Hengen Keith B, Behan Mary, Carey Hannah V, Jones Mathew V, Johnson Stephen M
School of Veterinary Medicine, University of Wisconsin, Madison, Madison, Wisconsin 53706, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Oct;297(4):R1028-36. doi: 10.1152/ajpregu.00239.2009. Epub 2009 Aug 12.
The 13-lined ground squirrel (Ictidomys tridecemlineatus), a hibernating species, is a natural model of physiological adoption to an extreme environment. During torpor, body temperature drops to 0-4 degrees C, and the cortex is electrically silent, yet the brain stem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain during torpor are not known. To test whether altered GABAergic function is involved in regional and seasonal differences in neuronal activity, cortical and medullary slices from summer-active (SA) and interbout aroused (IBA) squirrels were placed in a standard in vitro recording chamber. Silicon multichannel electrodes were placed in cortex, ventral respiratory column (VRC), and nucleus tractus solitarius (NTS) to record spontaneous neuronal activity. In slices from IBA squirrels, bath-applied pentobarbital sodium (300 microM) nearly abolished cortical neuronal activity, but VRC and NTS neuronal activity was unaltered. In contrast, pentobarbital sodium (300 microM) nearly abolished all spontaneous cortical, VRC, and NTS neuronal activity in slices from SA squirrels. Muscimol (20 microM; GABA(A) receptor agonist) abolished all neuronal activity in cortical and medullary slices from both IBA and SA squirrels, thereby demonstrating the presence of functional GABA(A) receptors. Pretreatment of cortical slices from IBA squirrels with bicuculline (100 microM; GABA(A) receptor antagonist) blocked pentobarbital-dependent inhibition of spontaneous neuronal activity. We hypothesize that GABA(A) receptors undergo a seasonal modification in subunit composition, such that cardiorespiratory neurons are uniquely unaffected by surges of an endogenous positive allosteric modulator.
十三条纹地松鼠（Ictidomys tridecemlineatus）是一种冬眠物种，是生理上适应极端环境的天然模型。在蛰伏期间，体温降至0-4摄氏度，皮层电活动静止，但脑干继续调节心肺功能。蛰伏期间大脑中选择性抑制的潜在机制尚不清楚。为了测试GABA能功能的改变是否与神经元活动的区域和季节性差异有关，将来自夏季活跃（SA）和间歇性觉醒（IBA）松鼠的皮层和延髓切片置于标准的体外记录室中。将硅多通道电极置于皮层、腹侧呼吸柱（VRC）和孤束核（NTS）中，以记录自发神经元活动。在IBA松鼠的切片中，浴加戊巴比妥钠（300微摩尔）几乎消除了皮层神经元活动，但VRC和NTS神经元活动未改变。相比之下，戊巴比妥钠（300微摩尔）几乎消除了SA松鼠切片中所有自发的皮层、VRC和NTS神经元活动。蝇蕈醇（20微摩尔；GABA(A)受体激动剂）消除了IBA和SA松鼠皮层和延髓切片中的所有神经元活动，从而证明存在功能性GABA(A)受体。用荷包牡丹碱（100微摩尔；GABA(A)受体拮抗剂）预处理IBA松鼠的皮层切片，可阻断戊巴比妥对自发神经元活动的依赖性抑制。我们假设GABA(A)受体在亚基组成上经历季节性修饰，使得心肺神经元对内源性正变构调节剂的激增具有独特的抗性。
