Neonatal maternal separation-induced changes in glucocorticoid receptor expression in posterior interpositus interneurons but not projection neurons predict deficits in adult eyeblink conditioning

Neonatal maternal separation impairs adult eyeblink conditioning. This impairment is correlated with increases in adult glucocorticoid receptor (GR) expression in the posterior interpositus nucleus [A.A. Wilber, C. Southwood, G. Sokoloff, J.E. Steinmetz, C.L. Wellman, Neonatal maternal separation alters adult eyeblink conditioning and glucocorticoid receptor expression in the interpositus nucleus of the cerebellum, Developmental Neurobiology 67 (2007) 1751-1764], a key structure in the neural circuitry controlling eyeblink conditioning. To further localize this effect, we assessed adult eyeblink conditioning and GR expression in projection versus interneurons in the interpositus of rats that had undergone standard rearing or maternal separation (1 h/day) on postnatal days 2-14. At 3 months of age, interpositus neurons were labeled with the retrograde tracer biotinylated dextran amine (BDA). After delay eyeblink conditioning, brains were processed immunohistochemically for GR and BDA labeling of interpositus neurons. GR expression was quantified in BDA-labeled and unlabeled neurons. Neonatal maternal separation impaired adult eyeblink conditioning. Control rats had significantly less GR expression in posterior interpositus BDA-unlabeled versus BDA-labeled neurons, but this difference was absent in maternally separated rats. While neonatal separation significantly increased GR expression in BDA-labeled and unlabeled posterior interpositus neurons, only GR expression in non-BDA-labeled neurons was associated with eyeblink conditioning. Thus, neonatal maternal separation may alter interneuronal modulation of interpositus output neurons, producing deficits in adult eyeblink conditioning.