• Molecules and Cells
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• v.21 no.1
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• pp.34-41
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• 2006

The neuronal localization of alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor (GluR) subunits is vital as they play key roles in the regulation of calcium permeability. We have examined the distribution of the calcium permeable AMPA glutamate receptor subunit GluR1 in the mouse visual cortex immunocytochemically. We compared this distribution to that of the calcium-binding proteins calbindin D28K, calretinin, and parvalbumin, and of GABA. The highest density of GluR1-immunoreactive (IR) neurons was found in layers II/III. Enucleation appeared to have no effect on the distribution of GluR1-IR neurons. The labeled neurons varied in morphology; the majority were round or oval and no pyramidal cells were labeled by the antibody. Two-color immunofluorescence revealed that 26.27%, 10.65%, and 40.31% of the GluR1-IR cells also contained, respectively, calbindin D28K, calretinin, and parvalbumin. 20.74% of the GluR1-IR neurons also expressed GABA. These results indicate that many neurons that express calcium-permeable GluR1 also express calcium binding proteins. They also demonstrate that one fifth of the GluR1-IR neurons in the mouse visual cortex are GABAergic interneurons.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.523-531
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• 2015

Serotonin [5-hydroxytryptamine (5-HT)] regulates synaptic plasticity in the visual cortex. Although the effects of 5-HT on plasticity showed huge diversity depending on the ages of animals and species, it has been unclear how 5-HT can show such diverse effects. In the rat visual cortex, 5-HT suppressed long-term potentiation (LTP) at 5 weeks but enhanced LTP at 8 weeks. We speculated that this difference may originate from differential regulation of neurotransmission by 5-HT between the age groups. Thus, we investigated the effects of 5-HT on apha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-, ${\gamma}$-aminobutyric acid receptor type A (GABAAR)-, and N-methyl-D-aspartic acid receptor (NMDAR)-mediated neurotransmissions and their involvement in the differential regulation of plasticity between 5 and 8 weeks. AMPAR-mediated currents were not affected by 5-HT at both 5 and 8 weeks. GABAAR-mediated currents were enhanced by 5-HT at both age groups. However, 5-HT enhanced NMDAR-mediated currents only at 8 weeks. The enhancement of NMDAR-mediated currents appeared to be mediated by the enhanced function of GluN2B subunit-containing NMDAR. The enhanced GABAAR- and NMDAR-mediated neurotransmissions were responsible for the suppression of LTP at 5 weeks and the facilitation of LTP at 8 weeks, respectively. These results indicate that the effects of 5-HT on neurotransmission change with development, and the changes may underlie the differential regulation of synaptic plasticity between different age groups. Thus, the developmental changes in 5-HT function should be carefully considered while investigating the 5-HT-mediated metaplastic control of the cortical network.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.517-524
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• 2014

Phasic and tonic ${\gamma}$-aminobutyric acidA ($GABA_A$) receptor-mediated inhibition critically regulate neuronal information processing. As these two inhibitory modalities have distinctive features in their receptor composition, subcellular localization of receptors, and the timing of receptor activation, it has been thought that they might exert distinct roles, if not completely separable, in the regulation of neuronal function. Inhibition should be maintained and regulated depending on changes in network activity, since maintenance of excitation-inhibition balance is essential for proper functioning of the nervous system. In the present study, we investigated how phasic and tonic inhibition are maintained and regulated by different signaling cascades. Inhibitory postsynaptic currents were measured as either electrically evoked events or spontaneous events to investigate regulation of phasic inhibition in layer 2/3 pyramidal neurons of the rat visual cortex. Tonic inhibition was assessed as changes in holding currents by the application of the $GABA_A$ receptor blocker bicuculline. Basal tone of phasic inhibition was maintained by intracellular $Ca^{2+}$ and $Ca^{2+}$/calmodulin-dependent protein kinase II (CaMKII). However, maintenance of tonic inhibition relied on protein kinase A activity. Depolarization of membrane potential (5 min of 0 mV holding) potentiated phasic inhibition via $Ca^{2+}$ and CaMKII but tonic inhibition was not affected. Thus, phasic and tonic inhibition seem to be independently maintained and regulated by different signaling cascades in the same cell. These results suggest that neuromodulatory signals might differentially regulate phasic and tonic inhibition in response to changes in brain states.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.399-405
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• 2010

Gamma-aminobutyric acid (GABA)-ergic inhibition is important in the function of the visual cortex. In a previous study, we reported a developmental increase in $GABA_A$ receptor-mediated inhibition in the rat visual cortex from 3 to 5 weeks of age. Because this developmental increase is crucial to the regulation of the induction of long-term synaptic plasticity, in the present study we investigated in detail the postnatal development of phasic and tonic inhibition. The amplitude of phasic inhibition evoked by electrical stimulation increased during development from 3 to 8 weeks of age, and the peak time and decay kinetics of inhibitory postsynaptic potential (IPSP) and current (IPSC) slowed progressively. Since the membrane time constant decreased during this period, passive membrane properties might not be involved in the kinetic changes of IPSP and IPSC. Tonic inhibition, another mode of $GABA_A$ receptor-mediated inhibition, also increased developmentally and reached a plateau at 5 weeks of age. These results indicate that the time course of the postnatal development of GABAergic inhibition matched well that of the functional maturation of the visual cortex. Thus, the present study provides significant insight into the roles of inhibitory development in the functional maturation of the visual cortical circuits.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.469-473
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• 2009

Induced activation of the gamma-aminobutyric $acid_A$ ($GABA_A$) receptor in the retina of goldfish caused the fish to rotate in the opposite direction to that of the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a $GABA_A$ receptor agonist, modified OMR in a concentration-dependent manner. The $GABA_B$ receptor agonist baclofen and $GABA_C$ receptor agonist CACA did not affect OMR. The observed modifications in OMR included decreased anterograde rotation $(0.01\sim0.03\;{\mu}M)$, coexistence of retrograde rotation and decreased anterograde rotation $(0.1\sim30\;{\mu}M)$ and only retrograde rotation $(100\;{\mu}M\sim1\;mM)$. In contrast, the $GABA_A$ receptor antagonist bicuculline blocked muscimol-induced retrograde rotation. Based on these results, we inferred that the coding inducing retrograde movement of the goldfish retina is essentially associated with the GABAA receptor-related visual pathway. Furthermore, from our novel approach using observations of goldfish behavior the induced discrete snapshot duration was approximately 573 ms when the fish were under the influence of muscimol.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.65-70
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• 2012

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.55-59
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• 2021

West syndrome (WS) presenting with infantile spasms, developmental delay, and hypsarrhythmia has genetic etiology in some patients. Movement disorders or visual impairment that share genetic underpinnings with infantile spasms can provide diagnostic clues for specific genetic mutations. Mutations of the GRIN1 gene encoding the glutamate receptor inotropic N-methyl-D-aspartate subunit can result in WS with hyperkinetic movements, cortical visual impairment, autistic features, and bilateral polymicrogyria. An 11-month-old boy with WS showed hyperkinetic movements and visual impairment. Brain magnetic resonance imaging and metabolic investigations revealed no abnormalities. Whole-exome sequencing revealed a novel likely pathogenic variant (c.1561_1563del; p.Asn521del) of GRIN1 (NM_007327.3). The proband was treated with vigabatrin and became seizure-free within one week. Notably, the cortical blindness improved within 3 months and the hyperkinetic movements resolved one year after the proband became seizure-free. To the best of our knowledge, this is the first report of GRIN1 encephalopathy in Koreans.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.259-263
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• 1999

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes $5-HT_{2A}$ and ${\alpha}_1$ adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT2 antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.

• Korean Journal of Animal Reproduction
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• v.27 no.4
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• pp.333-338
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• 2003

Transgenic mice containing GH Receptor (GHR) gene fused to metallothionein promoter were analyzed to evaluate effect of GHR expression on growth in vivo. Three founder mice lines contained copies of GHR transgene and transmitted these genes into F$_1$ and F$_2$ progenies. The mRNA expression of transgene was identified using RT-PCR with GHR genes in tissues. To analyze the effects of transgenes on growth performance, body weights of pups were measured at 4, 10 and 14 weeks after birth. The body weight of transgenic mice was higher compared with that of non-transgenic control mice regardless of sex (P<0.05). Body weights between transgenic and non-transgenic mice were increased with aging. Overall, GHR transgenic mice tended to grow about 10 to 15 ％ faster than non-transgenic mice without any pathological defects.

• Journal of Photoscience
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• v.9 no.2
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• pp.17-20
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• 2002

We have cloned a cDNA for an opsin (Boceropsin) from the silkworm larval brain which was suggested to contain the photoperiodic receptor. Its deduced amino acid sequence was composed of 381 amino acids and included amino acid residues highly conserved in insect visual pigments. This opsin belonged to the long wavelength photoreceptor group of insect opsins, and are presumed to be photoperiodic receptor. RT-PCR analysis revealed that Boceropsin mRNA is expressed in the larval brain, but not in the subesophageal (Sg) and thoracic ganglion. Immunohistochemical analyses demonstrated that Boceropsin protein is present bilaterally in some defined cells localized in the brain of the Bombyx larva. Boceropsin was considered not to be involved in the circadian photoreception, because carotenoids are not indispensable for the photoreception and formation of circadian rhythms in the silkworm.