Direction 1: Developmental alcohol exposure
Ongoing project: Synaptic adaptations induced by prenatal alcohol exposure. Prenatal alcohol exposure (PAE) is a common risk factor that predisposes subjects to an array of mental disorders, particularly drug addiction. These behavioral consequences of PAE cause substantial morbidity, but available treatments are limited. One reason is the lack of sufficient understanding about the neuroadaptations induced by PAE, and how these changes contribute to PAE-induced mental disorders. This project is to explore the effects of PAE on the maturation of excitatory synapse after birth, which may contribute to the high risk of addiction in pups with PAE history
Direction 2: drug addiction
Ongoing project: Neurosubstrates mediating long-term persistence of cocaine/opiate craving. This project focuses on the neuroplasticity in long-term persistence of drug-seeking even after a prolonged withdrawal from previous drug-taking. Combining the drug self-administration model in rodents with whole-cell patch clamp recordings and in vivo / in vitro optogenetics, the neuroadaptations of striatal medium-sized spiny neurons in specific neural circuits at both cellular and synaptic levels are investigated.
Direction 3: Neurodegenerative Diseases
Ongoing project: Synpatic changes in NAc of Neurodegenerative Diseases. Ca2+permeable(CP)-AMPARs in the nucleus accumbens (NAc) are hypothesized as the potential substrate in mediating the synaptic loss and the low motivation (apathy) phenotype in subjects with high risk of Alzheimer's disease (AD) and a history of PAE. In this project, we will first evaluate, and then modify, synaptic CP-AMPARs in excitatory synaptic projections in NAc of F344 wild type vs. transgenic AD rats; and furthermore, motivation levels of rats at the adolescent, early adulthood and middle-aged stages will be tested. Our aim is to not only fill the knowledge gap in our understanding of neural mechanisms of apathy associated with AD and PAE, but also uncover novel neural targets to treat affected patients in the clinic.