Hyoung-Gon Ko

Bio: Hyoung-Gon Ko is an academic researcher from Kyungpook National University. The author has contributed to research in topics: Synaptic plasticity & Long-term potentiation. The author has an hindex of 10, co-authored 19 publications receiving 806 citations. Previous affiliations of Hyoung-Gon Ko include UPRRP College of Natural Sciences & Xi'an Jiaotong University.

Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex

Abstract: Synaptic plasticity is a key mechanism for chronic pain It occurs at different levels of the central nervous system, including spinal cord and cortex Studies have mainly focused on signaling proteins that trigger these plastic changes, whereas few have addressed the maintenance of plastic changes related to chronic pain We found that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the mouse anterior cingulate cortex (ACC) Peripheral nerve injury caused activation of PKMζ in the ACC, and inhibiting PKMζ by a selective inhibitor, ζ-pseudosubstrate inhibitory peptide (ZIP), erased synaptic potentiation Microinjection of ZIP into the ACC blocked behavioral sensitization These results suggest that PKMζ in the ACC acts to maintain neuropathic pain PKMζ could thus be a new therapeutic target for treating chronic pain

Interregional synaptic maps among engram cells underlie memory formation

Abstract: Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation.

Induction of Neuronal Vascular Endothelial Growth Factor Expression by cAMP in the Dentate Gyrus of the Hippocampus Is Required for Antidepressant-Like Behaviors

Abstract: The cAMP cascade and vascular endothelial growth factor (VEGF) are critical modulators of depression. Here we have tested whether the antidepressive effect of the cAMP cascade is mediated by VEGF in the adult hippocampus. We used a conditional genetic system in which the Aplysia octopamine receptor (Ap oa1), a Gs-coupled receptor, is transgenically expressed in the forebrain neurons of mice. Chronic activation of the heterologous Ap oa1 by its natural ligand evoked antidepressant-like behaviors, accompanied by enhanced phosphorylation of cAMP response element-binding protein and transcription of VEGF in hippocampal dentate gyrus (DG) neurons. Selective knockdown of VEGF in these cells during the period of cAMP elevation inhibited the antidepressant-like behaviors. These findings reveal a molecular interaction between the cAMP cascade and VEGF expression, and the pronounced behavioral consequences of this interaction shed light on the mechanism underlying neuronal VEGF functions in antidepression.

Plasticity of Metabotropic Glutamate Receptor-Dependent Long-Term Depression in the Anterior Cingulate Cortex after Amputation

Abstract: Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results provide in vitro evidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.

The molecular biology of memory: CAMP, PKA, CRE, CREB-1, CREB-2, and CPEB

Abstract: The analysis of the contributions to synaptic plasticity and memory of cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB has recruited the efforts of many laboratories all over the world. These are six key steps in the molecular biological delineation of short-term memory and its conversion to long-term memory for both implicit (procedural) and explicit (declarative) memory. I here first trace the background for the clinical and behavioral studies of implicit memory that made a molecular biology of memory storage possible, and then detail the discovery and early history of these six molecular steps and their roles in explicit memory.

Chronic pain-related remodeling of cerebral cortex – ‘pain memory’: a possible target for treatment of chronic pain

Abstract: SUMMARY Chronic pain is a major health problem worldwide, yet its management is nonspecific and often insufficient. In order to be able to alleviate chronic pain, it is crucial to understand the profound and comprehensive mechanisms by which chronic pain is triggered and processed in higher brain areas. Painful stimuli are processed by an intricate axis of peripheral and central components. Adding to the inherent complexity, the system is highly dynamic, undergoing constant plastic changes that often lead to perpetuation of pain. Given the key role that the cerebral cortex plays in sensory perception, understanding pain-related changes in cortical areas allocated to pain sensation is crucial. This review aims to summarize present research on pain-related plastic changes in the cerebral cortex.