[대학원 생명과학과 세미나 안내]
연사 : Mary Kay Lobo 교수 (University of Maryland School of Medicine)
연제 : Molecular and neuronal subtype mechanisms of psychostimulant action
일시 : 2016년 9월 27일 (화) 오후 5시
장소 : 하나과학관 A동 102호
초청교수 : 백자현 교수
Abstract
The complex cellular heterogeneity of the striatum has been a major challenge in understanding how specific striatal neuron subtypes mediate psychostimulant-induced behaviors. To provide insight into this we are examining the two ventral striatal (nucleus accumbens- NAc) projection medium spiny neurons (MSNs), those enriched in dopamine receptor 1 vs. 2 (D1 vs. D2), in psychostimulant action. We previously demonstrated divergent roles for these two MSN subtypes in cocaine reward and locomotor behavioral outcomes. We are currently investigating the molecular mechanisms that mediate these divergent roles. We have evidence for differential induction of the early growth response 3 (Egr3) transcriptional program in each MSN subtype in response to chronic cocaine. Bidirectional expression of Egr3 in each MSN subtype results in divergent behavioral outcomes to cocaine. Further, we find that Egr3 transcriptionally regulates mitochondrial nuclear genes after chronic cocaine. These genes are increased in NAc of postmortem cocaine dependent individuals and in rodents that self-administer cocaine. The mitochondrial nuclear genes are increased in D1-MSNs and decreased in D2-MSNs after chronic cocaine. Consistent with these findings, mitochondria size and volume is distinctly altered in MSN subtypes in rodents that self-administer cocaine. Specifically, we find altered frequency of smaller mitochondria in MSN subtype dendrites, implicating altered mitochondrial fission with cocaine exposure. Further, pharmacological disruption of mitochondrial fission or MSN subtype viral mediated enhancement of mitochondrial fission alters behavioral responses to cocaine. Overall our studies provide a comprehensive understanding into the distinct molecular and energetic roles of the MSN subtypes in psychostimulant abuse.