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김청섭
김청섭(Chung Sub Kim) 저자 이메일 보기
University of Texas at Austin
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조회 3933  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Enhancement of Dorsal Hippocampal Activity by Knockdown of HCN1 Channels Leads to Anxiolytic- and Antidepressant-like Behaviors

1. 논문관련 분야의 소개, 동향, 전망을 설명, 연구과정에서 생긴 에피소드

Hippocampus is the integral brain region involved in learning and memory, emotion-related learning, and stress-related psychiatric disorders such as depression and anxiety. Depression is the most life-threatening mental illness with a prevalence of about 20% worldwide. Most existing antidepressant medications work in only a small population of severely depressed patients, but have a delayed onset of action (2-6 weeks) leading to an increased risk of suicidal behavior. In a previous paper, we found that three different lines of knockout mice (TRIP8b, HCN1, and HCN2), all resulting in a reduction of the hyperpolarization activated h current, displayed antidepressant-like behaviors. The mechanisms or the brain regions involved, however, were not known. Given the lack of HCN1-specific blockers or genetic animal models that offer region-specific manipulation of HCN1 channels (the channels responsible for the h current), we developed a lentiviral shRNA system, which provides sequence-specific manipulation with spatial and temporal control and high transduction efficiency. HCN1 channels are the main isoform of HCN channels (Hyperpolarization activated, Cyclic Nucleotide gated and nonselective cation channels) and are highly expressed in the hippocampus. Hyperpolarization-activated HCN1 channels play an important role in the regulation of intrinsic membrane properties, excitability, and synaptic plasticity of neurons. We reduced HCN1 protein in the dorsal hippocampus with this powerful lentiviral shRNA system. Surprisingly, silencing of HCN1 channels in the dorsal hippocampus, which corresponds to the posterior hippocampus in humans, produced antidepressant- and anxiolytic-like effects. We further examined the mechanism underlying these altered behaviors. We found that antidepressant- and anxiolytic-like behavioral phenotypes, through silencing of HCN1 channels, was associated with an increase in dorsal hippocampal activity and antidepressant efficacy-related signaling pathways (BDNF-mTOR signaling). Not all depressed patients respond to existing antidepressant drugs and many patients with depression also experience anxiety disorders. This comorbidity of depression and anxiety causes more severe health and social problems such as higher rates of alcohol and substance abuse, suicide, and vocational impairment. Our findings are therefore critically important for the development and application of new drugs for psychiatric disorders such as depression and anxiety.

2. 연구를 진행했던 소속기관 또는 연구소에 대해 소개 부탁 드립니다.

The Center for Learning and Memory (CLM) is a basic research center comprised of neuroscientists with the shared goal of elucidating the mechanisms that govern learning and memory. Our faculty approaches the study of learning and memory from diverse disciplines, including, molecular biology, genetics, physiology, behavior, physics, and computer science. By fostering a multi-disciplinary and collaborative approach to the study of learning and memory, the CLM provides the opportunity for the exchange of ideas and expertise across disciplines and levels of analysis and creates a vibrant and interactive research and teaching environment. I am a postdoctoral research fellow in Dr. Daniel Johnston's laboratory (http://clm.utexas.edu/djlab10). We have focused our attention on neurons and synapses in the hippocampus, an area of the brain that plays an important role in learning and memory. Our research uses a variety of techniques including viral mediated gene delivery system, quantitative electrophysiological and optical imaging, behavioral testing, and computer modeling. Located within the new Norman Hackerman Building (NHB, See below)), the CLM occupies 2nd and 3rd floors of the building. (Source from Center for Learning and Memory http://clm.utexas.edu)

                                       Norman Hackerman Building (NHB)

3. 연구활동 하시면서 평소 느끼신 점 또는 자부심, 보람

When I feel that doing research and writing a research paper are getting better, I own my pride and know that it was worthwhile.

4. 이 분야로 진학하려는 후배들 또는 유학준비생들에게 도움이 되는 말씀을 해 주신다면?

Life teaches us that there exist two-kinds of people. The first type despair easily when placed in difficult situations, and eventually fold and succumb to giving up on everything. On the other hand, there is a different kind of person who constantly battles when faced with adversity. They eventually change despair into hope and move forward. Although doing research is not easy, do not give up. And also, keep in your mind - "No pain, no gain".

5. 연구활동과 관련된 앞으로의 계획이 있으시다면?

I will focus on the comorbidity of depression and epilepsy in rats.

6. 다른 하시고 싶은 이야기들....

First of all, I would like to express my sincere gratitude to my advisor, Dr. Daniel Johnston for providing me with an outstanding research environment, excellent support, and critical suggestions. Without his guidance, caring, and patience, my research would not have been possible. And also, I would like to thank lab members for their friendship. Whenever I had good or bad things in the lab, they always cheered me up. Finally, my truly love and gratitude goes to my family, my lovely wife - Hyo Sook, and my adorable son - David for their long distance support, prayer, and their best wishes. They made me feel as though I was not alone. Thanks to God!

 등록일 2012-08-16
Category: Neuroscience
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