DISRUPTION OF CEREBELLAR MATURATION BY AN ANTIMITOTIC AGENT IMPAIRS THE ONTOGENY OF EYEBLINK CONDITIONING IN RATS

This study represents an attempt to establish a relationship between m aturation of the cerebellum and the ontogeny of eyeblink conditioning in the rat. Experiments 1 and 2 examined the effects of disrupting cer ebellar maturation by neonatal exposure to the antimitotic agent methy lazoxymethanol (MAM) on the ontogeny of eyeblink conditioning in infan t rats, Experiment I demonstrated that neonatal exposure to MAM on Pos tnatal Day 4 (PND4) and 7 severely disrupted cerebellar maturation, Th is effect appeared to be specific in that there was no overt dysmorpho logy in other brain regions, MAM treatment also severely disrupted ass ociative 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 beh avior, In Experiment 2, MAM was given on PND4 and 7 and pups were test ed behaviorally on PND17-18, 20-21, or 31-32, Cerebellar hypoplasia wa s most dramatic shortly after exposure, The cerebellar cortex continue d to mature after exposure to MAM, but development of morphological en dpoints examined here were static from PND19 to 33. Eyeblink condition ing 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 im portant for the ontogeny of eyeblink conditioning.