Absence makes the heart grow fonder but doesn't do wonders for learning and memory

Given the relationship between adverse early experience and the development of psychiatric disorders, understanding the mental health consequences of perinatal stressors is crucial for preventative treatment. Neonatal maternal separation in the rat is a good model system for adverse early experience, and eyeblink conditioning is a form of associative learning whose neural basis is well characterized. We have used these model systems to study the relationship between neonatal stress and adult learning and memory. We have shown that neonatal maternal separation (1 h/day on postnatal days 2–14) impairs adult eyeblink conditioning and increases glucocorticoid receptor (GR) expression in a critical site of learning related plasticity, the interpositus nucleus of the cerebellum. Further, we assessed interpositus GR expression early in development, and demonstrated that maternal separation prevented a normally‐occurring decrease in GR expression from postnatal day 15 to 21. Finally, we examined the effect of GR blockade in the interpositus on eyeblink conditioning, and showed that infusion of a GR blocker into the interpositus before training normalized eyeblink conditioning in adult separated rats. Thus, maternal separation impairs eyeblink conditioning by altering normal developmental changes in GR expression, and the increased GR expression may mediate the adult deficit in eyeblink conditioning. Grant Funding Source : MH085415 to AW and the Indiana METACyt Initiative of Indiana University to CLW