https://scholar.dgist.ac.kr/handle/20.500.11750/1206 2026-06-04T03:01:56Z https://scholar.dgist.ac.kr/handle/20.500.11750/60358 Title: Juvenile-to-adult refinement of thalamic reticular circuits via LRRTM3 enables high-resolution sensory encoding Author(s): Lee, Dongsu; Han, Kyung Ah; Jeong, Hyeonyeong; Ha, Go Eun; Lee, Hyeongjin; Kim, Beom Soo; Park, Chanmi; Piao, Yao; Lee, Haeun; Kim, Joon; Yoon, Taek Han; Kim, Seungjoon; Kim, Byeongchan; Shin, Jungsu; Cho, Yujin; Kang, Sunghyun; Park, Han-Eol; Um, Ji Won; Sohn, Chang Ho; Huguenard, John R.; Ko, Jaewon; Cheong, Eunji Abstract: Sensory processing enables adaptive behavior by accurately encoding dynamic environmental stimuli. Within thalamocortical (TC) circuits, the thalamic reticular nucleus (TRN) functions as a key inhibitory gate that regulates cortical access to sensory input. While classical models posit that sensory circuits stabilize after early critical periods, we uncover a previously unrecognized phase of synaptic refinement in TRN circuitry extending from the juvenile period into adulthood. This late-stage remodeling is driven by a progressive reduction in corticothalamic (CT) excitatory input and is essential for enhancing sensory gain, response linearity, and stimulus discriminability. We identify LRRTM3, a TRN-enriched synaptic adhesion molecule, as a molecular gatekeeper of this process. TRN-specific deletion of LRRTM3 disrupts CT–TRN refinement, elevates TRN-mediated inhibition, and impairs fine tactile discrimination. These findings revise canonical views of sensory circuit maturation, revealing that LRRTM3-mediated juvenile-to-adult TRN plasticity is essential for the emergence of high-resolution sensory encoding in the adult brain. 2026-03-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60207 Title: A decade of progress in understanding LRRTM and Slitrk synaptic cell-adhesion molecules Author(s): Kim, Dongwook; Kim, Byeongchan; Um, Ji Won; Ko, Jaewon Abstract: For over a decade, synaptic cell-adhesion molecules (CAMs) have been recognized as fundamental determinants of neural circuit specificity and diversity. Among the CAMs, leucine-rich repeat (LRR)-containing transmembrane proteins have been established as crucial regulators of synaptic properties across diverse cell-types and brain regions. This minireview focuses on two families of LRR-containing CAMs: leucine-rich repeat transmembrane proteins (LRRTMs) and the Slit and Trk-like family (Slitrks). We provide a comprehensive synthesis of significant findings on LRRTMs and Slitrks since their initial characterization more than 15 years ago. Furthermore, we outline key unresolved questions to stimulate future studies on their functional mechanisms in neural circuit assembly and their pathophysiological roles in various neurological disorders. 2026-02-28T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60198 Title: A decade of discovery: Deciphering the synaptic adhesion code Author(s): Ko, Jaewon 2026-04-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59935 Title: Neuronal mitochondrial disaggregase CLPB ameliorates Huntington's disease pathology in mice Author(s): Kim, Hyeonho; Hyun, Gaeun; Kim, Seunghye; Yu, Changmo; Hong, Young-gi; Yu, Jihyeon; Bae, Sangsu; Rhee, Hyun-Woo; Ko, Jaewon; Um, Ji Won Abstract: Background: Huntington's disease (HD) is a devastating neurodegenerative disorder caused by CAG repeat expansion in the HTT gene, resulting in a polyglutamine-expanded huntingtin (HTT) protein that forms toxic aggregates. Although heat-shock proteins are known to facilitate the refolding or clearance of misfolded proteins, their precise role in modulating protein aggregation in HD remains unclear. Here, we explore the function of caseinolytic peptidase B (ClpB), a mitochondrial AAA+ ATPase and heat-shock protein, in maintaining proteostasis and synaptic integrity in HD. Methods: We examined how CLPB loss or overexpression in human embryonic kidney 293T (HEK293T) cells impacted the aggregation of wild-type HTT (HTT-Q23) and mutant HTT (HTT-Q79). In parallel, AAV-mediated ClpB knockdown or overexpression was applied to the striatum of HD model mice. and HTT aggregation and inhibitory synaptic alterations were assessed. Aggregate burden was quantified via immunostaining, and inhibitory synapse density was evaluated using VGAT immunohistochemistry and electrophysiological recordings. Results: In HEK293T cells, CLPB knockout led to abnormal aggregation of HTT-Q23 while CLPB overexpression reduced the size of HTT-Q79 aggregates. In the mouse striatum, ClpB knockdown increased HTT-Q23 aggregate numbers and altered HTT-Q79 aggregation morphology, whereas CLPB overexpression restored the density and size of VGAT-positive inhibitory synapses and improved inhibitory synaptic transmission in HD model mice. These effects of CLPB overexpression were associated with a reduced mitochondrial aggregation burden, suggesting that ClpB contributes to mitochondrial protein quality control. Conclusions: These results demonstrate that ClpB regulates both physiological and pathological HTT aggregation and contributes to maintaining inhibitory synaptic integrity. By modulating mitochondrial proteostasis, ClpB acts as a protective factor in HD pathology, highlighting its potential as a therapeutic target for neurodegenerative disorders characterized by protein misfolding. 2025-12-31T15:00:00Z