Experimental Neurobiology最新文献

{"title":"Differential Encoding of Trace and Delay Fear Memory in the Entorhinal Cortex.","authors":"Mi-Seon Kong, Namsoo Kim, Kyeong Im Jo, Sung-Phil Kim, June-Seek Choi","doi":"10.5607/en22042","DOIUrl":"10.5607/en22042","url":null,"abstract":"<p><p>Trace fear conditioning is characterized by a stimulus-free trace interval (TI) between the conditioned stimulus (CS) and the unconditioned stimulus (US), which requires an array of brain structures to support the formation and storage of associative memory. The entorhinal cortex (EC) has been proposed to provide essential neural code for resolving temporal discontinuity in conjunction with the hippocampus. However, how the CS and TI are encoded at the neuronal level in the EC is not clear. In Exp. 1, we tested the effect of bilateral pre-training electrolytic lesions of EC on trace vs. delay fear conditioning using rats as subjects. We found that the lesions impaired the acquisition of trace but not delay fear conditioning confirming that EC is a critical brain area for trace fear memory formation. In Exp. 2, single-unit activities from EC were recorded during the pre-training baseline and post-training retention sessions following trace or delay conditioning. The recording results showed that a significant proportion of the EC neurons modulated their firing during TI after the trace conditioning, but not after the delay fear conditioning. Further analysis revealed that the majority of modulated units decreased the firing rate during the TI or the CS. Taken together, these results suggest that EC critically contributes to trace fear conditioning by modulating neuronal activity during the TI to facilitate the association between the CS and US across a temporal gap.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 1","pages":"20-30"},"PeriodicalIF":1.8,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c3/a0/en-32-1-20.PMC10017844.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Policy Analysis for Implementing Neuroethics in Korea's Brain Research Promotion Act.","authors":"Tae-Woo Kang,&nbsp;Tai-Won Oh,&nbsp;Sung-Jin Jeong","doi":"10.5607/en22037","DOIUrl":"https://doi.org/10.5607/en22037","url":null,"abstract":"<p><p>In 1998, Korea implemented the Brain Research Promotion Act (BRPA), a law to revamp the field of neuroscience at the national level. However, despite numerous revisions including the definition and classification of neuroscience and the national plans for the training and education systems, the governance for neuroethics has not been integrated into the Act. The ethical issues raised by neuroscience and neurotechnology remain unchallenged, especially given the focus on the industrial purpose of the technology. In the current study, we analyzed the BRPA revision process by using Kingdon's Multiple Streams Framework to determine the problems faced by the process. We propose a new strategy, including neuroethics governance and a national committee, to promote interdisciplinary neuroscience research and strengthen neuroethics in Korea.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 1","pages":"1-7"},"PeriodicalIF":2.4,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/34/en-32-1-1.PMC10017843.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An XYZ-axis Matrix Approach for the Integration of Neuroscience and Neuroethics.","authors":"Anita S Jwa,&nbsp;Jiwon Shim,&nbsp;Sinu Choi,&nbsp;Juhee Eom,&nbsp;Soojin Kim,&nbsp;Young-Joon Ryu","doi":"10.5607/en22032","DOIUrl":"https://doi.org/10.5607/en22032","url":null,"abstract":"<p><p>The recent, unprecedented advancement in neuroscience has led to new discoveries about the human brain and its function. Yet at the same time, it has spurred novel ethical and regulatory issues, and the field of neuroethics has emerged as an interdisciplinary endeavor to address these issues. Across the globe, extensive efforts have been underway to achieve the integration of neuroscience and Neuroethics, with active engagement not only from academia but also from the government, the public, and industry. However, in some countries, integrating neuroscience and neuroethics has proved to be a particularly challenging task. For example, in South Korea, the government has primarily driven the integration effort, and only a small group of researchers is properly trained for conducting an interdisciplinary evaluation of ethical, legal, social, and cultural implications (ELSCI) of neurotechnology. On the basis of the last few years of experience pursuing a government-funded neuroethics project in South Korea, we developed a new operational framework to provide practical guidance on ELSCI research. This framework consists of the X, Y, and Z axes; the X-axis represents a target neurotechnology, the Y-axis represents different developmental stages of the technology, and the Z-axis represents ELSCI issues that may arise from the development and use of the neurotechnology. Here we also present a step-by-step workflow to apply this matrix framework, from organizing a panel for a target neurotechnology to facilitating stakeholder discussion through public hearings. This framework will enable meaningful integration of neuroscience and neuroethics to promote responsible innovation in neuroscience and neurotechnology.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 1","pages":"8-19"},"PeriodicalIF":2.4,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/dc/en-32-1-8.PMC10017846.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reelin and APP Cooperatively Modulate Dendritic Spine Formation <i>In Vitro</i> and <i>In Vivo</i>.","authors":"Hyun-Ju Lee,&nbsp;Jin-Hee Park,&nbsp;Justin H Trotter,&nbsp;James N Maher,&nbsp;Kathleen E Keenoy,&nbsp;You Mi Jang,&nbsp;Youngeun Lee,&nbsp;Jae-Ick Kim,&nbsp;Edwin J Weeber,&nbsp;Hyang-Sook Hoe","doi":"10.5607/en22044","DOIUrl":"https://doi.org/10.5607/en22044","url":null,"abstract":"<p><p>Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer's disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, <i>in vitro</i>. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or <i>in vivo</i> in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 1","pages":"42-55"},"PeriodicalIF":2.4,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/da/en-32-1-42.PMC10017845.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9483679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine Receptor Supports the Potentiation of Intrinsic Excitability and Synaptic LTD in Temporoammonic-CA1 Synapse.","authors":"Hye-Hyun Kim,&nbsp;Suk-Ho Lee,&nbsp;Won-Kyung Ho,&nbsp;Kisang Eom","doi":"10.5607/en22028","DOIUrl":"https://doi.org/10.5607/en22028","url":null,"abstract":"<p><p>Dopaminergic projection to the hippocampus from the ventral tegmental area or locus ceruleus has been considered to play an essential role in the acquisition of novel information. Hence, the dopaminergic modulation of synaptic plasticity in the hippocampus has been widely studied. We examined how the D1 and D2 receptors influenced the mGluR5-mediated synaptic plasticity of the temporoammonic-CA1 synapses and showed that the dopaminergic modulation of the temporoammonic-CA1 synapses was expressed in various ways. Our findings suggest that the dopaminergic system in the hippocampal CA1 region regulates the long-term synaptic plasticity and processing of the novel information.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"361-375"},"PeriodicalIF":2.4,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/2d/en-31-6-361.PMC9841748.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the Effect of Placental Extract on the Regeneration of Crush Injured Facial Nerve.","authors":"Gyeong Min Lim,&nbsp;Gwang-Won Cho,&nbsp;Chitra Devi Ganesan,&nbsp;Ji Hyun Choi,&nbsp;Mary Jasmin Ang,&nbsp;Changjong Moon,&nbsp;Chul Ho Jang","doi":"10.5607/en22006","DOIUrl":"https://doi.org/10.5607/en22006","url":null,"abstract":"<p><p>There is a scarcity of experimental studies on peripheral nerve regeneration using placental extract (PE). This study aimed to investigate the effects of topical PE application on recovery after crush injury to the rat facial nerve using functional, electrophysiological, and morphological evaluations. The viability of the RSC96 Schwann cells treated with PE (0.5~4 mg/ml) increased significantly. Immunoblot test revealed that PE application enhanced the migration of RSC96 cells. Quantitative polymerase chain reaction demonstrated that PE increased the expression of neurotropic genes. The recovery from vibrissa fibrillation in the PE-treated group was superior to that in the control group. The threshold of action potential was also significantly lower in the PE group. Histopathological examination showed that crushed facial nerves treated with PE exhibited larger axons. The surrounding myelin sheaths were more distinct and thicker in the PE-treated group. Hence, PE may be considered a topical therapeutic agent for treating traumatic facial nerve paralysis.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"419-430"},"PeriodicalIF":2.4,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/a2/en-31-6-419.PMC9841744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors.","authors":"Myungmo An,&nbsp;Hyun-Kyung Kim,&nbsp;Hoyong Park,&nbsp;Kyunghoe Kim,&nbsp;Gyuryang Heo,&nbsp;Han-Eol Park,&nbsp;ChiHye Chung,&nbsp;Sung-Yon Kim","doi":"10.5607/en22024","DOIUrl":"https://doi.org/10.5607/en22024","url":null,"abstract":"<p><p>The lateral septum (LS) is a forebrain structure that has been implicated in a wide range of behavioral and physiological responses to stress. However, the specific populations of neurons in the LS that mediate stress responses remain incompletely understood. Here, we show that neurons in the dorsal lateral septum (LSd) that express the somatostatin gene (hereafter, LSd^<i>Sst</i> neurons) are activated by diverse stressors. Retrograde tracing from LSd^<i>Sst</i> neurons revealed that these neurons are directly innervated by neurons in the locus coeruleus (LC), the primary source of norepinephrine well-known to mediate diverse stress-related functions in the brain. Consistently, we found that norepinephrine increased excitatory synaptic transmission onto LSd^<i>Sst</i> neurons, suggesting the functional connectivity between LSd^<i>Sst</i> neurons and LC noradrenergic neurons. However, optogenetic stimulation of LSd^<i>Sst</i> neurons did not affect stress-related behaviors or autonomic functions, likely owing to the functional heterogeneity within this population. Together, our findings show that LSd^<i>Sst</i> neurons are activated by diverse stressors and suggest that norepinephrine released from the LC may modulate the activity of LSd^<i>Sst</i> neurons under stressful circumstances.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"376-389"},"PeriodicalIF":2.4,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/97/39/en-31-6-376.PMC9841747.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9186816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional Comparison of Imaging Biomarkers in the Striatum between Early- and Late-onset Alzheimer's Disease.","authors":"Ji Eun Kim, Dong-Kyun Lee, Ji Hye Hwang, Chan-Mi Kim, Yeji Kim, Jae-Hong Lee, Jong-Min Lee, Jee Hoon Roh","doi":"10.5607/en22022","DOIUrl":"10.5607/en22022","url":null,"abstract":"<p><p>Striatal changes in the pathogenesis of Alzheimer's disease (AD) is not fully understood yet. We compared structural and functional image differences in the striatum between patients with early onset AD (EOAD) and late onset AD (LOAD) to investigate whether EOAD harbors autosomal dominant AD like imaging findings. The clinical, neuropsychological and neuroimaging biomarkers of 77 probable AD patients and 107 elderly subjects with normal cognition (NC) from the Alzheimer's Disease Neuroimaging Initiative (ADNI)-2 dataset were analyzed. Enrolled each subject completed a 3-Tesla MRI, baseline 18F-FDG-PET, and baseline 18F-AV-45 (Florbetapir) amyloid PET studies. AD patients were divided into two groups based on the onset age of clinical symptoms (EOAD <65 yrs; LOAD ≥65 yrs). A standardized uptake value ratio of the striatum and subcortical structures was obtained from both amyloid and FDG-PET scans. Structural MR imaging analysis was conducted using a parametric boundary description protocol, SPHARM-PDM. Of the 77 AD patients, 18 were EOAD and 59 were LOAD. Except for age of symptom onset, there were no statistically significant differences between the groups in demographics and detailed neuropsychological test results. 18F-AV-45 amyloid PET showed marked β-amyloid accumulation in the bilateral caudate nucleus and left pallidum in the EOAD group. Intriguingly, the caudate nucleus and putamen showed maintained glucose metabolism in the EOAD group compared to the LOAD group. Our image findings in the striatum of EOAD patients suggest that sporadic EOAD may share some pathophysiological changes noted in autosomal dominant AD.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"401-408"},"PeriodicalIF":1.8,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/18/en-31-6-401.PMC9841745.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Claustral MeCP2 Regulates Methamphetamine-induced Conditioned Place Preference in Cynomolgus Monkey.","authors":"Jinhee Bae,&nbsp;Sujin Ahn,&nbsp;Doo-Wan Cho,&nbsp;Hyung-Sun Kim,&nbsp;Su-Cheol Han,&nbsp;Heh-In Im","doi":"10.5607/en22034","DOIUrl":"https://doi.org/10.5607/en22034","url":null,"abstract":"<p><p>The claustrum, a brain nucleus located between the cortex and the striatum, has recently been highlighted in drug-related reward processing. Methyl CpG-binding protein-2 (MeCP2) is a transcriptional regulator that represses or activates the expression of the target gene and has been known to have an important role in the regulation of drug addiction in the dopaminergic reward system. The claustrum is an important region for regulating reward processing where most neurons receive dopamine input; additionally, in this region, MeCP2 is also abundantly expressed. Therefore, here, we hypothesized that MeCP2 would be involved in drug addiction control in the Claustrum as well and investigated how claustral MeCP2 regulates drug addiction. To better understand the function of human claustral MeCP2, we established a non-human primate model of methamphetamine (METH) - induced conditioned place preference (CPP). After a habituation of two days and conditioning of ten days, the CPP test was conducted for three days. Interestingly, we confirmed that virus-mediated overexpression of MECP2 in the claustrum showed a significant reduction of METH-induced CPP in the three consecutive days during the testing period. Moreover, they showed a decrease in visit scores (frequency for visit) for the METH-paired room compared to the control group although the scores were statistically marginal. Taken together, we suggest that the claustrum is an important brain region associated with drug addiction, in which MeCP2 may function as a mediator in regulating the response to addictive drugs.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"390-400"},"PeriodicalIF":2.4,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/b0/en-31-6-390.PMC9841746.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9186815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"XperCT-guided Intra-cisterna Magna Injection of Streptozotocin for Establishing an Alzheimer's Disease Model Using the Cynomolgus Monkey (<i>Macaca fascicularis</i>).","authors":"Junghyung Park,&nbsp;Jinyoung Won,&nbsp;Chang-Yeop Jeon,&nbsp;Kyung Seob Lim,&nbsp;Won Seok Choi,&nbsp;Sung-Hyun Park,&nbsp;Jincheol Seo,&nbsp;Jiyeon Cho,&nbsp;Jung Bae Seong,&nbsp;Hyeon-Gu Yeo,&nbsp;Keonwoo Kim,&nbsp;Yu Gyeong Kim,&nbsp;Minji Kim,&nbsp;Kyung Sik Yi,&nbsp;Youngjeon Lee","doi":"10.5607/en22027","DOIUrl":"https://doi.org/10.5607/en22027","url":null,"abstract":"<p><p>Till date, researchers have been developing animal models of Alzheimer's disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ). However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM. Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"31 6","pages":"409-418"},"PeriodicalIF":2.4,"publicationDate":"2022-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/10/7b/en-31-6-409.PMC9841743.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9171640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}