The Role of Adult Hippocampal Neurogenesis and Synaptic Changes in Mediating Extinction Retention Deficit in a Rodent Model of PTSD

[摘要] Post-traumatic stress disorder (PTSD) is a severe and debilitating disorder that can emerge following exposure to a traumatic event. The development of effective rehabilitation strategies requires identification of specific and modifiable targets that can ease the burden of PTSD symptomatology. Functionally, prefrontal cortex (PFC)–hippocampus (Hpc) circuitry is critical for extinction retention (ER) and contextual processing, and PTSD patients have been shown to have impairments in these functions. PTSD patients have been shown to have smaller Hpc and PFC and show lower activation in these areas during ER compared to controls. We have developed and extensively studied an animal model of PTSD - Single Prolonged Stress (SPS) – characterized by context-dependent extinction retention and fear renewal deficits. My research focused on two possible cellular mechanisms that may underlie SPS-induced extinction retention deficit within contextual processing neuro-circuitry. Specifically, I investigated a possible role of adult hippocampal neurogenesis in contributing to SPS induced extinction retention deficits in chapter 2. In chapter 3, I investigated if SPS would change gene expression of a selected number of synaptic markers within key brain regions involved in contextual processing and fear responding: mPFC, Hpc and Amyg (amygdala). I found several lines of evidence supporting a role for adult hippocampal neurogenesis in extinction retention deficits. Specifically, elimination of neurogenesis through irradiation resulted in extinction retention deficit, SPS exposure decreased the numbers of proliferating dentate gyrus cells, immature neurons and surviving dentate gyrus cells, and an intervention aimed at promoting neuronal cell survival rescued SPS-induced extinction retention deficit. I also found that expression of some synaptic markers was altered by SPS exposure. Specifically, several proteins involved in synaptic structure were decreased while several proteins associated with synaptic signaling and function were increased, suggesting possible changes in synaptic morphology accompanied by a functional compensation within these regions that could mediate extinction retention deficits.

[发布机构] University of Michigan

[效力级别] Science (General)

[关键词] The role of adult hippocampal neurogenesis and synaptic changes in mediating extinction retention deficit in a rodent model of PTSD;Science (General);Science;Neuroscience