• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.1-8
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• 2016

Damage in the periphery or spinal cord induces maladaptive plastic changes along the somatosensory nervous system from the periphery to the cortex, often leading to chronic pain. Although the role of neural circuit remodeling and structural synaptic plasticity in the 'pain matrix' cortices in chronic pain has been thought as a secondary epiphenomenon to altered nociceptive signaling in the spinal cord, progress in whole brain imaging studies on human patients and animal models has suggested a possibility that plastic changes in cortical neural circuits may actively contribute to chronic pain symptoms. Furthermore, recent development in two-photon microscopy and fluorescence labeling techniques have enabled us to longitudinally trace the structural and functional changes in local circuits, single neurons and even individual synapses in the brain of living animals. These technical advances has started to reveal that cortical structural remodeling following tissue or nerve damage could rapidly occur within days, which are temporally correlated with functional plasticity of cortical circuits as well as the development and maintenance of chronic pain behavior, thereby modifying the previous concept that it takes much longer periods (e.g. months or years). In this review, we discuss the relation of neural circuit plasticity in the 'pain matrix' cortices, such as the anterior cingulate cortex, prefrontal cortex and primary somatosensory cortex, with chronic pain. We also introduce how to apply long-term in vivo two-photon imaging approaches for the study of pathophysiological mechanisms of chronic pain.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.69-75
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• 2022

Chronic pain is induced by tissue or nerve damage and is accompanied by pain hypersensitivity (i.e., allodynia and hyperalgesia). Previous studies using in vivo two-photon microscopy have shown functional and structural changes in the primary somatosensory (S1) cortex at the cellular and synaptic levels in inflammatory and neuropathic chronic pain. Furthermore, alterations in local cortical circuits were revealed during the development of chronic pain. In this review, we summarize recent findings regarding functional and structural plastic changes of the S1 cortex and alteration of the S1 inhibitory network in chronic pain. Finally, we discuss potential neuromodulators driving modified cortical circuits and suggest further studies to understand the cortical mechanisms that induce pain hypersensitivity.

• Korean Journal of Biological Psychiatry
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• v.18 no.1
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• pp.15-24
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• 2011

Mood disorder is unlikely to be a disease of a single brain region or a neurotransmitter system. Rather, it is now generally viewed as a multidimensional disorder that affects many neural pathways. Growing neuroimaging evidence suggests the anterior cingulate-pallidostriatal-thalamic-amygdala circuit as a putative cortico-limbic mood regulating circuit that may be dysfunctional in mood disorders. Brain-imaging techniques have shown increased activation of mood-generating limbic areas and decreased activation of cortical areas in major depressive disorder(MDD). Furthermore, the combination of functional abnormalities in limbic subcortical neural regions implicated in emotion processing together with functional abnormalities of prefrontal cortical neural regions probably result in the emotional lability and impaired ability to regulate emotion in bipolar disorder. Here we review the biological correlates of MDD and bipolar disorder as evidenced by neuroimaging paradigms, and interpret these data from the perspective of endophenotype. Despite possible limitations, we believe that the integration of neuroimaging research findings will significantly advance our understanding of affective neuroscience and provide novel insights into mood disorders.

• Korean Journal of Biological Psychiatry
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• v.24 no.4
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• pp.225-234
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• 2017

Objectives Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. Methods Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. Results The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. Conclusions Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.231-241
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• 2001

The mammalian cortical collecting duct (CCD) plays a major role in regulating renal NaCl reabsorption, which is important in $Na^+$ and $Cl^-$ homeostasis. The M-1 cell line, derived from the mouse cortical collecting duct, has been used as a mammalian model of the study on the electrolytes transport in CCD. M-1 cells were grown on collagen-coated permeable support and short circuit current $(I_{sc})$ was measured. M-1 cells developed amiloride-sensitive current $5{\sim}7$ days after seeding. Apical and basolateral addition of ATP induced increase in $I_{sc}$ in M-1 cells, which was partly retained in $Na^+-free$ or $Cl^--free$ solution, indicating that ATP increased $Na^+$ absorption and $Cl^-$ secretion in M-1 cells. $Cl^-$ secretion was mediated by the activation of apical cystic fibrosis transmembrane regulator (CFTR) chloride channels and $Ca^{2+}-activated$ chloride channels, but $Na^+$ absorption was not mediated by activation of epithelal sodium channel (ENaC). ATP increased cAMP content in M-1 cells. The RT-PCR analysis demonstrated that M-1 cells express $P2Y_2,\;P2X_3\;and\;P2Y_4$ receptors. These results showed that ATP regulates $Na^+$ and $Cl^-$ transports via multiple P2 purinoceptors on the apical and basolateral membranes in M-1 cells.

• Journal of Yeungnam Medical Science
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• v.17 no.2
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• pp.108-122
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• 2000

Background: Models of attention deficit hyperactivity disorder(ADHD) that have proposed a hypodopaminergic state resulting in hypofunction of the prefrontal circuitry have assumed a unitary dopamine system, which largely ignores the distinct functional differences between mesocortical dopamine system and nigrostriatal dopamine system. Purpose: The author's goal was to develop a pathophysiological model for ADHD with greater explanotory power than dopaminergic hypofunction hypothesis in prefronal circuitry. Material and Methods: Published clinical findings on ADHD were integrated with data from genetic, pharmacological, neuroimaging studies in human and animals. Results: Molecular genetic studies suggest that three genes may increase the susceptibility to ADHD. The three candidate genes associated with ADHD are each involved in dopaminergic function, and this consistent with the neurobiologic studies implicating catecholamines in the etiology of ADHD. Pharmacological data also provide compelling support for dopamine and noradrenergic hypothesis of ADHD. Neuroimaging studies lend substantial support for the hypothesis that right-sided abnormalities of prefrontal-basal ganglia circuit would be found in ADHD. Conclusions: The present hypothesis takes advantage of the major differences between the two pertinent dopamine systems. Mesocortical dopamine system, which largely lacks inhibitory autoreceptors, is ideally positioned to regulate cortical inputs, thus improving the signal-to-noise ratio for biologically valued signals. In this circuit, therapeutic doses of stimulants are hypothesized to increase postsynaptic dopamine effects and enhance executive functions. By contrast, symptoms of hyperactivity/impulsivity in ADHD are hypothesized to be associated with relative overactivity of nigrostriatal circuit. This nigrostriatal circuit is tightly regulated by inhibitory autoreceptoors as well as by long distance feedback from the cortex, and slow diffusion of therapeutic doses of stimulant via oral administration is hypothesized to produce a net inhibition of dopaminergic neurotransmission and improves hyperactivity.

• Sleep Medicine and Psychophysiology
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• v.28 no.2
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• pp.43-52
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• 2021

Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep disorder characterized by sensorimotor symptoms such as unpleasant sensations before sleep, akathisia, and periodic limb movements during sleep. It is also closely related to hyperarousal and is often accompanied by insomnia. Although the mechanism is not clear, the understanding of etiology and pathophysiology has greatly expanded through recent advances in genetic and neurobiological research. The most important pathophysiology of RLS/WED is brain iron deficiency. Such iron deficiency in the brain is caused by complex interactions between several genetic factors and various environmental factors, including comorbidities. Iron deficiency in the brain results in dysfunction of several neurotransmitters. A decrease in adenosine activity appears first, followed by an increase in the activity of glutamate and dopamine. A decrease in adenosine activity and an increase in glutamate activity stimulate the brain arousal system, resulting in hyperarousal. In addition, overproduction of dopamine and glutamate leads to dysfunction of the cortical-striatal-thalamic circuit, resulting in symptoms such as akathisia and periodic limb movements during sleep.

• Science of Emotion and Sensibility
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• v.20 no.4
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• pp.113-126
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• 2017

The purpose of the study was to find grey matter (GM) and white matter (WM) volume reduction in the brain reward system among patients with alcohol dependency. This study investigated regional GM and WM in chronic alcoholic patients, focusing primarily on the reward system, including principal components of the mesocorticolimbic reward circuit as well as cortical areas with modulating and oversight functions. Sixteen abstinent long-term chronic alcoholic men and demographically matched 16 healthy control men participated in the study. Morphometric analysis was performed on magnetic resonance brain scans using voxel-based morphometry (VBM)-diffeomorphic Anatomical Registration through Exponentiated Liealgebra (DARTEL). We derived GM and WM volumes from total brain and cortical and subcortical reward-related structures. Morphometric analyses that revealed the total volume of GM and WM was reduced and cerebrospinal fluid (CSF) was increased in the alcohol group compared to control group. The pronounced volume reduction in the reward system was observed in the GM and WM of the nucleus accumbens (NAc), GM of the amygdala, GM and WM of the hippocampus, WM of the thalamus, GM and WM of the insula, GM of the dorsolateral prefrontal cortex (DLPFC), GM of the orbitofrontal cortex (OFC), GM of the cingulate cortex (CC), GM and WM of the parahippocampal gyrus in the alcohol group. We identified volume reductions in WM as well as GM of reward system in the patients with alcohol dependency. These structural deficits in the reward system elucidate underlying impairment in the emotional and cognitive processing in alcoholism.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.57-71
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• 2004

Objective : Physiological evidence regarding acupuncture's effect in human patients is not yet well established, despite considerable evidence for its therapeutic efficacy. Besides target or disease specificity of acupuncture, acupuncture analgesia (AA) appears to be another large subclass that poses many questions, such as whether there is point specificity with respect to which acupoint is most effective for a particular condition. Methods : We observed brain activation with functional magnetic resonance imaging (fMRI) using a set of stimuli that consist of pain, pain following Meridian acupuncture, and pain following Sham acupuncture. Results : Among the new observations, the most interesting fact is that data sets of both Meridian acupuncture and Sham acupuncture show decreased activation of the same brain areas related to the pain processing signals. Present functional MRI study demonstrate two important biological observations that could elucidate AA mechanism in human participants: the effects of acupuncture occur through mediation of the higher brain areas. Sham acupuncture stimulation appears to be almost as effective as traditional Meridian acupoint stimulation, suggesting that acupuncture is not entirely point specific. Decreased activation in the limbic paleo cortical areas appears to be the probable neurological manifestation of AA and strongly implies that acupuncture stimulation inhibits the transmission of ascending pain signals to the higher cortical areas by the previously known descending pain inhibitory circuit. Conclusion : We, therefore, a hypothesized that this pain inhibitory circuit is initiated and mediated via the broad sense Hypothalamus Pituitary Adrenal (BS HPA) axis in conjunction to the "sensory stimulation."

• Molecules and Cells
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• v.45 no.2
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• pp.84-92
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• 2022

To understand the microcircuitry of the brain, the anatomical and functional connectivity among neurons must be resolved. One of the technical hurdles to achieving this goal is that the anatomical connections, or synapses, are often smaller than the diffraction limit of light and thus are difficult to resolve by conventional microscopy, while the microcircuitry of the brain is on the scale of 1 mm or larger. To date, the gold standard method for microcircuit reconstruction has been electron microscopy (EM). However, despite its rapid development, EM has clear shortcomings as a method for microcircuit reconstruction. The greatest weakness of this method is arguably its incompatibility with functional and molecular analysis. Fluorescence microscopy, on the other hand, is readily compatible with numerous physiological and molecular analyses. We believe that recent advances in various fluorescence microscopy techniques offer a new possibility for reliable synapse detection in large volumes of neural circuits. In this minireview, we summarize recent advances in fluorescence-based microcircuit reconstruction. In the same vein as these studies, we introduce our recent efforts to analyze the long-range connectivity among brain areas and the subcellular distribution of synapses of interest in relatively large volumes of cortical tissue with array tomography and superresolution microscopy.