• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.303-306
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• 2003

Metabotropic glutamate receptors (mGluRs), classified into three groups (group I, II, III), play a critical role in modulation of synaptic transmission at central and peripheral synapses. In the present study, extracellular field potential recording techniques were used to investigate effects of mGluR agonists on excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. The non-selective mGluR agonist t-ACPD ($100{\mu}M$) produced reversible, short-term depression, but the group III mGluR agonist L-AP4 ($50{\mu}M$) did not have any significant effects on amygdala synaptic transmission, suggesting that group I and/or II mGluRs are involved in the modulation by t-ACPD. The group I mGluR agonist DHPG ($100{\mu}M$) produced reversible inhibition as did t-ACPD. Unexpectedly, the group II mGluR agonist LCCG-1 ($10{\mu}M$) induced long-term as well as short-term depression. Thus, our data suggest that activation of group I or II mGluRs produces short-term, reversible depression of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. Considering the long-term effect upon activation of group II mGluRs, lack of long-term effects upon activation of group I and II mGluRs may indicate a possible cross-talk among different groups of mGluRs.

• Journal of Medicine and Life Science
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• v.15 no.2
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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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• v.7 no.6
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• pp.295-301
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• 2003

Striatum plays a crucial role in the movement control and habitual learning. It receives an information from wide area of cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from raphe nuclei. In the present study, the effects of 5-HT to modulate synaptic transmission were studied in the rat corticostriatal brain slice using in vitro extracellular recording technique. Synaptic responses were evoked by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. 5-HT reversibly inhibited coticostriatal glutamatergic synaptic transmission in a dose-dependent fashion (5, 10, 50, and $10{\mu}M$), maximally reducing in the corticostriatal population spike (PS) amplitude to $40.1{\pm}5.0$% at a concentration of $50{\mu}M$ 5-HT. PSs mediated by non-NMDA glutamate receptors, which were isolated by bath application of the NMDA receptor antagonist, d,l-2-amino-5-phospohonovaleric acid (AP-V), were decreased by application of $50{\mu}M$ 5-HT. However, PSs mediated by NMDA receptors, that were activated by application of zero $Mg^{2+}$ aCSF, were not significantly affected by $50{\mu}M$ 5-HT. To test whether the corticostriatal synaptic inhibitions by 5-HT might involve a change in the probability of neurotransmitter release from presynaptic nerve terminals, we measured the paired-pulse ratio (PPR) evoked by 2 identical pulses (50 ms interpulse interval), and found that PPR was increased ($33.4{\pm}5.2$%) by 5-HT, reflecting decreased neurotransmitter releasing probability. These results suggest that 5-HT may decrease neurotransmitter release probability of glutamatergic corticostriatal synapse and may be able to selectively decrease non-NMDA glutamate receptor-mediated synaptic transmission.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.317-328
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• 2019

It is known that top-down associative inputs terminate on distal apical dendrites in layer 1 while bottom-up sensory inputs terminate on perisomatic dendrites of layer 2/3 pyramidal neurons (L2/3 PyNs) in primary sensory cortex. Since studies on synaptic transmission in layer 1 are sparse, we investigated the basic properties and cholinergic modulation of synaptic transmission in layer 1 and compared them to those in perisomatic dendrites of L2/3 PyNs of rat primary visual cortex. Using extracellular stimulations of layer 1 and layer 4, we evoked excitatory postsynaptic current/potential in synapses in distal apical dendrites (L1-EPSC/L1-EPSP) and those in perisomatic dendrites (L4-EPSC/L4-EPSP), respectively. Kinetics of L1-EPSC was slower than that of L4-EPSC. L1-EPSC showed presynaptic depression while L4-EPSC was facilitating. In contrast, inhibitory postsynaptic currents showed similar paired-pulse ratio between layer 1 and layer 4 stimulations with depression only at 100 Hz. Cholinergic stimulation induced presynaptic depression by activating muscarinic receptors in excitatory and inhibitory synapses to similar extents in both inputs. However, nicotinic stimulation enhanced excitatory synaptic transmission by ~20% in L4-EPSC. Rectification index of AMPA receptors and AMPA/NMDA ratio were similar between synapses in distal apical and perisomatic dendrites. These results provide basic properties and cholinergic modulation of synaptic transmission between distal apical and perisomatic dendrites in L2/3 PyNs of the visual cortex, which might be important for controlling information processing balance depending on attentional state.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.263-268
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• 2005

Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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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.

• Korean Journal of Biological Psychiatry
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• v.20 no.1
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• pp.1-5
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• 2013

Glutamate receptors are important components of synaptic transmission in the nervous system. Especially, ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate most abundant excitatory synaptic transmission in the brain. There is elaborate mechanism of regulation of AMPA receptors including protein synthesis/degradation, intracellular trafficking, exocytosis/endocytosis and protein modification. In recent studies, it is revealed that functional dysregulation of AMPA receptors are related to major psychiatric disorders. In this review, we describe the structure and function of AMPA receptors in the synapse. We will introduce three steps of mechanism involving trafficking of AMPA receptors to neuronal membrane, lateral diffusion into synapses and synaptic retention by membrane proteins and postsynaptic scaffold proteins. Lastly, we will describe recent studies showing that regulation of AMPA receptors is important pathophysiological mechanism in psychiatric disorders.

• BMB Reports
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• v.42 no.1
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• pp.1-5
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• 2009

Synaptic vesicles (SVs) are key structures for synaptic transmission in neurons. Numerous membrane-associated proteins are sorted from the Golgi complex to the axon and the presynaptic terminal. Protein-protein and protein-lipid interactions are involved with SV targeting in neurons. Interestingly, many SV proteins have lipid binding capability, primarily with either cholesterol or phosphoinositides (PIs). As examples, the major SV protein synaptophysin can bind to cholesterol, a major lipid component in SVs, while several other SV proteins, including synaptotagmin, can bind to PIs. Thus, lipid-protein binding plays a key role for the SV targeting of synaptic proteins. In addition, numerous SV proteins can be palmitoylated. Palmitoylation is thought to be another synaptic targeting signal. Here, we briefly describe the relationship between lipid binding and SV targeting.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.461-467
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• 2009

The auditory cortex (A1) encodes the acquired significance of sound for the perception and interpretation of sound. Nitric oxide (NO) is a gas molecule with free radical properties that functions as a transmitter molecule and can alter neural activity without direct synaptic connections. We used whole-cell recordings under voltage clamp to investigate the effect of NO on spontaneous GABAergic synaptic transmission in mechanically isolated rat auditory cortical neurons preserving functional presynaptic nerve terminals. GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) in the A1 were completely blocked by bicuculline. The NO donor, S-nitroso-N-acetylpenicillamine (SNAP), reduced the GABAergic sIPSC frequency without affecting the mean current amplitude. The SNAP-induced inhibition of sIPSC frequency was mimicked by 8-bromoguanosine cyclic 3',5'-monophosphate, a membrane permeable cyclic-GMP analogue, and blocked by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, a specific NO scavenger. Blockade of presynaptic $K^+$ channels by 4-aminopyridine, a $K^+$ channel blocker, increased the frequencies of GABAergic sIPSCs, but did not affect the inhibitory effects of SNAP. However, blocking of presynaptic $Ca^{2+}$ channels by $Cd^{2+}$, a general voltage-dependent $Ca^{2+}$ channel blocker, decreased the frequencies of GABAergic sIPSCs, and blocked SNAP-induced reduction of sIPSC frequency. These findings suggest that NO inhibits spontaneous GABA release by activation of cGMP-dependent signaling and inhibition of presynaptic $Ca^{2+}$ channels in the presynaptic nerve terminals of A1 neurons.

• Molecules and Cells
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• v.25 no.1
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• pp.7-19
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• 2008

Complexins play a critical role in the control of fast synchronous neurotransmitter release. They operate by binding to trimeric SNARE complexes consisting of the vesicle protein Synaptobrevin and the plasma membrane proteins Syntaxin and SNAP-25, which are key executors of membrane fusion reactions. SNARE complex binding by Complexins is thought to stabilize and clamp the SNARE complex in a highly fusogenic state, thereby providing a pool of readily releasable synaptic vesicles that can be released quickly and synchronously in response to an action potential and the concomitant increase in intra-synaptic $Ca^{2+}$ levels. Genetic elimination of Complexins from mammalian neurons causes a strong reduction in evoked neurotransmitter release, and altered Complexin expression levels with consequent deficits in synaptic transmission were suggested to contribute to the etiology or pathogenesis of schizophrenia, Huntington's disease, depression, bipolar disorder, Parkinson's disease, Alzheimer's disease, traumatic brain injury, Wernicke's encephalopathy, and fetal alcohol syndrome. In the present review I provide a summary of available data on the role of altered Complexin expression in brain diseases. On aggregate, the available information indicates that altered Complexin expression levels are unlikely to have a causal role in the etiology of the disorders that they have been implicated in, but that they may contribute to the corresponding symptoms.