We are interested in elucidating how neurons are interconnected and affect each other, and how synapses are modified at the cellular and molecular level. Synapses can vary in their size, strength, and the number.
These differences contribute to learning and memory, beyond the plasticity of neural networks and synapses.

First, we study synaptic plasticity by means of changes in the level of gene expression or circuit specific modulation using viral vectors and transgenic animals. Using genetically modified materials, we can reveal mechanism of spike time dependent plasticity (STDP}, dopamine and it's receptors role in synaptic plasticity or involvement of cell adhesion molecules such as Neuroligin-1. Whole-cell recording is a critical method for observing neural activity in living neurons, and this technique to observe changes of synaptic plasticity. Moreover, we apply behavior experiment using rodents, to find the physiological meaning of alteration in synaptic plasticity.

Second, neurodegenerative diseases or neuropsychiatric disorders appear apparent with failures in synaptic functions and plasticity. Therefore, we pursue the pathophysiology and specific molecular mechanisms of neuronal diseases such as Alzheimer's disease (AD}, autism, or bipolar disorder. Toward this end, we employ variety methodologies, inducing varied behavioral tests, electrophysiological studies in vivo or acute slice, time-lapse imaging of synaptic structures, and optical determination of bimolecular interaction as well as standard biochemical assays.

Third, chronic exposure to drugs of abuse (e.g. cocaine} makes longlasting addictive memory. We investigate electrophysiological, structural and behavioral changes to study long-term changes of reward circuit. Because dopamine Dl and D2 receptor show opposite direction of response in the nucleus accumbens, and they are separately expressed in specific cell type, we are eager to distinguish the functional properties of each type of neurons. BAC transgenic mice (Drdla-EGFP, Drd2-EGFP} enable us to study drug addiction in a celltype specific manner.

Finally, we also conduct systemic approach to study neuronal circuits for functional understanding of various brain areas. For this, we employ a cutting-edge method, opto-or chemo-genetics, which enables us to control the activity of distinct type or group of neurons by optical-or chemical-stimuli and Engram labeling tool, which can label the activated neuronal groups by distinct stimuli. Thus, we can accurately see the role of only optically stimulated neural population or stimuli specific responsible neuronal population in vivo. Currently we are applying these techniques on drug addiction and fear memory research.

뇌는 독보적으로 우리의 몸에서 가장 많고 다양한 gene이 발현되며, 복잡한 구조를 가지고 있는 부위이다. 뇌가 복잡할 수밖에 없는 이유는 우리 몸의 대부분 행동을 control하며, 감각기관으로부터 들어오는 여러 정보를 종합적으로 처리하여 적절한 판단을 내리기 때문이다. 또한, 뇌는 현재의 정보뿐만 아니라, 과거에 처리되었던 정보와 행위, 그로 인한 결과까지 저장해두었다가 현재의 판단에 사용한다. 여기서 말하는 후자가 기억이며, 이는 고등생물의 뇌의 가장복잡하며 중요한 기능 중에 하나이다. 기억은 중추신경계(CNS)안 신경세포간의 synapse연결에서 구조적 기능적 변화로부터 유발되는 것으로 알려져 있다.

특히 이 기억을 연구하는데 있어서 좋은 모델은, 중독(addiction)이다. Nicotine 또는 alcohol의 남용으로 일어나는 중독과 연관된 기억은 아주 강력하여, 약물투여를 중단한 다음에도 심지어는 평생 지속되기도 한다. 이런 이유로 중독은 언제나 재발할 위험성을 가지고 있으며, 따라서 중독에 대한 치료는 심각한 사회적 이슈이다. 그러나 이런 중독 기억의 불변, 지속성에 대해선 많이 밝혀진 것이 없다. 따라서, 중독기억형성과정에 대한 분자적, 전기생리학적, 행동적 연구를 통해 중독을 보다 효과적으로 치료할 수 있을 것으로 생각된다.

또한, 그 반대되는 양상을 띠는 공포(fear)도 기억연구에 좋은 모델이다. 이 역시 강력하며 지워지지 않는다. 공포의 기억을 완화시키기 위한 행동적 치료법조차 공포기억을 영원히 지울 수는 없다. 재발되는 공포기억의 트라우마, 또는 비적절한 공포기억으로부터 유발되는 panic disorder등은 중요한 사회적 문제이다. 본 연구실에서는 이렇게 기억에 대한 여러 가지 issue를 systems neuroscience 적 관점에서 공부하고 있음.

학생들이 참여할 수 있는 실험들을 들어보면:
- 기억유발에 따라 변화하는 neural circuit에 대한 생화학적 연구
- Cocaine self-administration 행동실험
- Brain slice를 통한 synapse간의 연결 관찰
- 공포기억의 학습화에 대한 행동실험

• ㆍMolecular mechanisms of synaptic plasticity
• ㆍMechanistic study of cell adhesion molecules
• ㆍPathophysiology of neurodegenerative and psychiatric diseases
• ㆍCell-type specific alteration of neuronal circuitry occurred by drug addiction

• ㆍKo Bum, et al., (2023) Npas4-mediated dopaminergic regulation of safety memory consolidation. Cell Reports 42(7):112678
• ㆍKwon J, et al., (2023) Rewiring of Prelimbic Inputs to the Nucleus Accumbens Core Underlies Cocaine-Induced Behavioral Sensitization. Biological Psychiatry 94(5):378
• ㆍYang YR, et al., (2017) Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior. Mol Psychiatry. Mol Psychiatry. 22(10):1473
• ㆍKwon OB, et al., (2015) Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear. Neuron 88(2):378
• ㆍBudreck EC, et al., (2013) Neuroligin-1 controls synaptic abundance of NMDA-type glutamate receptors through extracellular coupling. Proc Natl Acad Sci US A. 110(2):725
• ㆍChoi YB, et al., (2011) Neurexin-neuroligin transsynaptic interaction mediates learning-related synaptic remodeling and long-term facilitation in aplysia. Neuron 70(3):468
• ㆍKim J, et al., (2011) Cell type-specific alterations in the nucleus accumbens by repeated exposures to cocaine. Biol Psychiatry. 69(11):1026
• ㆍJung SY, et al., (2010) Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors. Proc Natl Acad Sci US A. 107(10):4710
• ㆍKim J, et al., (2008) Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals. Proc Natl Acad Sci US A. 105(26):9087

• ㆍB.S., Microbiology, Seoul National University (1992)
• ㆍM.S., Medicine, Seoul National University (1996)
• ㆍPh.D., Neurobiology, Imperial College, University of London (2000)

• ㆍ2000-2005: Postdoctoral Fellow, Columbia Univ., NY, USA.
• ㆍ2001-2004: Research associate, HHMI, NY, USA.
• ㆍ2005-2009: Assistant Professor, POSTECH
• ㆍ2010-2016: Associate professor, POSTECH
• ㆍ2016-Present: Professor, POSTECH

• ㆍFunctional roles of Neuroligin-1 in mature neural circuits
• ㆍElucidation of small GTPase mechanism to long-term memory
• ㆍStructural changes of individual synapses in synaptic plasticity
• ㆍIdentification of pathway-specific alteration of synaptic plasticity
• ㆍDrug addiction mechanism in the basal ganglia circuit
• ㆍAmygdala circuits for fear memory