization (AHP). B: graphic representation of the AHP amplitude in DMV neurons from male (34 neurons from 10 rats), female-LE (17 neurons from 7 rats), and female-HE (24 neurons from 7 rats). *P < 0.05 vs. male and female-LE. C: representative traces showing the response of DMV neurons from male (black, left) and female-HE (red, right) rats following injection of 10 pA and 90 pA DC (400 ms long). D: frequency-response curves for DMV neurons from male, female-LE (blue), and female-HE (red) rats. Note the neurons from female-HE rats are less excitable and fire fewer action potentials than neurons from other groups when injected with 50–90 pA current. Holding potential = −60 mV. *P < 0.05 vs. male and female-LE. DC, direct current.
Fig. 2.
Fig. 2.
Dorsal motor nucleus of the vagus (DMV) neurons from female high estrogen (HE) rats have a larger response to bicuculline application. A: representative trace of action potentials recorded in a DMV neuron from male rats. Note that application of 0.5 μM bicuculline did not increase action potential firing rate. B: representative trace of action potentials recorded in a DMV neuron from female-HE rats. Note that application of 0.5 μM bicuculline increased action potential firing rate to a larger extent compared with male. C: summary graph representing the responsiveness in firing rate to the application of 0.5 μM and 5 μM bicuculline. Note neurons from female-HE have a larger response in firing rate. *P < 0.05 vs. male and female low estrogen (LE), #P < 0.05 vs. male.
Fig. 3.
Fig. 3.
Microinjection of bicuculline in the dorsal vagal complex (DVC) induced a larger increase in corpus tone and motility in female high estrogen (HE) rats. A: representative recordings from the corpus of a male (top, black), female low estrogen (LE) (middle, blue), and female-HE (bottom, red) showing the increase in tone and motility upon microinjection (upward arrow) of bicuculline (0.5 pmol/60 nL). Note the increase in tone and motility in female-HE rats is larger compared with male and female-LE rats. B: summary graph representing the effects of bicuculline (0.1 pmol and 0.5 pmol) microinjection in the DVC on corpus tone in male (black), female-LE (blue), and female-HE (red) rats. Note that both 0.1 and 0.5 pmol bicuculline-induced increase in corpus tone is significantly larger in female-HE rats. *P < 0.05 vs. male. C: summary graph representing the effects of bicuculline (0.1 pmol and 0.5 pmol) microinjection in the DVC on corpus motility in male (black), female-LE (blue), and female-HE (red) rats. Note that 0.5 pmol bicuculline-induced increase in corpus motility is significantly larger in female-HE rats. *P < 0.05 vs. male.
Fig. 4.
Fig. 4.
Microinjection of bicuculline in the dorsal vagal complex (DVC) induced a larger increase in antrum tone and motility in female high estrogen (HE) rats. A: representative recordings from the antrum of a male (top, black), female low estrogen (LE) (middle, blue), and female-HE (bottom, red) showing the increase in antrum tone and motility upon microinjection (upward arrow) of bicuculline (0.5 pmol/60 nL). Note the increase in tone and motility in female-HE rats is larger compared with male and female-LE rats. B: summary graph representing the effects of bicuculline (0.1 pmol and 0.5 pmol) microinjection in the DVC on antrum tone in male (black), female-LE (blue), and female-HE (red) rats. Note that both 0.1 and 0.5 pmol bicuculline-induced increase in antrum tone is significantly larger in female-HE rats. *P < 0.05 vs. male. C: summary graph representing the effects of bicuculline (0.1 pmol and 0.5 pmol) microinjection in the DVC on corpus motility in male (black), female-LE (blue), and female-HE (red) rats. Note that 0.5 pmol bicuculline-induced increase in antrum motility is significantly larger in female-HE rats. *P < 0.05 vs. male.
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References

    1. Aytuğ N, Giral A, Imeryüz N, Enç FY, Bekiroğlu N, Aktaş G, Ulusoy NB. Gender influence on jejunal migrating motor complex. Am J Physiol Gastrointest Liver Physiol 280: G255–G263, 2001. doi:10.1152/ajpgi.2001.280.2.G255. - DOI - PubMed
    1. Babic T, Browning KN, Travagli RA. Differential organization of excitatory and inhibitory synapses within the rat dorsal vagal complex. Am J Physiol Gastrointest Liver Physiol 300: G21–G32, 2011. doi:10.1152/ajpgi.00363.2010. - DOI - PMC - PubMed
    1. Bond EF, Heitkemper MM, Perigo R. Gastric emptying and gastric-intestinal transit in rats with varying ovarian hormone status. Nurs Res 45: 218–224, 1996. doi:10.1097/00006199-199607000-00005. - DOI - PubMed
    1. Browning KN, Babic T, Holmes GM, Swartz E, Travagli RA. A critical re-evaluation of the specificity of action of perivagal capsaicin. J Physiol 591: 1563–1580, 2013. doi:10.1113/jphysiol.2012.246827. - DOI - PMC - PubMed
    1. Chen TS, Doong ML, Chang FY, Lee SD, Wang PS. Effects of sex steroid hormones on gastric emptying and gastrointestinal transit in rats. Am J Physiol Gastrointest Liver Physiol 268: G171–G176, 1995. doi:10.1152/ajpgi.1995.268.1.G171. - DOI - PubMed

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