Oh K S, Lee C J, Gibbs J W, Coulter D A
Department of Neurology, Medical College of Virginia, Richmond.
J Neurosci. 1995 Feb;15(2):1341-51. doi: 10.1523/JNEUROSCI.15-02-01341.1995.
GABAergic inhibition synchronizes oscillatory activity in the thalamocortical system. To understand better the role of this neurotransmitter in generation of thalamocortical rhythmicity, the postnatal development of GABAergic function mediated through activation of GABAA receptors was studied in thalamus and cortex. GABA-evoked chloride currents were recorded in dissociated rat cortical and thalamic neurons during postnatal development. Kinetic fits of GABA concentration/response relationships revealed developmental and regional alterations in the potency of GABA. Early in postnatal development (p5-p8), both thalamic and cortical neurons exhibited reduced potency of GABA (27-31 microM KD). Potency increased by p18-p25 in thalamic and cortical neurons (19-22 microM KD), to a level maintained in adult thalamic neurons. Adult cortical neurons exhibited reduced potency of GABA (40 microM KD). Benzodiazepine modulation of GABAA currents was also studied. Kinetic analyses of benzodiazepine augmentation of GABAA currents were best fitted assuming two effective sites with different affinities for clonazepam. The high-affinity site (KD of 0.05-0.27 nM) showed little variation with development in cortical neurons, contributing about 16-23% potentiation at all postnatal ages. Developing thalamic neurons (p5-p25) showed similar potency and efficacy of the high-affinity benzodiazepine site to cortical neurons. High-affinity benzodiazepine effects disappeared in adult thalamic neurons. A lower-affinity benzodiazepine site (25-50 nM KD) was greater in efficacy in cortical neurons compared to thalamic neurons at all ages, with efficacy ranging from 50% to 110% in cortex and from 20% to 60% in thalamus. Knowledge of developmental and regional alterations in GABAA receptor function may aid in understanding mechanisms involved in generation and control of normal and pathological thalamocortical rhythms.
γ-氨基丁酸（GABA）能抑制使丘脑皮质系统中的振荡活动同步。为了更好地理解这种神经递质在丘脑皮质节律产生中的作用，我们研究了通过激活GABAA受体介导的GABA能功能在丘脑和皮质中的产后发育。在产后发育过程中，记录了离体大鼠皮质和丘脑神经元中GABA诱发的氯离子电流。GABA浓度/反应关系的动力学拟合揭示了GABA效力的发育和区域变化。在产后发育早期（出生后第5 - 8天），丘脑和皮质神经元的GABA效力均降低（解离常数KD为27 - 31微摩尔）。到出生后第18 - 25天，丘脑和皮质神经元的效力增加（KD为19 - 22微摩尔），达到成年丘脑神经元维持的水平。成年皮质神经元的GABA效力降低（KD为40微摩尔）。还研究了苯二氮䓬对GABAA电流的调节作用。假设存在两个对氯硝西泮具有不同亲和力的有效位点，对苯二氮䓬增强GABAA电流的动力学分析拟合效果最佳。高亲和力位点（KD为0.05 - 0.27纳摩尔）在皮质神经元中随发育变化不大，在所有产后年龄段贡献约16 - 23%的增强作用。发育中的丘脑神经元（出生后第5 - 25天）对高亲和力苯二氮䓬位点的效力和效果与皮质神经元相似。成年丘脑神经元中高亲和力苯二氮䓬的作用消失。低亲和力苯二氮䓬位点（KD为25 - 50纳摩尔）在所有年龄段的皮质神经元中的效力均高于丘脑神经元，在皮质中的效力范围为50%至110%，在丘脑中为20%至60%。了解GABAA受体功能的发育和区域变化可能有助于理解正常和病理性丘脑皮质节律的产生和控制机制。
