PDF(Pubmed)
Abstract：
UNASSIGNED: Local GABAergic signaling in the dorsal vagal complex (DVC) is essential to control gastric function. While the inhibitory GABAA receptor action on motility in the DVC is well-documented, the role of the GABAB receptor on gastric function is less well-established. Microinjection of baclofen, a selective GABAB receptor agonist, in the dorsal motor nucleus of the vagus (DMV) increases gastric tone and motility, while the effect on motility in the nucleus tractus solitarius (NTS) needs to be investigated. Previous in vitro studies showed that GABAB receptors exert a local inhibitory effect in unidentified NTS neurons. Since the NTS and DMV nuclei have differential control of gastric motility, we compared GABAB receptor activation in the NTS to that reported in the DMV. We microinjected baclofen unilaterally in the NTS while monitoring intragastric pressure and compared its action to optogenetic activation of somatostatin (SST) neurons in transgenic sst-Cre::channelrhodopsin-2 (ChR2) mice. We also performed patch-clamp recordings from SST and DMV neurons in brainstem slices from these mice.
UNASSIGNED: In vivo drug injections and optogenetic stimulation were performed in fasted urethane/α-chloralose anesthetized male mice. Gastric tone and motility were monitored by an intragastric balloon inserted in the antrum and inflated with warm water to provide a baseline intragastric pressure (IGP). Coronal brainstem slices were obtained from the sst-Cre::ChR2 mice for interrogation with optogenetics and pharmacology using electrophysiology.
UNASSIGNED: The unilateral microinjection of baclofen into the NTS caused a robust increase in gastric tone and motility that was not affected by ipsilateral vagotomy. Optogenetic activation of SST neurons that followed baclofen effectively suppresses the gastric motility in vivo. In brain slices, baclofen suppressed spontaneous and light-activated inhibitory postsynaptic currents in SST and gastrointestinal-projection DMV neurons and produced outward currents.
UNASSIGNED: Our results show that GABAB receptors in the NTS strongly increase gastric tone and motility. Optogenetic stimulation in vivo and in vitro suggests that these receptors activated by baclofen suppress the glutamatergic sensory vagal afferents in the NTS and also inhibit the interneurons and the inhibitory neurons that project to the DMV, which, in turn, increase motility via a cholinergic excitatory pathway to the stomach.
UNASSIGNED: In vivo drug injections and optogenetic stimulation were performed in fasted urethane/α-chloralose anesthetized male mice. Gastric tone and motility were monitored by an intragastric balloon inserted in the antrum and inflated with warm water to provide a baseline intragastric pressure (IGP). Coronal brainstem slices were obtained from the sst-Cre::ChR2 mice for interrogation with optogenetics and pharmacology using electrophysiology.
UNASSIGNED: The unilateral microinjection of baclofen into the NTS caused a robust increase in gastric tone and motility that was not affected by ipsilateral vagotomy. Optogenetic activation of SST neurons that followed baclofen effectively suppresses the gastric motility in vivo. In brain slices, baclofen suppressed spontaneous and light-activated inhibitory postsynaptic currents in SST and gastrointestinal-projection DMV neurons and produced outward currents.
UNASSIGNED: Our results show that GABAB receptors in the NTS strongly increase gastric tone and motility. Optogenetic stimulation in vivo and in vitro suggests that these receptors activated by baclofen suppress the glutamatergic sensory vagal afferents in the NTS and also inhibit the interneurons and the inhibitory neurons that project to the DMV, which, in turn, increase motility via a cholinergic excitatory pathway to the stomach.
摘要：
■背侧迷走神经复合体（DVC）中的局部GABA能信号传导对于控制胃功能至关重要。虽然DVC中抑制性GABAA受体对运动性的作用是有据可查的，GABAB受体对胃功能的作用尚不明确.微量注射巴氯芬,一种选择性GABAB受体激动剂，在迷走神经的背运动核（DMV）增加胃张力和运动，而对孤束核（NTS）运动的影响需要研究。先前的体外研究表明GABAB受体在未鉴定的NTS神经元中发挥局部抑制作用。由于NTS和DMV核对胃运动有不同的控制，我们将NTS中的GABAB受体激活与DMV中报道的比较。我们在NTS中单侧微量注射巴氯芬，同时监测胃内压力，并将其作用与转基因sst-Cre::channel视紫红质2（ChR2）小鼠中生长抑素（SST）神经元的光遗传学激活进行了比较。我们还从这些小鼠的脑干切片中的SST和DMV神经元进行膜片钳记录。
在禁食的尿烷/α-氯醛糖麻醉的雄性小鼠中进行体内药物注射和光遗传学刺激。通过插入胃窦并用温水充气的胃内气球监测胃的张力和运动，以提供基线胃内压力（IGP）。从sst-Cre::ChR2小鼠获得冠状脑干切片，用于使用电生理学进行光遗传学和药理学询问。
■向NTS中单侧微量注射巴氯芬引起胃张力和运动能力的强劲增加，而同侧迷走神经切断术不受影响。跟随巴氯芬的SST神经元的光遗传学激活有效地抑制了体内胃运动。在大脑切片中，巴氯芬抑制SST和胃肠道投射DMV神经元中自发和光活化的抑制性突触后电流，并产生外向电流。
■我们的结果表明，NTS中的GABAB受体强烈增加了胃的张力和运动。体内和体外的光遗传学刺激表明，巴氯芬激活的这些受体抑制了NTS中的谷氨酸能感觉迷走神经传入，并且还抑制了投射到DMV的中间神经元和抑制性神经元，which,反过来,通过胆碱能兴奋途径增加运动到胃。
在禁食的尿烷/α-氯醛糖麻醉的雄性小鼠中进行体内药物注射和光遗传学刺激。通过插入胃窦并用温水充气的胃内气球监测胃的张力和运动，以提供基线胃内压力（IGP）。从sst-Cre::ChR2小鼠获得冠状脑干切片，用于使用电生理学进行光遗传学和药理学询问。
■向NTS中单侧微量注射巴氯芬引起胃张力和运动能力的强劲增加，而同侧迷走神经切断术不受影响。跟随巴氯芬的SST神经元的光遗传学激活有效地抑制了体内胃运动。在大脑切片中，巴氯芬抑制SST和胃肠道投射DMV神经元中自发和光活化的抑制性突触后电流，并产生外向电流。
■我们的结果表明，NTS中的GABAB受体强烈增加了胃的张力和运动。体内和体外的光遗传学刺激表明，巴氯芬激活的这些受体抑制了NTS中的谷氨酸能感觉迷走神经传入，并且还抑制了投射到DMV的中间神经元和抑制性神经元，which,反过来,通过胆碱能兴奋途径增加运动到胃。
