https://scholar.dgist.ac.kr/handle/20.500.11750/301 2026-04-04T12:48:23Z 2026-04-04T12:48:23Z Seo-Jin Oh Jin-jyeok Jang Jean-Pierre Roussarie Gyeong-un Jang Min-seok Jeong Yeon Suk Jo Chang-Hoon Shin Hongsoo Choi Kwang Lee Yoon, Jong-Hyeok Yong-Seok Oh https://scholar.dgist.ac.kr/handle/20.500.11750/59929 2026-02-05T10:40:16Z

Title: Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy Author(s): Seo-Jin Oh; Jin-jyeok Jang; Jean-Pierre Roussarie; Gyeong-un Jang; Min-seok Jeong; Yeon Suk Jo; Chang-Hoon Shin; Hongsoo Choi; Kwang Lee; Yoon, Jong-Hyeok; Yong-Seok Oh Abstract: Selective serotonin reuptake inhibitors (SSRIs) exhibit delayed therapeutic effects despite rapid serotonin elevation, suggesting their dependence on slow neuroplastic adaptations. Here, we demonstrate that antidepressant actions require cell type-specific translational regulation of the peptidergic signaling in the dentate gyrus (DG). Chronic, but not acute, treatment with an SSRI fluoxetine (FLX) selectively enhances translational activity in hilar mossy cells (MCs), with no detectable changes in neighboring granule cells (GCs). Combining Translating Ribosome Affinity Purification (TRAP) with RNA sequencing revealed distinct baseline translatomes between these two glutamatergic neurons and identified FLX-induced remodeling of peptidergic pathways in the DG. Crucially, we discovered MC-specific enrichment of the neuropeptide PACAP, which undergoes translation-dependent upregulation by chronic FLX treatment. This PACAP induction mediates neuroadaptive plasticity in PAC1 receptor-expressing GCs and drives behavioral responses prominently in female mice during prolonged FLX administration. Our findings establish cell type-specific translational reprogramming as a novel mechanistic framework for antidepressant action.

Sugiyama, Keita Kuroiwa, Mahomi Shuto, Takahide Hwang, Sehyeon Oh, Yong-Seok Nishi, Akinori https://scholar.dgist.ac.kr/handle/20.500.11750/58491 2025-07-25T02:45:15Z 2025-06-30T15:00:00Z

Title: Subregion-specific suppression of dopamine D1 receptor expression prevents L-DOPA-induced dyskinesia in a mouse model of Parkinson's disease Author(s): Sugiyama, Keita; Kuroiwa, Mahomi; Shuto, Takahide; Hwang, Sehyeon; Oh, Yong-Seok; Nishi, Akinori Abstract: L-DOPA-induced dyskinesia (LID) is a debilitating motor complication that develops following prolonged L-DOPA therapy in patients with Parkinson's disease (PD). Aberrant activation of dopamine D1 receptor (DRD1) signaling in D1-type/direct pathway medium spiny neurons (MSNs) of the striatum plays a critical role in the pathophysiology of LID. We previously characterized DRD1 signaling in seven striatal subregions and found that upregulation of DRD1 signaling in the intermediate/caudal part (IC) is associated with LID in a mouse model of PD. Here, we investigated whether DRD1 expression in the IC plays a causal role in LID development. Using an adeno-associated virus (AAV) expressing a short hairpin RNA against Drd1 (AAV-shDrd1), we selectively knocked down DRD1 expression in the IC of male mice. In unilateral 6-hydroxydopamine-lesioned mice, DRD1 knockdown in the IC significantly attenuated LID after acute and chronic L-DOPA treatment. In contrast, knockdown in either the rostral or intermediate/rostral part, previously identified as the LID-unrelated subregion, did not affect LID. These findings highlight the essential role of DRD1 and its signaling in the IC in LID development, providing valuable insights for developing novel therapeutic approaches. © 2025 Elsevier B.V.

2025-06-30T15:00:00Z Park, Jeongrak Kang, Seongtak Lee, Yaebin Choi, Ji-Woong Oh, Yong-Seok https://scholar.dgist.ac.kr/handle/20.500.11750/58442 2025-07-25T02:44:23Z 2023-12-31T15:00:00Z

Title: Continuous long-range measurement of tonic dopamine with advanced FSCV for pharmacodynamic analysis of levodopa-induced dyskinesia in Parkinson’s disease Author(s): Park, Jeongrak; Kang, Seongtak; Lee, Yaebin; Choi, Ji-Woong; Oh, Yong-Seok Abstract: Levodopa, a dopamine prodrug, alleviates the motor symptoms of Parkinson’s disease (PD), but its chronic use gives rise to levodopa-induced dyskinesia (LID). However, it remains unclear whether levodopa pharmacodynamics is altered during the progressive onset of LID. Using in vivo fast-scan cyclic voltammetry and second-derivative-based background drift removal, we continuously measured tonic dopamine levels using high temporal resolution recording over 1-h. Increases to tonic dopamine levels following acute levodopa administration were slow and marginal within the naïve PD model. However, these levels increased faster and higher in the LID model. Furthermore, we identified a strong positive correlation of dyskinetic behavior with the rate of dopamine increase, but much less with its cumulative level, at each time point. Here, we identified the altered signature of striatal DA dynamics underlying LID in PD using an advanced FSCV technique that demonstrates the long-range dynamics of tonic dopamine following drug administration. © 2024 Park, Kang, Lee, Choi and Oh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

2023-12-31T15:00:00Z Lee, Jun-Seop Park, Jeongrak Jeong, Min-Seok Oh, Seo-Jin Yoon, Jong-Hyuk Oh, Yong-Seok https://scholar.dgist.ac.kr/handle/20.500.11750/57378 2025-10-18T04:40:10Z 2024-06-30T15:00:00Z

Title: Anatomical topology of extrahippocampal projections from dorsoventral CA pyramidal neurons in mice Author(s): Lee, Jun-Seop; Park, Jeongrak; Jeong, Min-Seok; Oh, Seo-Jin; Yoon, Jong-Hyuk; Oh, Yong-Seok Abstract: The hippocampus primarily functions through a canonical trisynaptic circuit, comprised of dentate granule cells and CA1-CA3 pyramidal neurons (PNs), which exhibit significant heterogeneity along the dorsoventral axis. Among these, CA PNs are known to project beyond the hippocampus into various limbic areas, critically influencing cognitive and affective behaviors. Despite accumulating evidence of these extrahippocampal projections, the specific topological patterns—particularly variations among CA PN types and between their dorsal and ventral subpopulations within each type—remain to be fully elucidated. In this study, we utilized cell type-specific Cre mice injected with fluorescent protein-expressing AAVs to label each CA PN type distinctly. This method further enabled the dual-fluorescence labeling of dorsal and ventral subpopulations using EGFP and tdTomato, respectively, allowing a comprehensive comparison of their axonal projections in an animal. Our findings demonstrate that CA1 PNs predominantly form unilateral projections to the frontal cortex (PFC), amygdala (Amy), nucleus accumbens (NAc), and lateral septum (LS), unlike CA2 and CA3 PNs making bilateral innervation to the LS only. Moreover, the innervation patterns especially within LS subfields differ according to the CA PN type and their location along the dorsoventral axis of the hippocampus. This detailed topographical mapping provides the neuroanatomical basis of the underlying functional distinctions among CA PN types. Copyright © 2024 Lee, Park, Jeong, Oh, Yoon and Oh.

2024-06-30T15:00:00Z