Cold Spring Harbor symposia on quantitative biology最新文献

{"title":"A Conversation with Ricardo Dolmetsch.","authors":"","doi":"10.1101/sqb.2018.83.037515","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037515","url":null,"abstract":"Dr. Dolmetsch: There were at least two things that motivated my change. The first was that I had become very interested in translational research. I have a son who has autism. I had become very interested in identifying mutations that lead to intellectual disability as well as autism, and I’d become very close to the families and I was getting a little frustrated that we weren’t making much progress in terms of trying to come up with treatments. I thought that I needed to be in a place where I could do that. That was one reason. The second reason was that I found that we probably didn’t have the expertise required to pursue some of the scientific questions that I wanted. That wasmostly because we were not really very well set up to try to do studies in humans the way I wanted to do them. So those are the two main motivations for moving.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"246-248"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037515","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37318566","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}

{"title":"Parvalbumin Interneuron Plasticity for Consolidation of Reinforced Learning.","authors":"Matteo Tripodi,&nbsp;Komal Bhandari,&nbsp;Ananya Chowdhury,&nbsp;Arghya Mukherjee,&nbsp;Pico Caroni","doi":"10.1101/sqb.2018.83.037630","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037630","url":null,"abstract":"<p><p>Parvalbumin (PV) basket cells are widespread local interneurons that inhibit principal neurons and each other through perisomatic boutons. They enhance network function and regulate local ensemble activities, particularly in the γ range. Organized network activity is critically important for long-term memory consolidation during a late time window 11-15 h after acquisition. Here, we discuss the role of learning-related plasticity in PV neurons for long-term memory consolidation. The plasticity can lead to enhanced (high-PV) or reduced (low-PV) expression of PV/GAD67. High-PV plasticity is induced upon definite reinforced learning in early-born PV basket cells, whereas low-PV plasticity is induced upon provisional reinforced learning in late-born PV basket cells. The plasticity is first detectable 6 h after acquisition, at the end of a time window for memory specification through experience, and is critically important 11-15 h after acquisition for enhanced network activity and long-term memory consolidation. High- and low-PV plasticity appear to regulate activity in distinct local networks of principal neurons and PV basket cells. These findings suggest how flexibility and stability in learning and memory might be implemented through parallel circuits and networks.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"25-35"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37412039","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}

{"title":"Multiple Dopamine Systems: Weal and Woe of Dopamine.","authors":"Mitsuko Watabe-Uchida,&nbsp;Naoshige Uchida","doi":"10.1101/sqb.2018.83.037648","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037648","url":null,"abstract":"<p><p>The ability to predict future outcomes increases the fitness of the animal. Decades of research have shown that dopamine neurons broadcast reward prediction error (RPE) signals-the discrepancy between actual and predicted reward-to drive learning to predict future outcomes. Recent studies have begun to show, however, that dopamine neurons are more diverse than previously thought. In this review, we will summarize a series of our studies that have shown unique properties of dopamine neurons projecting to the posterior \"tail\" of the striatum (TS) in terms of anatomy, activity, and function. Specifically, TS-projecting dopamine neurons are activated by a subset of negative events including threats from a novel object, send prediction errors for external threats, and reinforce avoidance behaviors. These results indicate that there are at least two axes of dopamine-mediated reinforcement learning in the brain-one learning from canonical RPEs and another learning from threat prediction errors. We argue that the existence of multiple learning systems is an adaptive strategy that makes possible each system optimized for its own needs. The compartmental organization in the mammalian striatum resembles that of a dopamine-recipient area in insects (mushroom body), pointing to a principle of dopamine function conserved across phyla.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"83-95"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36577546","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}

{"title":"A Conversation with Joshua A. Gordon.","authors":"","doi":"10.1101/sqb.2018.83.037291","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037291","url":null,"abstract":"Dr. Gordon: I spoke generally about what I perceive as the challenges and opportunities in psychiatric neuroscience. In particular, we in psychiatry—in trying to understand our disorders and help our patients—have significant challenges that we face around the burden of our disease, around challenges in terms of diagnoses and whether they correspond to the real entities that are causing people’s suffering. In terms of what we call biomarkers, tests that we can do in people to help diagnose them or guide treatment decisions, we have none. And our treatments, although they generally do work for many people, don’t work well enough for many and don’t work for a significant chunk of the patients who need help. You put those together and we face considerable challenges in terms of trying to help people who are suffering from mental illnesses. The opportunities, though, are equally impressive. We now have, in the area of genetics, knowledge of 200+ places in the genome that predispose to various psychiatric illnesses, included schizophrenia, bipolar disorder, and depression. Each one of those places in the genome that’s associated with psychiatric disorder represents a clue as to the biology underlying the disorders, and those clues are then opportunities for us to understand and potentially develop treatments for these illnesses. We also face tremendous opportunity in a specific area of neuroscience that’s really blossomed in the last 10 years, circuit neuroscience, wherewe’ve gained—at least in mice —the ability to monitor and modulate neural activity in very precise parts of the brain. Not just anatomical parts, but neuron-specific cells in the nervous system, specific projections, specific wires within the nervous system that have allowed us to dissect the elements of the brain that control behavior. The hope is that, in understanding those elements, we can develop knowledge or treatments for psychiatric illness. The third area that presents a unique opportunity for psychiatry are computational and theoretical approaches. We have “big data” approaches, machine learning approaches, but also modeling approaches and theoretical approaches that allow us to ask questions about how the brain produces behavior and how that might go awry in psychiatric illness with greater sophistication and greater precision. So I think if we are able to exploit genetics, neural circuits, and computational approaches, we can make progress more rapidly than we’ve been able to do in the past.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"255-257"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037291","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36852953","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}

{"title":"A Conversation with Michel Goedert.","authors":"","doi":"10.1101/sqb.2018.83.037358","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037358","url":null,"abstract":"Michel Goedert: It was probably even earlier. I believe we first met at the conference on “The Molecular Biology of Alzheimer’s Disease,” at Banbury in April 1988, which was my first meeting on Alzheimer’s disease. We (Aaron Klug, Claude Wischik, and I) reported the presence of tau protein in paired helical filaments. Our papers had been accepted for publication, but they hadn’t been published yet. So the work came as a surprise to many of the people who were there, because they didn’t know we were doing this. Today, the 1st of June, it is exactly 30 years since the first of those three papers was published.","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"252-254"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36853565","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}

{"title":"Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression?","authors":"Zelah Joel,&nbsp;Pablo Izquierdo,&nbsp;Dervis A Salih,&nbsp;Jill C Richardson,&nbsp;Damian M Cummings,&nbsp;Frances A Edwards","doi":"10.1101/sqb.2018.83.037531","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037531","url":null,"abstract":"<p><p>Mouse models of Alzheimer's disease have commonly used transgenic overexpression of genes involved in production of amyloid β (<i>APP</i> and/or <i>PSEN1/2</i>) or Tau (<i>MAPT</i>) with mutations that result in familial forms of dementia. We discuss possible improvements that may create full models while avoiding the problems of overexpression and report synaptic results in APPKI models. We stress use of inappropriate controls without overexpression of the normal human protein and the mismatch between the learning deficits reported in mice with plaques but no tangles and the human condition. We focus on Tau overexpression, including new data that support previous reports of the grossly nonlinear relationship between Tau overexpression and neurofibrillary tangle load, with a twofold increase in Tau protein, resulting in a 100-fold increase in tangle density. These data also support the hypothesis that a high concentration of soluble Tau, in overexpression models, plays an important direct role in neurodegeneration, rather than only via aggregation. Finally, we hypothesize that there is an optimal concentration range over which Tau can bind to microtubules and a threshold beyond which much of the overexpressed protein is unable to bind. The excess thus causes toxicity in ways not necessarily related to the process in human dementias.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"151-161"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037531","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36953504","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}

{"title":"The Synaptomic Theory of Behavior and Brain Disease.","authors":"Seth G N Grant","doi":"10.1101/sqb.2018.83.037887","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037887","url":null,"abstract":"<p><p>The purpose of this article is to outline a new molecular and synaptic theory of behavior called the \"synaptomic theory,\" named because it is centered on the synaptome-the complement of synapses in the brain. Synaptomic theory posits that synapses are structures of high molecular complexity and vast diversity that are observable in maps of the brain and that these synaptome maps are fundamental to behavior. Synaptome maps are a means of writing or storing information that can be retrieved by the patterns of activity that stimulate synapses. Synaptome maps have the capacity to store large amounts of information, including multiple representations within the same map. The dynamic properties of synapses allow synaptome maps to store dynamic sequences of representations that could serve to program behavioral sequences. Synaptome maps are genetically programmed and experience-dependent, thereby storing innate and learned behaviors, respectively. Although learning occurs by modification of the synapse proteome, it does not require long-term potentiation (LTP) of synaptic weight or growth of new synapses, and the theory predicts that LTP modulates information recall. The spatial architecture of synaptome maps arise from an underlying molecular hierarchy linking the genome to the supramolecular assembly of proteins into complexes and supercomplexes. This molecular hierarchy can explain how genome evolution results in the behavioral repertoire of the organism. Mutations disrupting this molecular hierarchy change the architecture of synaptome maps, potentially accounting for the behavioral phenotypes associated with neurological and psychiatric disorders.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"45-56"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37069575","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}

{"title":"Distinct Conformers of Assembled Tau in Alzheimer's and Pick's Diseases.","authors":"Michel Goedert,&nbsp;Benjamin Falcon,&nbsp;Wenjuan Zhang,&nbsp;Bernardino Ghetti,&nbsp;Sjors H W Scheres","doi":"10.1101/sqb.2018.83.037580","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037580","url":null,"abstract":"<p><p>Tau filaments with distinct morphologies and/or isoform compositions underlie a large number of human neurodegenerative diseases. In conjunction with experimental studies, this has led to the suggestion that conformers of aggregated tau exist. Electron cryo-microscopy can be used to determine high-resolution structures of amyloid filaments from human brain. Paired helical and straight tau filaments of Alzheimer's disease (AD) are ultrastructural polymorphs. Each filament core is composed of two identical protofilaments extending from G273/304-E380 (in the numbering of the 441-amino acid isoform of human tau), which adopt a combined cross-β/β-helix structure. They comprise the ends of the first or second microtubule-binding repeat (R1 or R2), the whole of R3 and R4, and 12 amino acids after R4. In contrast, the core of the narrow filaments of Pick's disease (PiD) consists of a single protofilament extending from K254-F378 of 3R tau, which adopts a cross-β structure. It comprises the last 21 amino acids of R1, all of R3 and R4, and 10 amino acids after R4. Wide tau filaments of PiD, which are in the minority, consist of two narrow filaments packed against each other. The tau filament folds of AD and PiD appear to be conserved between different cases of disease. These findings show that filamentous tau adopts one fold in AD and a different fold in PiD, establishing the existence of distinct conformers.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"163-171"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037580","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37069577","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}

{"title":"A Conversation with Beth Stevens.","authors":"","doi":"10.1101/sqb.2018.83.037861","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.037861","url":null,"abstract":"Sejal Vyas: You work on microglia and synaptic pruning, both in normal development and also in various neurolog-ical disorders. Can you give a brief overview on what are microglia? What are their developmental origins and basic functions?","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"280-283"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.037861","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37112412","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}

{"title":"Neuropeptidergic Control of an Internal Brain State Produced by Prolonged Social Isolation Stress.","authors":"Moriel Zelikowsky,&nbsp;Keke Ding,&nbsp;David J Anderson","doi":"10.1101/sqb.2018.83.038109","DOIUrl":"https://doi.org/10.1101/sqb.2018.83.038109","url":null,"abstract":"<p><p>Prolonged periods of social isolation can generate an internal state that exerts profound effects on the brain and behavior. However, the neurobiological underpinnings of protracted social isolation have been relatively understudied. Here, we review recent literature implicating peptide neuromodulators in the establishment and maintenance of such internal states. More specifically, we describe an evolutionarily conserved role for the neuropeptide tachykinin in the control of social isolation-induced aggression and review recent data that elucidate the manner by which Tac2 controls the widespread effects of social isolation on behavior in mice. Last, we discuss potential roles for additional neuromodulators in controlling social isolation and a more general role for Tac2 in the response to other forms of stress.</p>","PeriodicalId":72635,"journal":{"name":"Cold Spring Harbor symposia on quantitative biology","volume":"83 ","pages":"97-103"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1101/sqb.2018.83.038109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37122568","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}