Fuchs J L, Salazar E
Department of Biological Sciences, University of North Texas, Denton 76203, USA.
J Comp Neurol. 1998 Jun 1;395(2):209-16.
Both sensory deprivation and blockade of gamma-aminobutyric acid A (GABA(A)) receptors result in signs of cortical disinhibition. To investigate whether down-regulation of GABA(A) receptors could underlie effects of sensory deprivation, [3H]muscimol binding was assessed in rat whisker barrels after chronic whisker trimming. Vibrissae in row C or rows A,B,D, and E were trimmed during certain developmental periods. When whiskers were trimmed for the first 6 postnatal weeks, [3H]muscimol binding was 8.3% lower in deprived barrel rows than in adjacent nondeprived rows (P < 0.001). The effect may be somewhat selective for GABA(A) receptors because there was no evident change in N-methyl-D-aspartate (NMDA) receptors as indicated by [3H]MK-801 binding. Ten weeks after whiskers were allowed to regrow, the decrease in [3H]muscimol binding was partly reversed (P < 0.002), leaving a 3.3% decrease (P < 0.001). These declines in GABA(A) receptors could contribute to persisting electrophysiological signs of reduced inhibition in similarly deprived barrel neurons (Simons and Land [1987] Nature 326:694-697). A 6-week deprivation beginning in adulthood resulted in a 7.7% decrease (P < 0.001), indicating that the effect is not restricted to an early critical period. In rats trimmed for the first 10 postnatal days, [3H]muscimol binding declined 2.3% (P < 0.05), which is a small change compared with the magnitude of the developmental peak; thus, normal whisker input apparently is not required for the developmental increase in GABA(A) receptors. The present study suggests that sensory input can regulate cortical GABA(A) receptors in adulthood and during ontogeny. Down-regulation of cortical GABA(A) receptors may be a compensatory mechanism that serves to disinhibit the reduced sensory input.
感觉剥夺和γ-氨基丁酸A（GABA(A)）受体阻断均可导致皮质去抑制的体征。为研究GABA(A)受体下调是否为感觉剥夺效应的基础，在大鼠胡须桶状皮质中对慢性修剪胡须后的[3H]蝇蕈醇结合进行了评估。在特定发育时期修剪C排或A、B、D和E排的触须。当在出生后前6周修剪胡须时，剥夺侧桶状皮质排中的[3H]蝇蕈醇结合比相邻未剥夺侧低8.3%（P<0.001）。该效应可能对GABA(A)受体有一定选择性，因为[3H]MK-801结合显示N-甲基-D-天冬氨酸（NMDA）受体无明显变化。胡须重新生长10周后，[3H]蝇蕈醇结合的减少部分逆转（P<0.002），仍有3.3%的减少（P<0.001）。GABA(A)受体的这些减少可能导致类似剥夺侧桶状神经元中持续存在的抑制减弱的电生理体征（西蒙斯和兰德[1987]《自然》326:694 - 697）。成年期开始的6周剥夺导致减少7.7%（P<0.001），表明该效应不限于早期关键期。在出生后前10天修剪胡须的大鼠中，[3H]蝇蕈醇结合下降2.3%（P<0.05），与发育高峰的幅度相比变化较小；因此，正常的胡须输入显然不是GABA(A)受体发育性增加所必需的。本研究表明，感觉输入在成年期和个体发育过程中均可调节皮质GABA(A)受体。皮质GABA(A)受体的下调可能是一种补偿机制，用于解除对减少的感觉输入的抑制。
