Green John T
Department of Psychology, University of Vermont, Burlington 05405-0134, USA.
Cerebellum. 2004;3(3):178-87. doi: 10.1080/14734220410017338.
In rats, developmental ethanol exposure has been used to model the central nervous system deficits associated with human fetal alcohol syndrome. Binge-like ethanol exposure of neonatal rats depletes cells in the cerebellum, including Purkinje cells, granule cells, and deep nuclear cells, and produces deficits in simple tests of motor coordination. However, the extent to which anatomical damage is related to behavioral deficits has been difficult to estimate. Eyeblink classical conditioning is known to engage a discrete brain stem-cerebellar circuit, making it an ideal test of cerebellar functional integrity after developmental ethanol exposure. Eyeblink conditioning is a simple form of motor learning in which a neutral stimulus (such as a tone) comes to elicit an eyeblink when repeatedly paired with a stimulus that evokes an eyeblink prior to training (such as mild periorbital stimulation). In eyeblink conditioning, one of the deep cerebellar nuclei, the interpositus nucleus, as well as specific Purkinje cell populations, are sites of convergence for tone conditioned stimulus and somatosensory unconditioned stimulus information, and, together with brain stem nuclei, provide the necessary and sufficient substrate for the learned response. A series of studies have shown that eyeblink conditioning is impaired in both weanling and adult rats given binge-like exposure to ethanol as neonates. In addition, interpositus nucleus neurons from ethanol-exposed rats showed impaired activation during eyeblink conditioning. These deficits are accompanied by a permanent reduction In the deep cerebellar nuclear cell population. Because particular cerebellar cell populations are utilized in well-defined ways during eyeblink conditioning, conclusions regarding the underlying neural substrates of behavioral change after developmental ethanol exposure are greatly strengthened.
在大鼠中，发育过程中接触乙醇已被用于模拟与人类胎儿酒精综合征相关的中枢神经系统缺陷。对新生大鼠进行类似暴饮的乙醇暴露会使小脑细胞减少，包括浦肯野细胞、颗粒细胞和深部核细胞，并在简单的运动协调测试中产生缺陷。然而，解剖学损伤与行为缺陷之间的关联程度一直难以估计。眨眼经典条件反射已知涉及一个离散的脑干 - 小脑回路，这使其成为发育过程中乙醇暴露后小脑功能完整性的理想测试。眨眼条件反射是一种简单的运动学习形式，其中一个中性刺激（如音调）在与训练前能诱发眨眼的刺激（如轻度眶周刺激）反复配对后，会开始诱发眨眼。在眨眼条件反射中，小脑深部核团之一的间位核以及特定的浦肯野细胞群是音调条件刺激和体感非条件刺激信息汇聚的部位，并且与脑干核团一起，为习得反应提供了必要且充分的基础。一系列研究表明，新生期接受类似暴饮乙醇暴露的断奶大鼠和成年大鼠的眨眼条件反射均受损。此外，来自乙醇暴露大鼠的间位核神经元在眨眼条件反射期间显示出激活受损。这些缺陷伴随着小脑深部核细胞群的永久性减少。由于在眨眼条件反射过程中特定的小脑细胞群以明确的方式被利用，关于发育过程中乙醇暴露后行为变化的潜在神经基础的结论得到了极大的加强。
