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Causal Inference on Pathophysiological Mediators in Psychiatry. 精神病学病理生理介质的因果推论。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-03-08 DOI: 10.1101/sqb.2018.83.037655
Ho Namkung, Brian J Lee, Akira Sawa
{"title":"Causal Inference on Pathophysiological Mediators in Psychiatry.","authors":"Ho Namkung,&nbsp;Brian J Lee,&nbsp;Akira Sawa","doi":"10.1101/sqb.2018.83.037655","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037655","url":null,"abstract":"<p><p>Supported by technological advances and collaborative efforts, psychiatric genetics has provided robust genetic findings in the past decade, particularly through genome-wide association studies (GWASs). However, translating these genetic findings into biological mechanisms and new therapies has been enormously challenging because of the complexity of their interpretation. Furthermore, the heterogeneity among patients with the same diagnosis, such as schizophrenia or major depressive disorder, challenges the biological validity of existing categorical approaches in clinical nosology, which is further complicated by the pleiotropic nature of many genetic variants across multiple disorders. Therefore, in the post-GWAS era, the greatest challenge lies in integrating such enriched genetic information with functional dimensions of neurobiological measures and observable behaviors. In this integration, the causal inference from genotypes to phenotypes through intermediate biological processes is of particular importance. In this review, we aim to construct an intellectual framework in which we may obtain causal, mechanistic insights into how multifactorial etiologies-in particular, many genetic variants-affect downstream biological pathways that lead to dimensions of psychiatric relevance.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"17-23"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37038586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
A Conversation with Scott Small. 与斯科特·斯莫尔的对话。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-02-25 DOI: 10.1101/sqb.2018.83.037689
{"title":"A Conversation with Scott Small.","authors":"","doi":"10.1101/sqb.2018.83.037689","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037689","url":null,"abstract":"Dr. Small: Well, the questions really were about Alzheimer’s and aging. We’ve now expanded to include other disorders, but they’re really organized around the hippocampus and that reflected, in many ways, my background. I trained in part with Eric Kandel, verymuch interested in cell biology. But then in medical school residency that was layered over with clinical questions and it seemed like a good way to start posing mechanistic questions.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"277-279"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37173106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Brain Circuitry for Arousal from Apnea. 从呼吸暂停唤醒的大脑回路。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-04-23 DOI: 10.1101/sqb.2018.83.038125
Clifford B Saper, Satvinder Kaur
{"title":"Brain Circuitry for Arousal from Apnea.","authors":"Clifford B Saper,&nbsp;Satvinder Kaur","doi":"10.1101/sqb.2018.83.038125","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.038125","url":null,"abstract":"<p><p>We wanted to understand the brain circuitry that awakens the individual when there is elevated CO<sub>2</sub> or low O<sub>2</sub> (e.g., during sleep apnea or asphyxia). The sensory signals for high CO<sub>2</sub> and low O<sub>2</sub> all converge on the parabrachial nucleus (PB) of the pons, which contains neurons that project to the forebrain. So, we first deleted the vesicular glutamate transporter 2, necessary to load glutamate into synaptic vesicles, from neurons in the PB, and showed that this prevents awakening to high CO<sub>2</sub> or low O<sub>2</sub> We then showed that PB neurons that express calcitonin gene-related peptide (CGRP) show cFos staining during high CO<sub>2</sub> Using CGRP-Cre-ER mice, we expressed the inhibitory opsin archaerhodopsin just in the PB<sup>CGRP</sup> neurons. Photoinhibition of the PB<sup>CGRP</sup> neurons effectively prevented awakening to high CO<sub>2</sub>, as did photoinhibition of their terminals in the basal forebrain, amygdala, and lateral hypothalamus. The PB<sup>CGRP</sup> neurons are a key mediator of the wakening response to apnea.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"63-69"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.038125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37341821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Challenges and Opportunities in Psychiatric Neuroscience. 精神神经科学的挑战与机遇。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-03-19 DOI: 10.1101/sqb.2018.83.037523
Joshua A Gordon, Julie A Frost Bellgowan, Collene Lawhorn, Rachel B Scheinert
{"title":"Challenges and Opportunities in Psychiatric Neuroscience.","authors":"Joshua A Gordon,&nbsp;Julie A Frost Bellgowan,&nbsp;Collene Lawhorn,&nbsp;Rachel B Scheinert","doi":"10.1101/sqb.2018.83.037523","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037523","url":null,"abstract":"<p><p>Psychiatry faces a number of challenges as a field. These include the high individual and societal costs of mental illnesses, overlapping and heterogeneous diagnoses, a complete lack of biomarkers, and treatments that, although efficacious for some, leave many without adequate relief. On the other hand, scientific and technical advances present considerable opportunities, especially in genomics, computational and theoretical approaches, and neural circuit technologies. The National Institute of Mental Health is committed to taking advantage of these opportunities to address the challenges of psychiatry, in the service of achieving our mission of transforming the understanding and treatment of mental illnesses.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037523","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37072403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 5
Dorcas Cummings Lecture. 多卡斯·卡明斯阅读。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-04-01 DOI: 10.1101/sqb.2018.83.038091
{"title":"Dorcas Cummings Lecture.","authors":"","doi":"10.1101/sqb.2018.83.038091","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.038091","url":null,"abstract":"Dr. Read Montague presented the Dorcas Cummings lecture entitled “Connecting Mind and Brain in a Computational Age” to friends and neighbors of Cold Spring Harbor Laboratory and Symposium participants on Saturday, June 2, 2018. Dr. Montague is the Vernon Mountcastle Research Professor at Virginia Tech Carilion School of Medicine, Director of the Human Neuroimaging Laboratory and the Computational Psychiatry Unit at the Fralin Biomedical Research Institute VTC, and Honorary Professor at the Wellcome Centre for Human Neuroimaging at University College London.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"229-236"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37112411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Network Explanation of Alzheimer's Regional Vulnerability. 阿尔茨海默病区域脆弱性的网络解释。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-01-14 DOI: 10.1101/sqb.2018.83.036889
Scott A Small, Larry W Swanson
{"title":"A Network Explanation of Alzheimer's Regional Vulnerability.","authors":"Scott A Small,&nbsp;Larry W Swanson","doi":"10.1101/sqb.2018.83.036889","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.036889","url":null,"abstract":"<p><p>Studies in patients and mouse models have pinpointed a precise zone in the cerebral cortex selectively vulnerable to the earliest stages of Alzheimer's disease (AD): the borderzone covering the entorhinal and perirhinal cortical areas. An independent series of studies has revealed that this entorhinal-perirhinal borderzone is a central cortical hub, with a distinct connectivity pattern across the cerebral hemispheres. Here we develop a hypothesis that explains how this distinct network feature interacts with established pathogenic drivers of AD in explaining the disease's regional vulnerability and suggests how it acts as an anatomical source of disease spread.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"193-200"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.036889","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36852952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 11
Benefits of Enhancing Nicotinamide Adenine Dinucleotide Levels in Damaged or Diseased Nerve Cells. 增强受损或病变神经细胞中烟酰胺腺嘌呤二核苷酸水平的益处。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-02-20 DOI: 10.1101/sqb.2018.83.037622
Andrew A Pieper, Steven L McKnight
{"title":"Benefits of Enhancing Nicotinamide Adenine Dinucleotide Levels in Damaged or Diseased Nerve Cells.","authors":"Andrew A Pieper,&nbsp;Steven L McKnight","doi":"10.1101/sqb.2018.83.037622","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037622","url":null,"abstract":"<p><p>Three unbiased lines of research have commonly pointed to the benefits of enhanced levels of nicotinamide adenine dinucleotide (NAD<sup>+</sup>) to diseased or damaged neurons. Mice carrying a triplication of the gene encoding the culminating enzyme in NAD<sup>+</sup> salvage from nicotinamide, NMNAT, are protected from a variety of insults to axons. Protection from Wallerian degeneration of axons is also observed in flies and mice bearing inactivating mutations in the <i>SARM1</i> gene. Functional studies of the <i>SARM1</i> gene product have revealed the presence of an enzymatic activity directed toward the hydrolysis of NAD<sup>+</sup> Finally, an unbiased drug screen performed in living mice led to the discovery of a neuroprotective chemical designated P7C3. Biochemical studies of the P7C3 chemical show that it can enhance recovery of NAD<sup>+</sup> from nicotinamide by activating NAMPT, the first enzyme in the salvage pathway. In combination, these three unrelated research endeavors offer evidence of the benefits of enhanced NAD<sup>+</sup> levels to damaged neurons.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"207-217"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36577547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Adolescence and "Late Blooming" Synapses of the Prefrontal Cortex. 青春期和前额皮质的“晚熟”突触。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-01-23 DOI: 10.1101/sqb.2018.83.037507
Kristen Delevich, A Wren Thomas, Linda Wilbrecht
{"title":"Adolescence and \"Late Blooming\" Synapses of the Prefrontal Cortex.","authors":"Kristen Delevich,&nbsp;A Wren Thomas,&nbsp;Linda Wilbrecht","doi":"10.1101/sqb.2018.83.037507","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037507","url":null,"abstract":"<p><p>The maturation of the prefrontal cortex (PFC) during adolescence is thought to be important for cognitive and affective development and mental health risk. Whereas many summaries of adolescent development have focused on dendritic spine pruning and gray matter thinning in the PFC during adolescence, we highlight recent rodent data from our laboratory and others to call attention to continued synapse formation and plasticity in the adolescent period in specific cell types and circuits. In particular, we highlight changes in inhibitory neurotransmission onto intratelencephalic (IT-type) projecting cortical neurons and late expansion of connectivity between the amygdala and PFC and the ventral tegmental area and PFC. Continued work on these \"late blooming\" synapses in specific cell types and circuits, and their interrelationships, will illuminate new opportunities for understanding and shaping the biology of adolescent development. We also address which aspects of adolescent PFC development are dependent on pubertal processes.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"37-43"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36879842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 34
Computational Underpinnings of Neuromodulation in Humans. 人类神经调节的计算基础。
Cold Spring Harbor symposia on quantitative biology Pub Date : 2018-01-01 Epub Date: 2019-04-25 DOI: 10.1101/sqb.2018.83.038166
P Read Montague, Kenneth T Kishida
{"title":"Computational Underpinnings of Neuromodulation in Humans.","authors":"P Read Montague,&nbsp;Kenneth T Kishida","doi":"10.1101/sqb.2018.83.038166","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.038166","url":null,"abstract":"<p><p>We summarize a new approach to neuromodulator detection that provides colocalized detection of dopamine, serotonin, and norepinephrine at subsecond timescales and promises to provide submillisecond estimates of the same. The methodology, elastic net electrochemistry, is used to estimate dopamine and serotonin in the striatum of conscious human subjects during active decision-making. We show a proof-of-principle example of the same method working on commercially available depth electrodes in common use for epilepsy monitoring and neurosurgical planning in humans, which further promises to make such electrodes sources of fast neuromodulator information never before available in human subjects. We discuss the implications of this methodology for making direct tests in humans of the computations carried by these three important neuromodulatory systems. The methods also promise great utility in model organisms, but this chapter focuses on the possibilities for human use.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"71-82"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.038166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37361603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 17
Toward a Distributed Gallery in the scholarly network 学术网络中的分布式画廊
Cold Spring Harbor symposia on quantitative biology Pub Date : 2017-12-19 DOI: 10.7264/N3B27SQB
J. Cayley
{"title":"Toward a Distributed Gallery in the scholarly network","authors":"J. Cayley","doi":"10.7264/N3B27SQB","DOIUrl":"https://doi.org/10.7264/N3B27SQB","url":null,"abstract":"How can we persuade universities to own their responsibilities to the practice-based research that they patronize — while bringing new, fully-accredited methodologies and infrastructures to Humanities and Arts scholarship? \u0000 \u0000Link to Keynote video: https://youtu.be/BNlmGD8yJhc​","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"1 1","pages":"64"},"PeriodicalIF":0.0,"publicationDate":"2017-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73251625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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