Freeman J H, Barone S, Stanton M E
Department of Psychology, University of North Carolina at Chapel Hill 27599, USA.
J Neurosci. 1995 Nov;15(11):7301-14. doi: 10.1523/JNEUROSCI.15-11-07301.1995.
This study represents an attempt to establish a relationship between maturation of the cerebellum and the ontogeny of eyeblink conditioning in the rat. Experiments 1 and 2 examined the effects of disrupting cerebellar maturation by neonatal exposure to the antimitotic agent methylazoxymethanol (MAM) on the ontogeny of eyeblink conditioning in infant rats. Experiment 1 demonstrated that neonatal exposure to MAM on Postnatal Day 4 (PND4) and 7 severely disrupted cerebellar maturation. This effect appeared to be specific in that there was no overt dysmorphology in other brain regions. MAM treatment also severely disrupted associative eyeblink conditioning in rats given training on PND24 and 25. However, exposure to MAM had no effect on the unconditioned response, T-maze delayed alternation, or conditioned suppression of ongoing behavior. In Experiment 2, MAM was given on PND4 and 7 and pups were tested behaviorally on PND17-18, 20-21, or 31-32. Cerebellar hypoplasia was most dramatic shortly after exposure. The cerebellar cortex continued to mature after exposure to MAM, but development of morphological endpoints examined here were static from PND19 to 33. Eyeblink conditioning was impaired at all ages, indicating that there was no functional recovery following neonatal exposure to MAM over the age range tested. These experiments suggest that normal cerebellar maturation may be important for the ontogeny of eyeblink conditioning.
本研究旨在尝试建立大鼠小脑成熟与眨眼条件反射个体发育之间的关系。实验1和实验2研究了新生大鼠在出生后第4天（PND4）和第7天暴露于抗有丝分裂剂甲基氧化偶氮甲醇（MAM）对其小脑成熟的干扰，以及对幼鼠眨眼条件反射个体发育的影响。实验1表明，在PND4和PND7新生大鼠暴露于MAM会严重干扰小脑成熟。这种影响似乎具有特异性，因为其他脑区没有明显的畸形。MAM处理还严重干扰了在PND24和PND25接受训练的大鼠的联合眨眼条件反射。然而，暴露于MAM对非条件反应、T迷宫延迟交替或正在进行行为的条件性抑制没有影响。在实验2中，在PND4和PND7给予MAM，并在PND17 - 18、20 - 21或31 - 32对幼崽进行行为测试。暴露后不久小脑发育不全最为明显。暴露于MAM后小脑皮质继续成熟，但在此处检查的形态学终点从PND19到33保持稳定。所有年龄段的眨眼条件反射均受损，表明在测试的年龄范围内，新生大鼠暴露于MAM后没有功能恢复。这些实验表明，正常的小脑成熟可能对眨眼条件反射的个体发育很重要。
