• 생명과학회지
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• 제27권3호
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• pp.355-360
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• 2017

다량의 에탄올을 섭취하면 기억 상실로 이어질 수 있으며, 종종 blackout으로 나타난다. Blackout의 불균형은 알코올 소비에 있어 다양한 사회 문제의 주요 원인이 될 수 있다. 그러나 이러한 알코올 유발 문제를 예방하는 치료법은 아직 존재하지 않는다. Hydrangeae dulcis folium은 Hydrangea serrata Seringe의 잎을 발효가공을 통해 만든 민간약 또는 차이다. 본 연구에서는 에탄올로 유도한 정신적 결핍에 대한 Hydrangeae dulcis folium의 에탄올 추출물(EHDF)의 효과를 평가하였다. 행동적 결핍 또는 장애를 테스트하기 위해 마우스에서 물체 인식 테스트가 수행하였다. 또한 시냅스 결손을 평가하기 위해, 마우스 해마 조각에서 에탄올에 취약한 것으로 알려져 있고 에탄올로 유발한 기억 상실과 관련이 있는 N-methyl-D-aspartate (NMDA) 수용체-매개 흥분성 시냅스 후 전위 및 long-term potentiation (LTP)을 측정하였다. 본 연구에서 에탄올(1 g/kg, i.p.)은 물체 인식 메모리를 손상 시켰지만, EHDF (10 또는 30 mg/kg)는 물체 인식 테스트에서 이러한 장애를 극복하였다. 흥미롭게도, EHDF ($30{\mu}g/ml$)는 해마 절편에서 에탄올 처리 후 억제되었던 LTP 및 NMDA 수용체 매개 시냅스 전달을 유의하게 개선시켰다. EHDF는 에탄올에 의해 유발된 물체 인식 기억력 결핍을 개선하였고, 또한 EHDF는 해마 절편에서 에탄올 유도성 LTP 및 NMDA 수용체 매개성 시냅스 전달을 상당히 개선시켰다.

• The Korean Journal of Physiology and Pharmacology
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• 제7권2호
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• pp.59-63
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• 2003

The medial vestibular nucleus (MVN) neurons are controlled by excitatory synaptic transmission from the vestibular afferent and commissural projections, and by inhibitory transmission from interneurons. Spontaneous synaptic currents of MVN neurons were studied using whole cell patch clamp recording in slices prepared from 13- to 17-day-old rats. The spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly reduced by the $GABA_A$ antagonist bicuculline ($20{\mu}M$), but were not affected by the glycine antagonist strychnine ($1{\mu}M$). The frequency, amplitude, and decay time constant of sIPSCs were $4.3{\pm}0.9$ Hz, $18.1{\pm}2.0$ pA, and $8.9{\pm}0.4$ ms, respectively. Spontaneous excitatory postsynaptic currents (sEPSCs) were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466 ($50{\mu}M$) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. The AMPA mediated sEPSCs were characterized by low frequency ($1.5{\pm}0.4$ Hz), small amplitude ($13.9{\pm}1.9$ pA), and rapid decay kinetics ($2.8{\pm}0.2$ ms). The majority (15/21) displayed linear I-V relationships, suggesting the presence of GluR2-containing AMPA receptors. Only 35% of recorded MVN neurons showed NMDA mediated currents, which were characterized by small amplitude and low frequency. These results suggest that the MVN neurons receive excitatory inputs mediated by AMPA, but not kainate, and NMDA receptors, and inhibitory transmission mediated by $GABA_A$ receptors in neonatal rats.

• 한국정보과학회:학술대회논문집
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• 한국정보과학회 2003년도 봄 학술발표논문집 Vol.30 No.1 (B)
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• pp.416-418
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• 2003

해마 뉴런의 시냅스에서 발생하는 전류는 후시냅스의 생화학적 반응을 통해 다음 뉴런으로 전달된다. 즉, 시냅스는 정보를 전달하는 매개로서 전시냅스에서 입력된 정보에 의거하여 후시냅스로 보내는 전류량을 조절하게 된다. 본 논문에서 제안하는 시냅스 기전 신경망 모델은 기존의 신경망과는 달리 시냅스에서 일어나는 반응-확산(reaction-diffusion) 모델에 의하여 입력과 출력의 관계를 결정한다. 제안된 신경망을 분류 문제에 적용한 결과 은닉 뉴런층 없이도 좋은 성능을 보였으며, 이 신경망은 앞으로 뇌에서의 생화학적 뉴런 학습 양상을 연구하는 모델로 사용될 수 있다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.59-59
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• 1999

Circulating substances can directly access the neurons in circumventricular organ (CVO) located on the border of cerebral ventricles. The neurons in CVO are considered to playa pivotal role in blood-brain communication. In subfonical organ (SFO), a CVO in forebrain, angiotensin II (AII) is mown to reduce A type $K^{＋}$ current and input resistance, but enhance firing rate.(omitted)

• Molecules and Cells
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• 제45권5호
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• pp.306-316
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• 2022

Chronic stress contributes to the risk of developing depression; the habenula, a nucleus in epithalamus, is associated with many neuropsychiatric disorders. Using genome-wide gene expression analysis, we analyzed the transcriptome of the habenula in rats exposed to chronic restraint stress for 14 days. We identified 379 differentially expressed genes (DEGs) that were affected by chronic stress. These genes were enriched in neuroactive ligand-receptor interaction, the cAMP (cyclic adenosine monophosphate) signaling pathway, circadian entrainment, and synaptic signaling from the Kyoto Encyclopedia of Genes and Genomes pathway analysis and responded to corticosteroids, positive regulation of lipid transport, anterograde trans-synaptic signaling, and chemical synapse transmission from the Gene Ontology analysis. Based on protein-protein interaction network analysis of the DEGs, we identified neuroactive ligand-receptor interactions, circadian entrainment, and cholinergic synapse-related subclusters. Additionally, cell type and habenular regional expression of DEGs, evaluated using a recently published single-cell RNA sequencing study (GSE137478), strongly suggest that DEGs related to neuroactive ligand-receptor interaction and trans-synaptic signaling are highly enriched in medial habenular neurons. Taken together, our findings provide a valuable set of molecular targets that may play important roles in mediating the habenular response to stress and the onset of chronic stress-induced depressive behaviors.

• Journal of Korean Neurosurgical Society
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• 제42권3호
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• pp.205-210
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• 2007

Objective : Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated currents (Ih) that participate in regulating neuronal membrane potential and contribute critically to pacemaker activity, promoting synchronization of neuronal networks. However, distinct regional and cellular localization of HCN channels in the brain have not been precisely defined. Aim of this study was to verify the precise cellular location of HCN1 channels in rat cerebellum to better understand the physiological role these channels play in synaptic transmission between CNS neurons. Methods : HCN1 expression in rat brain was analyzed using immunohistochemistry and electron-microscopic observations. Postsynaptic density-95 (PSD-95), otherwise known as locating and clustering protein, was also examined to clarify its role in the subcellular location of HCN1 channels. In addition, to presume the binding of HCN1 channels with PSD-95, putative binding motifs in these channels were investigated using software-searching method. Results : HCN1 channels were locally distributed at the presynaptic terminal of basket cell and exactly corresponded with the location of PSD-95. Moreover, nine putative SH3 domain of PSD-95 binding motifs were discovered in HCN1 channels from motif analysis. Conclusion : Distinct localization of HCN1 channels in rat cerebellum is possible, especially when analyzed in conjunction with the SH3 domain of PSD-95. Considering that HCN1 channels contribute to spontaneous rhythmic action potentials, it is suggested that HCN1 channels located at the presynaptic terminal of neurons may play an important role in synaptic plasticity.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.249-255
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• 2018

Echinacoside, an active compound in the herb Herba Cistanche, has been reported to inhibit glutamate release. In this study, we investigated the effects of echinacoside on spontaneous excitatory synaptic transmission changes induced by 4-aminopyridine (4-AP), by using the in vitro rat hippocampal slice technique and whole-cell patch clamp recordings from CA3 pyramidal neurons. Perfusion with echinacoside significantly suppressed the 4-AP-induced epileptiform activity in a concentration-dependent manner. Echinacoside reduced 4-AP-induced increase in frequency of spontaneous excitatory postsynaptic currents (sEPSCs) but it did not affect the amplitude of sEPSCs or glutamate-activated currents, implicating a presynaptic mechanism of action. Echinacoside also potently blocked sustained repetitive firing, which is a basic mechanism of antiepileptic drugs. These results suggest that echinacoside exerts an antiepileptic effect on hippocampal CA3 pyramidal neurons by simultaneously decreasing glutamate release and blocking abnormal firing synchronization. Accordingly, our study provides experimental evidence that echinacoside may represent an effective pharmacological agent for treating epilepsy.

• International Journal of Oral Biology
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• 제34권4호
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• pp.215-222
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• 2009

Medial vestibular nucleus (MVN) neurons are involved in the reflex control of the head and eyes, and in the recovery of vestibular function after the formation of peripheral vestibular lesions. In our present study, whole cell patch clamp recordings were carried out on MVN neurons in brainstem slices from neonatal rats to investigate the actions of a group I metabotropic glutamate receptor (mGluR) agonist upon synaptic transmission and ionic currents. Application of the mGluR I agonist (S)-3,5- dihydroxyphenylglycine (DHPG) increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs) but had no effect upon amplitude distributions. To then identify which of mGluR subtypes is responsible for the actions of DHPG in the MVN, we employed two novel subtype selective antagonists. (S)-(+)-$\alpha$-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist of mGluR5. Both LY367385 and MPEP antagonized the DHPG-induced increase of mIPSCs, with the former being more potent. DHPG was also found to induce an inward current, which can be enhanced under depolarized conditions. This DHPG-induced current was reduced by both LY367385 and MPEP. The DHPG-induced inward current was also suppressed by the PLC blocker U-73122, the $IP_3$ receptor antagonist 2-APB, and following the depletion of the intracellular $Ca^{2+}$ pool by thapsigargin. These data suggest that the DHPG-induced inward current may be mainly regulated by the intracellular $Ca^{2+}$ store via the PLC-$IP_3$ pathway. In conclusion, mGluR I, via pre- and postsynaptic actions, may modulate the excitability of the MVN neurons.

• The Korean Journal of Physiology and Pharmacology
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• 제12권6호
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• pp.293-297
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• 2008

The effect of forskolin on corticostriatal synaptic transmission was examined by recording excitatory postsynaptic currents (EPSCs) in rat brain slices using the whole-cell voltage-clamp technique. Forskolin produced a dose-dependent increase of corticostriatal EPSCs (1, 3, 10, and $30{\mu}M$) immediately after its treatment, and the increase at 10 and $30{\mu}M$ was maintained even after its washout. When the brain slices were pre-treated with (DL)-2-amino-phosphonovaleric acid (AP-V, $100{\mu}M$), an NMDA receptor antagonist, the acute effect of forskolin ($10{\mu}M$) was blocked. However, after washout of forskolin, an increase of corticostriatal EPSCs was still observed even in the presence of AP-V. When KT 5720 ($5{\mu}M$), a protein kinase A (PKA) inhibitor, was applied through the patch pipette, forskolin ($10{\mu}M$) increased corticostriatal EPSCs, but this increase was not maintained. When forskolin was applied together with AP-V and KT 5720, both the increase and maintenance of the corticostriatal EPSCs were blocked. These results suggest that forskolin activates both NMDA receptors and PKA, however, in a different manner.

• Applied Microscopy
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• 제36권2호
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• pp.83-91
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• 2006

신경연접은 다양한 생리적 또는 병적 상태에 반응하여 구조 및 수적 변화를 보이며, 신경연접의 밀도 변화는 신경세포의 활성 조절에 중요한 역할을 하는 것으로 알려져 있다. 따라서 특정 생리적 또는 병적 상태에서 신경연접의 밀도 변화를 명확히 이해하기 위해서는 정확한 정량방법을 이용한 밀도 측정이 필수적이다. 본 연구에서는 physical disector법을 이용하여 흰쥐 뇌의 치아이랑에 위치하는 과립신경세포의 신경연접 수를 측정하였으며, 이를 통해 physical disector의 방법적 정확성을 확인하고자 하였다. 성체 흰쥐를 관류고정한 후 치아이랑의 연속 절편을 얻어 통상적인 전자현미경 시료제작법을 통해 Epon 혼합용액에 포매하였다. Physical disector법을 이용한 밀도 분석 시 연속절편의 정렬, 비교 및 disector frame이 필요하므로 Reconstruct 프로그램을 사용하였다. 동물 당 40장의 $1{\mu}m$ 연속절편을 제작하여 과립신경세포체의 밀도를 측정하였으며, 15장의 80nm연속절편으로부터 bidirectional disector법을 이용하여 과립신경세포와 내측 관통로(medial perforant path) 간 신경 연접의 밀도를 분석하였다. 과립신경세포의 세포체와 신경연접은 각각 과립층과 분자층에 위치하기 때문에 하나의 신경세포가 가지는 신경연접의 수를 측정하기 위해서는 각 층의 부피를 고려하는 것이 요구된다. 따라서 과립층에 대한 분자층의 부피비율을 측정하였다. 실험결과, 흰쥐 치아이랑에 위치하는 하나의 과립세포당 약 6,500개의 신경연접의 존재한다는 사실을 확인하였으며, 이는 다른 연구자들의 결과와 유사하였다. 본 연구로부터 physical disector법은 특정 생리적 또는 병적 조건에서 나타나는 신경세포 및 신경연접의 수적 변화를 정확히 측정할 수 있는 유용한 정량방법임을 알 수 있었다. 향후 physical disector법을 이용하여 다양한 실험동물모델의 신경연접 변화를 분석하는 것은 신경연접의 형태적 가소성을 이해하는데 이바지할 것으로 생각된다.