Herman Melissa A, Cruz Maureen T, Sahibzada Niaz, Verbalis Joseph, Gillis Richard A
Interdisciplinary Program in Neuroscience, Georgetown Univ. Medical Center, 3900 Reservoir Rd., NW, Washington, DC 20057, USA.
Am J Physiol Gastrointest Liver Physiol. 2009 Jan;296(1):G101-11. doi: 10.1152/ajpgi.90504.2008. Epub 2008 Nov 13.
It has been proposed that there is an "apparent monosynaptic" connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes (6). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release l-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABA(A) receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (-1.6 +/- 0.2 mmHg, P < 0.05, n = 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABA(A) receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or N(G)-nitro-l-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABA(A) receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABA(A) receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit.
有人提出，胃迷走神经传入神经末梢与孤束核（NTS）中的抑制性投射神经元之间存在“明显的单突触”连接，并且来自迷走神经背运动核（DMV）的两条传出平行通路会影响与这些反射相关的外周器官（6）。我们研究的目的是验证这些观点与胃动力基础控制相关的有效性。为了测试已知释放L-谷氨酸的迷走神经传入末梢直接影响二级投射神经元的直接连接的有效性，我们评估了孤束核内侧亚核（mNTS）区域中GABA(A)受体阻断对胃动力的影响。向mNTS微量注射甲磺酸荷包牡丹碱可使胃动力显著降低（-1.6±0.2 mmHg，P<0.05，n = 23），而颈迷走神经切断术以及向mNTS微量注射犬尿氨酸预处理可防止这种情况。犬尿氨酸本身对胃动力没有影响。然而，在mNTS中进行GABA(A)受体阻断后，犬尿氨酸可使胃动力显著增加。为了测试两条平行的DMV传出通路的作用，我们评估了静脉注射甲基溴化阿托品或N(G)-硝基-L-精氨酸甲酯对基础动力以及mNTS中GABA(A)受体阻断诱导的胃动力降低的影响。只有甲基溴化阿托品改变了基础动力并阻止了GABA(A)受体阻断对胃动力的影响。我们的数据表明，在迷走神经传入神经末梢与NTS中的抑制性投射神经元之间存在NTS内的GABA能信号传导，并且胆碱能-胆碱能兴奋性通路构成了迷走-迷走回路中功能相关的传出臂。
