题目：Neuronal ensembles in addiction

报告人：Bruce Thomas Hope, Ph.D.(Senior Investigator/PI of Neuronal Ensembles in Addiction Unit )

时间：2016年06月14日 星期二 13:00-15:00

地点： 北大王克桢楼11层1113会议室

Learned associations between drugs and environment play an important role in addiction and are thought to be encoded within specific patterns of sparsely distributed neurons called neuronal ensembles. This hypothesis is supported by correlational data from in vivo electrophysiology and cellular imaging studies in relapse models in rodents. In particular, cellular imaging with the immediate early gene c-fos and its protein product Fos has been used to identify sparsely distributed neurons that were strongly activated during conditioned drug behaviors such as drug self-administration and context- and cue-induced reinstatement of drug seeking. We have used Fos and the c-fos promoter to demonstrate causal roles for Fos-expressing neuronal ensembles in prefrontal cortex and nucleus accumbens in conditioned drug behaviors. I will be describing work using our Daun02 inactivation procedure to ablate specific neuronal ensembles and selective disruption of their associated memories. We have used fluorescence-activated cell sorting (FACS) of Fos-expressing neurons to identify unique molecular alterations that are induced only within behaviorally activated neuronal ensembles and not in the surrounding less activated neurons. We have used transgenic Fos-GFP rats and mice to demonstrate that unique electrophysiological alterations are induced only in behaviorally activated neurons and not in the surrounding less activated neurons. In general, we observe alterations only in the 1% of neurons within neuronal ensembles that were strongly activated and shown to mediate conditioned drug behaviors, with little or no alterations in the surrounding less activated neurons. We will also describe our recent Fos-Tet-Cre transgenic rats that induce Cre recombinase only in strongly activated neurons within a 6-hour time window following systemic injections of tetracycline. We have used these rats to demonstrate reactivation of similar ventromedial prefrontal cortex neuronal ensembles activated on two different days, along with optogenetic inhibition of these ensembles to demonstrate their roles in context-induced reinstatement of cocaine seeking. We now use these rats to assess the roles of our previously described molecular and cellular alterations in Fos-expressing neuronal ensembles.

Host:Lin Lu