Many studies have documented the relationship between adverse early experience and the development of psychiatric disorders such as depression, post-traumatic stress disorder, and schizophrenia. Neonatal maternal separation in the rat is a good model system for assessing the effects of adverse early experience, and eyeblink conditioning learning and memory is a good model system for studying the relationship between neonatal stress and adult behavior. This research will support the scientific integration of brain and behavior, to provide a foundation for understanding mental disorders, and will also define environmental risk for mental disorders. Previously, I showed that neonatal maternal separation increases adult glucocorticoid receptor expression in the interpositus nucleus of the cerebellum and impairs eyeblink conditioning. I have subsequently found that maternal separation during the first two postnatal weeks prevents a decrease in glucocorticoid receptor expression in the interpositus nucleus that occurs with normal development during the third postnatal week. The objective of the proposed research is to characterize the role of glucocorticoids in the impairment of learning I observed, and to explore alterations in neuronal morphology as a potential consequence of glucocorticoid alterations and mechanism of impaired eyeblink conditioning. In addition, perinatal corticosterone exposure influences development of several brain structures, including the cerebellum, and the effects we observed may be mediated by neonatal increases in corticosterone. Therefore, in two different experiments, I will assess a) the effect of glucocorticoid receptor blockade during maternal separation on adult eyeblink conditioning, neuronal morphology, and glucocorticoid receptor expression;and b) the effect of neonatal corticosterone administration on adult eyeblink conditioning and glucocorticoid receptor expression. If the increased glucocorticoid receptor expression in the interpositus nucleus is responsible for the adult eyeblink conditioning deficits we observed, then blocking these receptors during conditioning in adult rats that were separated neonatally should improve eyeblink conditioning. To test this hypothesis, I will assess the effects of infusion of a glucocorticoid receptor antagonist into the interpositus nucleus during eyeblink conditioning in neonatally separated rats. The findings of this research are relevant for public health. One in four U. S. citizens are affected by mental disorders every year. Understanding the mental health consequences of intentional (e.g., abuse and neglect) and unintentional (e.g., NICU) perinatal stressors is crucial to preventative treatment.
| Wilber, A A; Lin, G L; Wellman, C L (2011) Neonatal corticosterone administration impairs adult eyeblink conditioning and decreases glucocorticoid receptor expression in the cerebellar interpositus nucleus. Neuroscience 177:56-65 |
| Wilber, A A; Walker, A G; Southwood, C J et al. (2011) Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction. Neuroscience 174:115-31 |
| Wilber, Aaron A; Lin, Grant L; Wellman, Cara L (2010) Glucocorticoid receptor blockade in the posterior interpositus nucleus reverses maternal separation-induced deficits in adult eyeblink conditioning. Neurobiol Learn Mem 94:263-8 |
