Department of Neural and Behavioral Sciences, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 Jan;300(1):G21-32. doi: 10.1152/ajpgi.00363.2010. Epub 2010 Oct 14.
The dorsal motor nucleus of the vagus (DMV) is pivotal in the regulation of upper gastrointestinal functions, including motility and both gastric and pancreatic secretion. DMV neurons receive robust GABA- and glutamatergic inputs. Microinjection of the GABA(A) antagonist bicuculline (BIC) into the DMV increases pancreatic secretion and gastric motility, whereas the glutamatergic antagonist kynurenic acid (KYN) is ineffective unless preceded by microinjection of BIC. We used whole cell patch-clamp recordings with the aim of unveiling the brain stem neurocircuitry that uses tonic GABA- and glutamatergic synapses to control the activity of DMV neurons in a brain stem slice preparation. Perfusion with BIC altered the firing frequency of 71% of DMV neurons, increasing firing frequency in 80% of the responsive neurons and decreasing firing frequency in 20%. Addition of KYN to the perfusate either decreased (52%) or increased (25%) the firing frequency of BIC-sensitive neurons. When KYN was applied first, the firing rate was decreased in 43% and increased in 21% of the neurons; further perfusion with BIC had no additional effect in the majority of neurons. Our results indicate that there are several permutations in the arrangements of GABA- and glutamatergic inputs controlling the activity of DMV neurons. Our data support the concept of brain stem neuronal circuitry that may be wired in a finely tuned organ- or function-specific manner that permits precise and discrete modulation of the vagal motor output to the gastrointestinal tract.
迷走神经背核(DMV)在调节上消化道功能方面起着关键作用,包括运动和胃和胰腺分泌。DMV 神经元接受强大的 GABA 和谷氨酸能输入。将 GABA(A)拮抗剂荷包牡丹碱 (BIC) 微注射到 DMV 中会增加胰腺分泌和胃动力,而谷氨酸能拮抗剂烟酰胺 (KYN) 在微注射 BIC 之前是无效的。我们使用全细胞膜片钳记录,旨在揭示使用紧张性 GABA 和谷氨酸能突触来控制脑干切片制备中 DMV 神经元活动的脑干神经回路。用 BIC 灌注改变了 71%的 DMV 神经元的放电频率,使 80%的反应性神经元的放电频率增加,使 20%的神经元的放电频率降低。在灌流液中加入 KYN 要么降低(52%)要么增加(25%)BIC 敏感神经元的放电频率。当首先应用 KYN 时,43%的神经元的放电率降低,21%的神经元的放电率增加;进一步用 BIC 灌注对大多数神经元没有额外的影响。我们的结果表明,控制 DMV 神经元活动的 GABA 和谷氨酸能输入的排列有几种组合。我们的数据支持脑干神经元回路的概念,该回路可能以精细调节的器官或功能特异性方式布线,从而允许对胃肠道的迷走运动输出进行精确和离散的调节。