Green John T, Johnson Timothy B, Goodlett Charles R, Steinmetz Joseph E
Department of Psychology, Indiana University, Bloomington, Indiana 47405-7007, USA.
Learn Mem. 2002 Sep-Oct;9(5):304-20. doi: 10.1101/lm.47602.
Neonatal exposure to ethanol in rats, during the period of brain development comparable to that of the human third trimester, produces significant, dose-dependent cell loss in the cerebellum and deficits in coordinated motor performance. These rats are also impaired in eyeblink conditioning as weanlings and as adults. The current study examined single-unit neural activity in the interpositus nucleus of the cerebellum in adults following neonatal binge ethanol exposure. Group Ethanol received alcohol doses of 5.25 g/kg/day on postnatal days 4-9. Group Sham Intubated underwent acute intragastric intubation on postnatal days 4-9 but did not receive any infusions. Group Unintubated Control (from separate litters) did not receive any intubations. When rats were 3-7 mo old, pairs of extracellular microelectrodes were implanted in the region of the interpositus nucleus. Beginning 1 wk later, the rats were given either 100 paired or 190 unpaired trials per day for 10 d followed by 4 d of 100 conditioned stimulus (CS)-alone trials per day. As in our previous study, conditioned response acquisition in Group Ethanol rats was impaired. In addition, by session 5 of paired acquisition, Group Sham Intubated and Group Unintubated Control showed significant increases in interpositus nucleus activity, relative to baseline, in the CS-unconditioned stimulus interval. In contrast, Group Ethanol failed to show significant changes in interpositus nucleus activity until later in training. These results indicate that the disruption in eyeblink conditioning after early exposure to ethanol is reflected in alterations in interpositus nucleus activity.
在大鼠大脑发育相当于人类孕晚期的时期,新生大鼠暴露于乙醇环境中,会导致小脑出现显著的、剂量依赖性的细胞损失以及协调运动能力缺陷。这些大鼠在断奶期和成年期的眨眼条件反射也会受损。本研究检测了新生期暴饮乙醇后成年大鼠小脑间位核的单单位神经活动。乙醇组在出生后第4至9天接受5.25克/千克/天的酒精剂量。假插管组在出生后第4至9天进行急性胃内插管,但未接受任何输注。未插管对照组(来自单独的窝)未接受任何插管。当大鼠3至7个月大时,将一对细胞外微电极植入间位核区域。从1周后开始,大鼠每天接受100次配对或190次非配对试验,持续10天,随后4天每天进行100次仅条件刺激(CS)试验。与我们之前的研究一样,乙醇组大鼠的条件反应习得受损。此外,在配对习得的第5阶段,假插管组和未插管对照组在CS - 非条件刺激间隔期间,间位核活动相对于基线有显著增加。相比之下,乙醇组直到训练后期才出现间位核活动的显著变化。这些结果表明,早期暴露于乙醇后眨眼条件反射的破坏反映在间位核活动的改变上。