• The Korean Journal of Physiology and Pharmacology
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• 제10권2호
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• pp.59-64
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• 2006

The effects of $Zn^{2+}$ on spontaneous glutamate and GABA release were tested in mechanically dissociated rat CA3 pyramidal neurons which retained functional presynaptic nerve terminals. The spontaneous miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) were pharmacologically isolated and recorded using whole-cell patch clamp technique under voltage-clamp conditions. $Zn^{2+}$ at a lower concentration $(30{\mu}M)$ increased GABAergic mIPSC frequency without affecting mIPSC amplitude, but it decreased both mIPSC frequency and amplitude at higher concentrations $({\ge}300{\mu}M)$. In contrast, $Zn^{2+}$ (3 to $100{\mu}M$) did not affect glutamatergic mEPSCs, although it slightly decreased both mIPSC frequency and amplitude at $300{\mu}M$ concentration. Facilitatory effect of $Zn^{2+}$ on GABAergic mIPSC frequency was occluded either in $Ca^{2+}$-free external solution or in the presence of $100{\mu}M$ 4-aminopyridine, a non-selective $K^{+}$ channel blocker. The results suggest that $Zn^{2+}$ at lower concentrations depolarizes GABAergic nerve terminals by blocking $K^{+}$ channels and increases the probability of spontaneous GABA release. This $Zn^{2+}$-mediated modulation of spontaneous GABAergic transmission is likely to play an important role in the regulation of neuronal excitability within the hippocampal CA3 area.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.303-307
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• 2006

The effects of ethanol on corticostriatal synaptic transmission were examined, using extracellular recording and analysis of population spike amplitudes in rat brain slices, to study how acute ethanol intoxication impairs striatal function. Ethanol caused a decrease in population spike amplitudes in a dose dependent manner ($50{\sim}200mM$). Pretreatment with picrotoxin, a ${\gamma}-amino$ butyric acid $(GABA)_{A}$ receptor antagonist, increased the population spikes but ethanol (100 mM) was still effective in decreasing the population spikes under this condition. In the presence of $_{(DL)}-2-amino-5-phosphonovaleric$ acid (APV), N-methyl-D-aspartate (NMDA) receptor antagonist, the inhibitory action of ethanol on population spikes was not shown. These results suggest that ethanol inhibits the glutamatergic corticostriatal synaptic transmission through blockade of NMDA receptors.

• 대한불안의학회지
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• 제6권1호
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• pp.31-36
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• 2010

Objective : Mismatch negativity (MMN) provides an electrophysiological index of an involuntary attention switching process. This study investigated MMN anomalies and their relationship to clinical variables in patients with obsessive-compulsive disorder (OCD). Methods : Study participants were 29 OCD patients and 24 normal controls. We used a 128-channel EEG to measure MMN during a passive oddball paradigm. Then we assessed the correlations between MMN amplitudes and clinical measures. Results : The OCD patients exhibited significantly greater MMN amplitude compared to the controls. Also, the right frontal lobe MMN amplitudes correlated significantly to the OCD patients' Yale-Brown Obsessive Compulsive Scale total scores (r=-0.520, p=0.005). Conclusion : These results suggest that MMN anomalies in OCD patients reflect a monitoring circuit dysfunction, raising the possibility that the OCD's pathophysiology includes glutamatergic dysfunction.

• Psychiatry investigation
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• 제15권12호
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• pp.1130-1134
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• 2018

Objective Trichotillomania is a relatively common illness whose neurobiology is poorly understood. One treatment for adult trichotillomania, n-acetyl cysteine (NAC), has antioxidative properties, as well as effects on central glutamatergic transmission. Preclinical models suggest that excessive oxidative stress may be involved in its pathophysiology. Methods Adults with trichotillomania provided a blood sample for analysis of compounds that may be influenced by oxidative stress [glutathione, angiotensin II, ferritin, iron, glucose, insulin and insulin growth factor 1 (IGF1), and hepcidin]. Participants were examined on symptom severity, disability, and impulsivity. The number of participants with out-of-reference range oxidative stress measures were compared against the null distribution. Correlations between oxidative stress markers and clinical measures were examined. Results Of 14 participants (mean age 31.2 years; 92.9% female), 35.7% (n=5) had total glutathione levels below the reference range (p=0.041). Other oxidative stress measures did not have significant proportions outside the reference ranges. Lower levels of glutathione correlated significantly with higher motor impulsiveness (Barratt Impulsiveness Scale sub-score) (r=0.97, p=0.001). Conclusion A third of patients with trichotillomania had low levels of glutathione, and lower levels of glutathione correlated significantly with higher motor impulsiveness. Because NAC is a precursor for cysteine, and cysteine is a rate limiting step for glutathione production, these results may shed light on the mechanisms through which NAC can have beneficial effects for impulsive symptoms. Confirmation of these results requires a suitable larger follow-up study, including an internal normative control group.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.62-66
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• 2018

A-type $K^+$ ($I_A$) channels are transiently activated in the suprathreshold membrane potential and then rapidly inactivated. These channels play roles to control the neuronal excitability in pyramidal neurons in hippocampi. We here electrophysiologically tested if regulatory functions of $I_A$ channels might be targeted by acute activation of glutamatergic synaptic transmission in cultured hippocampal neurons(DIV 6~8). The application of high KCl in recording solutions(10 mM, 2 min) to increase presynaptic glutamate release, significantly reduced the peak of somatic $I_A$ without changes of gating kinetics. This indicates that neuronal excitation induced by the enhancement of synaptic transmission may process with distinctive signaling cascades to affect voltage-dependent ion channels in hippocampal neurons. Therefore, it is possible that short-lasting enhancement of synaptic transmission is functionally restricted in local synapses without effects on intracellular signaling cascades affecting a whole neuron, efficiently and rapidly enhancing synaptic functions in hippocampal network.

• The Korean Journal of Physiology and Pharmacology
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• 제28권2호
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• pp.165-181
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• 2024

The slow and regular pacemaking activity of midbrain dopamine (DA) neurons requires proper spatial organization of the excitable elements between the soma and dendritic compartments, but the somatodendritic organization is not clear. Here, we show that the dynamic interaction between the soma and multiple proximal dendritic compartments (PDCs) generates the slow pacemaking activity in DA neurons. In multipolar DA neurons, spontaneous action potentials (sAPs) consistently originate from the axon-bearing dendrite. However, when the axon initial segment was disabled, sAPs emerge randomly from various primary PDCs, indicating that multiple PDCs drive pacemaking. Ca²⁺ measurements and local stimulation/perturbation experiments suggest that the soma serves as a stably-oscillating inertial compartment, while multiple PDCs exhibit stochastic fluctuations and high excitability. Despite the stochastic and excitable nature of PDCs, their activities are balanced by the large centrally-connected inertial soma, resulting in the slow synchronized pacemaking rhythm. Furthermore, our electrophysiological experiments indicate that the soma and PDCs, with distinct characteristics, play different roles in glutamate-induced burst-pause firing patterns. Excitable PDCs mediate excitatory burst responses to glutamate, while the large inertial soma determines inhibitory pause responses to glutamate. Therefore, we could conclude that this somatodendritic organization serves as a common foundation for both pacemaker activity and evoked firing patterns in midbrain DA neurons.

• Journal of Korean Neurosurgical Society
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• 제46권1호
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• pp.1-4
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• 2009

Objective: To report an unsuspected adaptive plasticity of single upper motor neurons and of primary motor cortex found after microsurgical connection of the spinal cord with peripheral nerve via grafts in paraplegics and focussed discussion of the reviewed literature. Methods: The research aimed at making paraplegics walk again, after 20 years of experimental surgery in animals. Amongst other things, animal experiments demonstrated the alteration of the motor endplates receptors from cholinergic to glutamatergic induced by connection with upper motor neurons. The same paradigm was successfully performed in paraplegic humans. The nerve grafts were put into the ventral-lateral spinal tract randomly, with out possibility of choosing the axons coming from different areas of the motor cortex. Results: The patient became able to selectively activate the re-innervated muscles she wanted without concurrent activities of other muscles connected with the same cortical areas. Conclusion: Authors believe that unlike in nerve or tendon transfers, where the whole cortical area corresponding to the transfer changes its function a phenomenon that we call "brain plasticity by areas". in our paradigm due to the direct connection of upper motor neurons with different peripheral nerves and muscles via nerve grafts motor learning occurs based on adaptive neuronal plasticity so that simultaneous contractions of other muscles are prevented. We propose to call it adaptive functional "plasticity by single neurons". We speculate that this phenomenon is due to the simultaneous activation of neurons spread in different cortical areas for a given specific movement, whilst the other neurons of the same areas connected with peripheral nerves of different muscles are not activated at the same time. Why different neurons of the same area fire at different times according to different voluntary demands remains to be discovered. We are committed to solve this enigma hereafter.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.673-679
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• 1997

It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induces release of neurotransmitters, including norepinephrine(NE), in ischemic milieu. In the present study, the role of nitric oxide(NO) in the ischemia-induced $[^3H]norepinephrine([^3H]NE)$ release from cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from $Mg^{2+}-free$ artificial cerebrospinal fluid, induced significant release of $[^3H]NE$ from cortex slices. This ischemia-induced $[^3H]NE$ release was significantly attenuated by glutamatergic neurotransmission modifiers. $N^G-nitro-L-arginine$ methyl ester(L-NAME), $N^G-monomethyl-L-arginine$ (L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors attenuated the ischemia-evoked $[^3H]NE$ release. Hemoglobin, a NO chelator, and 5, 5- dimethyl-L-pyrroline-N-oxide(DMPO), an electron spin trap, inhibited $[^3H]NE$ release dose-dependently. Ischemia-evoked $[^3H]NE$ release was inhibited by methylene blue, a soluble guanylate cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These results suggest that the ischemia-evoked $[^3H]NE$ release is mediated by NMDA receptors, and activation of NO system is involved.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.209-214
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• 2009

The striatum receives glutamatergic afferents from the cortex and thalamus, and these synaptic transmissions are mediated by ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl D-aspartate (NMDA) receptors. The purpose of this study was to characterize glutamate receptors by analyzing NMDA/AMPA ratio and rectification of AMPA and NMDA excitatory postsynaptic currents (EPSCs) using a whole-cell voltage-clamp method in the dorsal striatum. Receptor antagonists were used to isolate receptor or subunit specific EPSC, such as (DL)-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, ifenprodil, an NR2B antagonist, CNQX, an AMPA receptor antagonist and IEM-1460, a GluR2-lacking AMPA receptor blocker. AMPA and NMDA EPSCs were recorded at - 70 and + 40 mV, respectively. Rectification index was calculated by current ratio of EPSCs between + 50 and - 50 mV. NMDA/AMPA ratio was 0.20${\pm}$0.05, AMPA receptor ratio of GluR2-lacking/GluR2-containing subunit was 0.26${\pm}$0.05 and NMDA receptor ratio of NR2B/NR2A subunit was 0.32${\pm}$0.03. The rectification index (control 2.39${\pm}$0.27) was decreased in the presence of both APV and combination of APV and IEM-1460 (1.02${\pm}$0.11 and 0.93${\pm}$0.09, respectively). These results suggest that the major components of the striatal glutamate receptors are GluR2-containing AMPA receptors and NR2A-containing NMDA receptors. Our results may provide useful information for corticostriatal synaptic transmission and plasticity studies.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.195-200
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• 2009

Zinc released from excited glutamatergic neurons accelerates amyloid ${\beta}$ (A ${\beta}$) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter A ${\beta}$ concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed A ${\beta}$ production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased A ${\beta}$ 40 and A ${\beta}$ 42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both ${\beta}$-and ${\alpha}$-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of A ${\beta}$ 40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of A ${\beta}$ secretion.