Neuroscientist最新文献

{"title":"Perspectives on Neuroscience and Behavior.","authors":"","doi":"10.1177/10738584231190621","DOIUrl":"10.1177/10738584231190621","url":null,"abstract":"The serendipitous discovery that lithium could treat bipolar disorder (BD) was published in 1949. In 1967, a published diagrammatic display of the clinical course of 88 patients with BP treated with lithium for one to six years depicted lithium’s extremely robust efficacy in preventing BP episodes, but there was also considerable variability across patients. In 1970, a five-month double-blind withdrawal study of lithium was published in which half of stable 50 patients with BD and 34 patients with recurrent depression were switched from lithium to placebo. Relapse occurred in 21 on placebo and none on lithium, which unequivocally demonstrated the robust efficacy of lithium in preventing relapse in BD and recurrent depression. Over the past 53 years, there have been an extensive number of studies attempting to discover the mechanism by which lithium produces such an important therapeutic effect. Now, in an outstanding and penetrating mechanistic study, it has been found that in two mouse models of ankyrin-G (AnkG) deficiency that displayed decreased dendritic complexity and decreased dendritic spine numbers in cortical neurons, lithium treatment corrected both abnormalities in both models. In the cortical neuron culture model with AnkG knockdown, a selective glycogen synthase kinase 3β (GSK3β) inhibitor rescued the spine morphology defects but not the dendritic complexity, and forskolin, which increases cAMP, rescued the dendritic complexity but not the spine morphology. A synergistic effect of both drugs was required to correct both the spine morphology and dendritic complexity (Piguel and others 2023). These findings are an important advance, since the ANK3 gene is linked to BD, single-nucleotide polymorphisms within the ANK3 regulatory domains have been found to be associated with lithium response in patients with BP, and mouse ANK3 knockout models have behavioral features like BD that respond to lithium treatment. Lithium directly or indirectly, through autoinhibition, acts to inhibit GSK3β, and it rescues several behavioral deficits like BD in ANKG knockout mice. In addition, lithium increases cAMP levels in frontal cortex. It should now be possible to assess the effects of lithium in individuals with BP who have genetic AnkG abnormalities to see if they have a more beneficial therapeutic response. Most important, the discovery that lithium’s mechanism of action involves both GSK3β inhibition and increased cAMP can help guide new research to discover alternatives to lithium, because lithium has so many toxic side effects.","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"517"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perineuronal Nets: Subtle Structures with Large Implications.","authors":"Héctor Carceller,&nbsp;Yaiza Gramuntell,&nbsp;Patrycja Klimczak,&nbsp;Juan Nacher","doi":"10.1177/10738584221106346","DOIUrl":"10.1177/10738584221106346","url":null,"abstract":"<p><p>Perineuronal nets (PNNs) are specialized structures of the extracellular matrix that surround the soma and proximal dendrites of certain neurons in the central nervous system, particularly parvalbumin-expressing interneurons. Their appearance overlaps the maturation of neuronal circuits and the closure of critical periods in different regions of the brain, setting their connectivity and abruptly reducing their plasticity. As a consequence, the digestion of PNNs, as well as the removal or manipulation of their components, leads to a boost in this plasticity and can play a key role in the functional recovery from different insults and in the etiopathology of certain neurologic and psychiatric disorders. Here we review the structure, composition, and distribution of PNNs and their variation throughout the evolutive scale. We also discuss methodological approaches to study these structures. The function of PNNs during neurodevelopment and adulthood is discussed, as well as the influence of intrinsic and extrinsic factors on these specialized regions of the extracellular matrix. Finally, we review current data on alterations in PNNs described in diseases of the central nervous system (CNS), focusing on psychiatric disorders. Together, all the data available point to the PNNs as a promising target to understand the physiology and pathologic conditions of the CNS.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"569-590"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"José Manuel Rodríguez Delgado, Walter Freeman, and Psychosurgery: A Study in Contrasts.","authors":"Joseph J Fins,&nbsp;John S Vernaglia","doi":"10.1177/10738584221086603","DOIUrl":"10.1177/10738584221086603","url":null,"abstract":"<p><p>History has conflated the legacies of José Manuel Rodríguez Delgado and Walter Freeman, midcentury proponents of somatic therapies for neuropsychiatric conditions. Both gained notoriety: Delgado after he appeared on the front page of the <i>New York Times</i> having used his <i>stimoceiver</i> to stop a charging bull in Spain; Freeman as the proponent of lobotomy. Both were the object of critique by the antipsychiatry movement and those who felt that their methods and objectives posed a threat to personal liberty. Using archival sources, we demonstrate that this conflation is a misrepresentation of the historical record and that their methods, objectives, ethics, and philosophical commitments differed widely. Accurate knowledge about historical antecedents is a predicate for ethical analysis and becomes especially relevant information as neuroscience develops circuit-based treatments for conditions such as Parkinson disease, depression, and brain injury. Part of that corrective is to counter the conflation of Delgado's and Freeman's life and work. Appreciating their distinctive legacies can help guide neuropsychiatric research done today that might yet haunt future generations.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 5","pages":"518-531"},"PeriodicalIF":5.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10436749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prefrontal Cortical Control of Anxiety: Recent Advances.","authors":"Nancy R Mack,&nbsp;Suixin Deng,&nbsp;Sha-Sha Yang,&nbsp;Yousheng Shu,&nbsp;Wen-Jun Gao","doi":"10.1177/10738584211069071","DOIUrl":"https://doi.org/10.1177/10738584211069071","url":null,"abstract":"<p><p>Dysfunction in the prefrontal cortex is commonly implicated in anxiety disorders, but the mechanisms remain unclear. Approach-avoidance conflict tasks have been extensively used in animal research to better understand how changes in neural activity within the prefrontal cortex contribute to avoidance behaviors, which are believed to play a major role in the maintenance of anxiety disorders. In this article, we first review studies utilizing <i>in vivo</i> electrophysiology to reveal the relationship between changes in neural activity and avoidance behavior in rodents. We then review recent studies that take advantage of optical and genetic techniques to test the unique contribution of specific prefrontal cortex circuits and cell types to the control of anxiety-related avoidance behaviors. This new body of work reveals that behavior during approach-avoidance conflict is dynamically modulated by individual cell types, distinct neural pathways, and specific oscillatory frequencies. The integration of these different pathways, particularly as mediated by interactions between excitatory and inhibitory neurons, represents an exciting opportunity for the future of understanding anxiety.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"488-505"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869286/pdf/nihms-1863656.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ongoing Brain Activity and Its Role in Cognition: Dual versus Baseline Models.","authors":"Georg Northoff,&nbsp;Deniz Vatansever,&nbsp;Andrea Scalabrini,&nbsp;Emmanuel A Stamatakis","doi":"10.1177/10738584221081752","DOIUrl":"https://doi.org/10.1177/10738584221081752","url":null,"abstract":"<p><p>What is the role of the brain's ongoing activity for cognition? The predominant perspectives associate ongoing brain activity with resting state, the default-mode network (DMN), and internally oriented mentation. This triad is often contrasted with task states, non-DMN brain networks, and externally oriented mentation, together comprising a \"dual model\" of brain and cognition. In opposition to this duality, however, we propose that ongoing brain activity serves as a neuronal baseline; this builds upon Raichle's original search for the default mode of brain function that extended beyond the canonical default-mode brain regions. That entails what we refer to as the \"baseline model.\" Akin to an internal biological clock for the rest of the organism, the ongoing brain activity may serve as an internal point of reference or standard by providing a shared neural code for the brain's rest as well as task states, including their associated cognition. Such shared neural code is manifest in the spatiotemporal organization of the brain's ongoing activity, including its global signal topography and dynamics like intrinsic neural timescales. We conclude that recent empirical evidence supports a baseline model over the dual model; the ongoing activity provides a global shared neural code that allows integrating the brain's rest and task states, its DMN and non-DMN, and internally and externally oriented cognition.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"393-420"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10052369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forthcoming Articles.","authors":"","doi":"10.1177/10738584231179065","DOIUrl":"https://doi.org/10.1177/10738584231179065","url":null,"abstract":"","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"388-389"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9693805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>The Neuroscientist</i> Comments.","authors":"","doi":"10.1177/10738584231178681","DOIUrl":"https://doi.org/10.1177/10738584231178681","url":null,"abstract":"","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"390"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9751710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>The Neuroscientist</i> Comments.","authors":"","doi":"10.1177/10738584231178682","DOIUrl":"https://doi.org/10.1177/10738584231178682","url":null,"abstract":"The NeuroscieNTisT commeNTs ~ The NeuroscieNTisT commeNTs~ The NeuroscieNTisT commeNTs T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s ~ T h e N e u r o s c ie N T is T c o m m e N T s A Dynamic Astrocyte Chloride Reservoir: Regulating Inhibitory Neurotransmission during Sustained Neuronal","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"391"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Insights on Glutamatergic Dysfunction in Alzheimer's Disease and Therapeutic Implications.","authors":"Priyanka D Pinky,&nbsp;Jeremiah C Pfitzer,&nbsp;Jared Senfeld,&nbsp;Hao Hong,&nbsp;Subhrajit Bhattacharya,&nbsp;Vishnu Suppiramaniam,&nbsp;Irfan Qureshi,&nbsp;Miranda N Reed","doi":"10.1177/10738584211069897","DOIUrl":"https://doi.org/10.1177/10738584211069897","url":null,"abstract":"<p><p>Alzheimer's disease (AD) poses a critical public health challenge, and there is an urgent need for novel treatment options. Glutamate, the principal excitatory neurotransmitter in the human brain, plays a critical role in mediating cognitive and behavioral functions; and clinical symptoms in AD patients are highly correlated with the loss of glutamatergic synapses. In this review, we highlight how dysregulated glutamatergic mechanisms can underpin cognitive and behavioral impairments and contribute to the progression of AD via complex interactions with neuronal and neural network hyperactivity, Aβ, tau, glial dysfunction, and other disease-associated factors. We focus on the tripartite synapse, where glutamatergic neurotransmission occurs, and evidence elucidating how the tripartite synapse can be pathologically altered in AD. We also discuss promising therapeutic approaches that have the potential to rescue these deficits. These emerging data support the development of novel glutamatergic drug candidates as compelling approaches for treating AD.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"461-471"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9700073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sculpting Astrocyte Diversity through Circuits and Transcription.","authors":"Yi-Ting Cheng,&nbsp;Junsung Woo,&nbsp;Benjamin Deneen","doi":"10.1177/10738584221082620","DOIUrl":"https://doi.org/10.1177/10738584221082620","url":null,"abstract":"<p><p>Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the lens of brain region-specific circuits. We articulate our understanding of how transcriptional mechanisms regulate this diversity and key areas that need further exploration to achieve the overarching goal of a functional taxonomy of astrocytes in the brain.</p>","PeriodicalId":49753,"journal":{"name":"Neuroscientist","volume":"29 4","pages":"445-460"},"PeriodicalIF":5.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526762/pdf/nihms-1808875.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10289001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}