• Animal cells and systems
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• 제6권2호
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• pp.159-165
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• 2002

Projections from the prefrontal cortex to subdivisions of the dorsal raphe nucleus were investigated in the rat using retrograde and anterograde tracing methods. A retrograde tracer, gold-conjugated horseradish peroxidase (WGA-apo-HRP-gold), was injected into each subdivision of the dorsal raphe including lateral wing, dorsomedial, and ventromedial areas. The majority of retrogradely labeled cells were located in the prelimbic, infralim-bic, and dorsal peduncular areas of the medial prefrontal cortex. A few cells were also identified in the cingulate, various regions of the orbital, and agranular insular cortices. Secondly, an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), was injected into the medial prefrontal cortex involving the prelimbic or infralimbic areas. Axonal fibers with varicosities were identified in all subdivisions of the DR including the lateral wing, dorsomedial, and ventromedial areas. Projections were bilateral, with ipsilateral predominance. Axonal fibers were observed at the lateral border of medial longitudinal fasciculus or in the interfascicular region at the midline. The present findings demonstrate that both the midline and lateral wing regions of the dorsal raphe nucleus receive excitatory input from cognitive and emotional centers of the cerebral cortex.

• Animal cells and systems
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• 제7권1호
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• pp.49-55
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• 2003

The fiber projection from the prefrontal cortex to the locus coeruleus (LC) in the periventricular region was analyzed in rat using anterograde and retrograde tracing methods. Following injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), into prelimbic and infralimbic regions of the medial prefrontal cortex, labeled axonal fibers with varicosities were observed bilaterally within the LC, with ipsilateral predominance. Terminal labeling was also observed in the region medial to the nucleus at rostral to middle levels of the LC, whereas axonal labeling in the caudal LC was minimal. Anterogradely-labeled axonal fibers were not found in the subcoerulear region. A retrograde tracer, gold-conjugated and inactivated wheatgerm-agglutinin horseradish-peroxidase (WGA-apo-HRP-gold), was injected into several rostro-caudal levels of the LC. Majority of retrogradely-labeled cells were observed in the prelimbic or infralimbic regions of the medial prefrontal cortex when the injections were made into rostral to middle levels of the LC. Only a few cells were observed in cingulate, dorsal peduncular, orbital, or insular cortices. The present findings suggest that the nucleus LC receives restricted, excitatory inputs from cognitive, emotional, and autonomic centers of the cerebral cortex and might secondarily have influences on widespread brain regions via its diversified monoaminergic innervation.

• Journal of Ginseng Research
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• 제42권3호
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• pp.298-303
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• 2018

Background: Panax ginseng is one of the most commonly used medicinal herbs worldwide for a variety of therapeutic properties including neurocognitive effects. Ginsenoside Rg1 is one of the most abundant active chemical constituents of this herb with known neuroprotective, anxiolytic, and cognition improving effects. Methods: We investigated the effects of Rg1 on the medial prefrontal cortex (mPFC), a key brain region involved in cognition, information processing, working memory, and decision making. In this study, the effects of systemic administration of Rg1 (1 mg/kg, 3 mg/kg, or 10 mg/kg) on (1) spontaneous firing of the medial prefrontal cortical neurons and (2) long-term potentiation (LTP) in the hippocampal-medial prefrontal cortical (HP-mPFC) pathway were investigated in male Sprague-Dawley rats. Results: The spontaneous neuronal activity of approximately 50% the recorded pyramidal cells in the mPFC was suppressed by Rg1. In addition, Rg1 attenuated LTP in the HP-mPFC pathway. These effects were not dose-dependent. Conclusion: This report suggests that acute treatment of Rg1 impairs LTP in the HP-mPFC pathway, perhaps by suppressing the firing of a subset of mPFC neurons that may contribute to the neurocognitive effects of Rg1.

• The Journal of Korean Physical Therapy
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• 제29권3호
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• pp.109-114
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• 2017

Purpose: The ascending reticular activating system (ARAS) is responsible for regulation of consciousness. In this study, using diffusion tensor imaging (DTI), we attempted to reconstruct the thalamocortical projections between the intralaminar thalamic nuclei and the frontoparietal cortex in normal subjects. Methods: DTI data were acquired in 24 healthy subjects and eight kinds of thalamocortical projections were reconstructed: the seed region of interest (ROI) - the intralaminar thalamic nuclei and the eight target ROIs - the medial prefrontal cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, premotor cortex, primary motor cortex, primary somatosensory cortex, and posterior parietal cortex. Results: The eight thalamocortical projections were reconstructed in each hemisphere and the pathways were visualized: projections to the prefrontal cortex ascended through the anterior limb and genu of the internal capsule and anterior corona radiata. Projections to the premotor cortex passed through the genu and posterior limb of the internal capsule and middle corona radiata; in contrast, projections to the primary motor cortex, primary somatosensory cortex, and posterior parietal cortex ascended through the posterior limb of the internal capsule. No significant difference in fractional anisotropy, mean diffusivity, and fiber volume of all reconstructed thalamocortical projections was observed between the right and left hemispheres (p>0.05). Conclusion: We reconstructed the thalamocortical projections between the intralaminar thalamic nuclei and the frontoparietal cortex in normal subjects. We believe that our findings would be useful to clinicians involved in the care of patients with impaired consciousness and for researchers in studies of the ARAS.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.230-239
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• 2020

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

• The Korean Journal of Pain
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• 제35권4호
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• pp.413-422
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• 2022

Background: The neocortex, including the medial prefrontal cortex (mPFC), contains many neurons expressing nitric oxide synthase (NOS). In addition, increasing evidence shows that the nitric oxide (NO) and opioid systems interact in the brain. However, there have been no studies on the interaction of the opioid and NO systems in the mPFC. The objective of this study was to investigate the effects of administrating L-arginine (L-Arg, a precursor of NO) and N(gamma)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NOS) into the mPFC for neuropathic pain in rats. Also, we used selective opioid receptor antagonists to clarify the possible participation of the opioid mechanism. Methods: Complete transection of the peroneal and tibial branches of the sciatic nerve was applied to induce neuropathic pain, and seven days later, the mPFC was cannulated bilaterally. The paw withdrawal threshold fifty percent (50% PWT) was recorded on the 14th day. Results: Microinjection of L-Arg (2.87, 11.5 and 45.92 nmol per 0.25 µL) increased 50% PWT. L-NAME (17.15 nmol per 0.25 µL) and naloxonazine (an antagonist of mu opioid receptors, 1.54 nmol per 0.25 µL) inhibited anti-allodynia induced by L-Arg (45.92 nmol per 0.25 µL). Naltrindole (a delta opioid receptor antagonist, 2.45 nmol per 0.25 µL) and nor-binaltorphimine (a kappa opioid receptor antagonist, 1.36 nmol per 0.25 µL) were unable to prevent L-Arg (45.92 nmol per 0.25 µL)-induced antiallodynia. Conclusions: Our results indicate that the NO system in the mPFC regulates neuropathic pain. Mu opioid receptors of this area might participate in pain relief caused by L-Arg.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.449-460
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• 2018

Objective: Prior functional magnetic resonance imaging (fMRI) work has revealed that children/adolescents with disruptive behavior disorders (DBDs) show dysfunctional reward/non-reward processing of non-social reinforcements in the context of instrumental learning tasks. Neural responsiveness to social reinforcements during instrumental learning, despite the importance of this for socialization, has not yet been previously investigated. Methods: Twenty-nine healthy children/adolescents and 19 children/adolescents with DBDs performed the fMRI social/non-social reinforcement learning task. Participants responded to random fractal image stimuli and received social and non-social rewards/non-rewards according to their accuracy. Results: Children/adolescents with DBDs showed significantly reduced responses within the caudate and posterior cingulate cortex (PCC) to non-social (financial) rewards and social non-rewards (the distress of others). Connectivity analyses revealed that children/adolescents with DBDs have decreased positive functional connectivity between the ventral striatum (VST) and the ventromedial prefrontal cortex (vmPFC) seeds and the lateral frontal cortex in response to reward relative to non-reward, irrespective of its sociality. In addition, they showed decreased positive connectivity between the vmPFC seed and the amygdala in response to non-reward relative to reward. Conclusion: These data indicate compromised reinforcement processing of both non-social rewards and social non-rewards in children/adolescents with DBDs within core regions for instrumental learning and reinforcement-based decision-making (caudate and PCC). In addition, children/adolescents with DBDs show dysfunctional interactions between the VST, vmPFC, and lateral frontal cortex in response to rewarded instrumental actions potentially reflecting disruptions in attention to rewarded stimuli.

• 대한감각통합치료학회지
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• 제14권1호
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• pp.50-59
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• 2016

목적 : 본 연구에서는 감정조절에 대한 신경학적 메커니즘을 이해하고, 감정조절과 감각처리의 연관성에 대해 알아보고자 한다. 본론 : 신경학적으로 감정조절은 주로 둘레계의 구조물에 의해 처리되고 특히, 편도의 바닥-바깥쪽 그룹이 주요한 역할을 한다. 바닥-바깥쪽 그룹은 감각의 중계소인 시상과 직 간접적으로 연결되어 감각 정보에 대한 처리를 함께 한다. 이 감각 정보는 눈-안쪽 앞 이마엽과 연결되어 감각처리 및 감정과 관련된 복잡한 행동을 하게 한다. 시상, 편도, 눈-안쪽 앞 이마엽의 연결 회로로 인해 부적절한 감각처리는 감정조절과 행동에 어려움을 발생시킬 수 있다. 자폐스펙트럼장애와 주의력결핍과잉행동장애 아동에서 편도 및 앞 이마엽의 비정상적인 처리에 대한 신경학적 연구가 보고되고 있다. 결론 : 자폐스펙트럼장애와 주의력결핍과잉행동장애 아동은 신경계의 상태가 다르고 이는 감각처리와 감정조절, 행동에서 다양한 양상을 나타낸다. 치료사는 아동의 행동에 영향을 미치는 감각처리와 감정조절에 대한 신경학적 메커니즘을 이해하고, 치료적 적용을 할 필요가 있다.

• 대한한의학방제학회지
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• 제28권1호
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• pp.53-62
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• 2020

Objective : This study is accomplished in order to investigate the effect of banggibongnyeongtang on the immunohistological change in LPS-induced depression rats to confirm the histological result of the previous behavioral and biochemical effect. Methods : LPS 5 ㎍ was injected to lateral ventricle and experimental groups were administered BBT intraperitoneally. The concentration of 5-HT in the Medial Prefrontal Cortex, Striatum, Hippocampus, Amygdala was measured by ELISA. IL-1β, TNF-α mRNA and BDNF mRNA expression in the hippocampus was examined by RT-PCR. Result : BBT enhanced 5-HT concentration at all part of brain but no significantly difference at medial prefrontal cortex and striatum. LPS+BBT400 group increased 5-HT concentration significantly than LPS group at hippocampus and amygdala (p<0.05). BBT decreased IL-1β mRNA expression dose dependently but only with significantly decrease in LPS+BBT400 group than LPS group's in Hippocampus (p<0.05). But BBT did not decrease TNF-α mRNA expression significantly in Hippocampus. BBT increased the expression of BDNF mRNA at hippocampus and LPS+BBT400 group significantly increased comparing with LPS group does (p<0.05). Conclusion : It is postulated that the anti-depressant effect of BBT can be validated through the anti-inflammatory effect, 5-HT concentration increase, and the neuro-protective effect mediated by BDNF by combining the results of the previous report about the behavioral and biochemical effect.

• Journal of Ginseng Research
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• 제48권5호
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• pp.481-493
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• 2024

Background: Post-weaning social isolation (SI) reduces sociability, gene expressions including myelin genes in the medial prefrontal cortex (mPFC), and alters microbiome compositions in rodent models. Korean Red Ginseng (KRG) and its major ginsenoside Rb1 have been reported to affect myelin formation and gut metabolites. However, their effects under post-weaning SI have not been investigated. This study investigated the effects of KRG and Rb1 on sociability, gene expressions in the mPFC, and gut metabolites under post-weaning SI. Methods: C57BL/6J mice were administered with water or KRG (150, 400 mg/kg) or Rb1 (0.1 mg/kg) under SI or regular environment (RE) for 2 weeks during the post-weaning period (P21-P35). After this period, mice underwent a sociability test, and then brains and ceca were collected for qPCR/immunohistochemistry and nontargeted metabolomics, respectively. Results: SI reduced sociability compared to RE; however, KRG (400 mg/kg) and Rb1 significantly restored sociability under SI. In the mPFC, expressions of genes related to myelin, neurotransmitter, and oxidative stress were significantly reduced in mice under SI compared to RE conditions. Under SI, KRG and Rb1 recovered the altered expressions of several genes in the mPFC. In gut metabolomics, 313 metabolites were identified as significant among 3027 detected metabolites. Among the significantly changed metabolites in SI, some were recovered by KRG or Rb1, including metabolites related to stress axis, inflammation, and DNA damage. Conclusion: Altered sociability, gene expression levels in the mPFC, and gut metabolites induced by two weeks of post-weaning SI were at least partially recovered by KRG and Rb1.