Progress in Neurobiology最新文献

Opposing effects of nicotine on hypothalamic arcuate nucleus POMC and NPY neurons 尼古丁对下丘脑弓状核 POMC 和 NPY 神经元的相反作用

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102682

引用次数: 0

Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation 安杰尔曼综合征模型小鼠突触可塑性的改变可通过 5-HT7R 刺激得到缓解。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-11-01 DOI: 10.1016/j.pneurobio.2024.102684

{"title":"Alterations of synaptic plasticity in Angelman syndrome model mice are rescued by 5-HT7R stimulation","authors":"","doi":"10.1016/j.pneurobio.2024.102684","DOIUrl":"10.1016/j.pneurobio.2024.102684","url":null,"abstract":"<div><div>Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by motor disfunction, seizures, intellectual disability, speech deficits, and autism-like behavior, showing high comorbidity with Autism Spectrum Disorders (ASD). It is known that stimulation of the serotonin receptor 7 (5-HT7R) can rescue some of the behavioral and neuroplasticity dysfunctions in animal models of Fragile X and Rett syndrome, two pathologies associated with ASD. In view of these observations, we hypothesised that alterations of 5-HT7R signalling might also be involved in AS. To test this hypothesis, we stimulated 5-HT7R with the selective agonist LP-211 to investigate its possible beneficial effects on synaptic dysfunctions and altered behavior in the AS mice model. In mutant mice, we observed impairment of the synaptic machinery of protein synthesis, which was reversed by 5-HT7R activation. Moreover, stimulation of 5-HT7R was able to: i) enhance dendritic spine density in hippocampal neurons, which was reduced in AS mice; ii) restore impaired long-term potentiation (LTP) in hippocampal slices of the AS mice; iii) improve cognitive performance of the mutant animals subjected to the fear conditioning paradigm. Altogether, our results, showing beneficial effects of 5-HT7R stimulation in restoring molecular and cognitive deficits associated with AS, suggest that targeting 5-HT7R could be a promising therapeutic approach for the pathology.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior 操纵核团核心的 radixin 磷酸化可调节风险选择行为。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-20 DOI: 10.1016/j.pneurobio.2024.102681

{"title":"Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior","authors":"","doi":"10.1016/j.pneurobio.2024.102681","DOIUrl":"10.1016/j.pneurobio.2024.102681","url":null,"abstract":"<div><div>Ezrin-Radixin-Moesin (ERM) proteins are actin-binding proteins that contribute to morphological changes in dendritic spines. Despite their significant role in regulating spine structure, the role of ERM proteins in the nucleus accumbnes (NAcc) is not well known, especially in in the context of risk-reward decision-making. Here, we measured the relationship between synaptic excitation and inhibition (E/I ratio) from medium spiny neurons in the NAcc core obtained in the rat after a rat gambling task (rGT). Then, after surgery of a phosphomimetic pseudo-active mutant form of radixin (Rdx-T564D) in the NAcc core, we examined its role in synaptic plasticity and the accompanying risk-choice behavior in rGT. We found that basal E/I ratio in the NAcc core was higher in risk-averse rats than risk-seeking rats. However, it was significantly reduced in risk-averse rats similar to that in risk-seeking rats in the presence of Rdx-T564D in the NAcc core. Furthermore, the head sizes of spines were shifted in risk-averse rats expressing Rdx-T564D in the NAcc core, similar to those observed in risk-seeking rats. The effects of Rdx-T564D in risk-averse rats were again manifested as behavioral changes, with reduced selection of optimal choices and increased selection of disadvantageous ones. In this study, we demonstrated that manipulation of radixin phosphorylation status in the NAcc core can alter glutamatergic synaptic transmission and spine structure at this site, as well as risk choice behaviors in the rGT. These novel findings illustrate that radixin in the NAcc core plays a significant role in determining risk preference during the rGT.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2ALS phenotypes in Drosophila melanogaster 抑制ERO1A可减轻神经元ER压力并改善黑腹果蝇的UBQLN2ALS表型

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-10 DOI: 10.1016/j.pneurobio.2024.102674

{"title":"ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2ALS phenotypes in Drosophila melanogaster","authors":"","doi":"10.1016/j.pneurobio.2024.102674","DOIUrl":"10.1016/j.pneurobio.2024.102674","url":null,"abstract":"<div><div>Modulating the ER stress pathway holds therapeutic promise for neurodegenerative diseases; however, identifying optimal targets remains challenging. In this study, we conducted an unbiased screening to systematically search for commonly up-regulated proteins in ER stress-related neurodegenerative conditions, with endoplasmic reticulum oxidoreductase 1 alpha (ERO1A) emerging as a significant hit. Further experiments conducted in the model organism <em>Drosophila melanogaster</em> demonstrated that elevated levels of <em>Drosophila</em> ERO1A (ERO1L) were indeed detrimental to neurons. Conversely, genetic suppression or pharmacological inhibition of ERO1L activity provided neuroprotection under ER stress and extended the lifespan of flies. To translate these findings, we performed a genetic modifier screening and underscored significant neuroprotective effects against UBQLN2<sup>ALS</sup> pathology. Additionally, administration of the chemical probe inhibitor of ERO1A, known as EN460, enhanced locomotive functions and neuromuscular junction (NMJ) morphology in <em>Drosophila</em> UBQLN2<sup>ALS</sup> model. Mechanistically, targeting ERO1L during environmental or pathological ER stress mitigated proteotoxic stress by lowering either the PERK or IRE1 branches of the unfolded protein response (UPR). These findings suggest ERO1A as a promising therapeutic target in UBQLN2<sup>ALS</sup> and other ER stress-related conditions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuronal threshold functions: Determining symptom onset in neurological disorders 神经元阈值功能：确定神经系统疾病的症状发作。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-09 DOI: 10.1016/j.pneurobio.2024.102673

{"title":"Neuronal threshold functions: Determining symptom onset in neurological disorders","authors":"","doi":"10.1016/j.pneurobio.2024.102673","DOIUrl":"10.1016/j.pneurobio.2024.102673","url":null,"abstract":"<div><div>Synaptic networks determine brain function. Highly complex interconnected brain synaptic networks provide output even under fluctuating or pathological conditions. Relevant to the treatment of brain disorders, understanding the limitations of such functional networks becomes paramount. Here we use the example of Parkinson’s Disease (PD) as a system disorder, with PD symptomatology emerging only when the functional reserves of neurons, and their interconnected networks, are unable to facilitate effective compensatory mechanisms. We have denoted this the “threshold theory” to account for how PD symptoms develop in sequence. In this perspective, threshold functions are delineated in a quantitative, synaptic, and cellular network context. This provides a framework to discuss the development of specific symptoms. PD includes dysfunction and degeneration in many organ systems and both peripheral and central nervous system involvement. The threshold theory accounts for and explains the reasons why parallel gradually emerging pathologies in brain and peripheral systems generate specific symptoms only when functional thresholds are crossed, like tipping points. New and mounting evidence demonstrate that PD and related neurodegenerative diseases are multisystem disorders, which transcends the traditional brain-centric paradigm. We believe that representation of threshold functions will be helpful to develop new medicines and interventions that are specific for both pre- and post-symptomatic periods of neurodegenerative disorders.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A tradeoff between efficiency and robustness in the hippocampal-neocortical memory network during human and rodent sleep 人类和啮齿动物睡眠时海马-皮层记忆网络的效率和稳健性之间的权衡。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-04 DOI: 10.1016/j.pneurobio.2024.102672

{"title":"A tradeoff between efficiency and robustness in the hippocampal-neocortical memory network during human and rodent sleep","authors":"","doi":"10.1016/j.pneurobio.2024.102672","DOIUrl":"10.1016/j.pneurobio.2024.102672","url":null,"abstract":"<div><div>Sleep constitutes a brain state of disengagement from the external world that supports memory consolidation and restores cognitive resources. The precise mechanisms how sleep and its varied stages support information processing remain largely unknown. Synaptic scaling models imply that daytime learning accumulates neural information, which is then consolidated and downregulated during sleep. Currently, there is a lack of in-vivo data from humans and rodents that elucidate if, and how, sleep renormalizes information processing capacities. From an information-theoretical perspective, a consolidation process should entail a reduction in neural pattern variability over the course of a night. Here, in a cross-species intracranial study, we identify a tradeoff in the neural population code during sleep where information coding efficiency is higher in the neocortex than in hippocampal archicortex in humans than in rodents as well as during wakefulness compared to sleep. Critically, non-REM sleep selectively reduces information coding efficiency through pattern repetition in the neocortex in both species, indicating a transition to a more robust information coding regime. Conversely, the coding regime in the hippocampus remained consistent from wakefulness to non-REM sleep. These findings suggest that new information could be imprinted to the long-term mnemonic storage in the neocortex through pattern repetition during sleep. Lastly, our results show that task engagement increased coding efficiency, while medically-induced unconsciousness disrupted the population code. In sum, these findings suggest that neural pattern variability could constitute a fundamental principle underlying cognitive engagement and memory formation, while pattern repetition reflects robust coding, possibly underlying the consolidation process.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “The Reelin receptor ApoER2 is a cargo for the adaptor protein complex AP-4: Implications for hereditary spastic paraplegia” [Progr. Neurobiol. 234(2024)102575] Reelin受体ApoER2是适配蛋白复合物AP-4的载体：对遗传性痉挛性截瘫的影响"[Progr. Neurobiol.

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102662

引用次数: 0

The role of frontopolar cortex in adjusting the balance between response execution and action inhibition in anthropoids 前额极皮层在调整猿类反应执行和动作抑制之间平衡中的作用。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102671

{"title":"The role of frontopolar cortex in adjusting the balance between response execution and action inhibition in anthropoids","authors":"","doi":"10.1016/j.pneurobio.2024.102671","DOIUrl":"10.1016/j.pneurobio.2024.102671","url":null,"abstract":"<div><div>Executive control of behaviour entails keeping a fine balance between response execution and action inhibition. The most anterior part of the prefrontal cortex (frontopolar cortex) is highly developed in anthropoids; however, no previous study has examined its essential (indispensable) role in regulating the interplay between action execution and inhibition. In this cross-species study, we examine the performance of humans and macaque monkeys in the context of a stop-signal task and then assess the consequence of selective and bilateral damage to frontopolar cortex on monkeys’ behaviour. Humans and monkeys showed significant within-session practice-related adjustments in both response execution (increase in response time (RT) and decrease in response variabilities) and action inhibition (enhanced inhibition). Furthermore, both species expressed context-dependent (post-error and post-stop) behavioral adjustments. In post-lesion testing, frontopolar-damaged monkeys had a longer RT and lower percentage of timeout trials, compared to their pre-lesion performance. The practice-related changes in mean RT and in RT variability were significantly heightened in frontopolar-damaged monkeys. They also showed attenuated post-error, but exaggerated post-stop, behavioural adjustments. Importantly, frontopolar damage had no significant effects on monkeys’ inhibition ability. Our findings indicate that frontopolar cortex plays a critical role in allocation of control to response execution, but not action inhibition.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sparse representation of neurons for encoding complex sounds in the auditory cortex 听觉皮层中编码复杂声音的神经元稀疏表征。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102661

{"title":"Sparse representation of neurons for encoding complex sounds in the auditory cortex","authors":"","doi":"10.1016/j.pneurobio.2024.102661","DOIUrl":"10.1016/j.pneurobio.2024.102661","url":null,"abstract":"<div><div>Listening in complex sound environments requires rapid segregation of different sound sources, e.g., having a conversation with multiple speakers or other environmental sounds. Efficient processing requires fast encoding of inputs to adapt to target sounds and identify relevant information from past experiences. This adaptation process represents an early phase of implicit learning of the sound statistics to form auditory memory. The auditory cortex (ACtx) plays a crucial role in this implicit learning process, but the underlying circuits are unknown. In awake mice, we recorded neuronal responses in different ACtx subfields using in vivo 2-photon imaging of excitatory and inhibitory (parvalbumin; PV) neurons. We used a paradigm adapted from human studies that induced rapid implicit learning from passively presented complex sounds and imaged A1 Layer 4 (L4), A1 L2/3, and A2 L2/3. In this paradigm, a frozen spectro-temporally complex <em>‘Target’</em> sound randomly re-occurred within a stream of other random complex sounds. All ACtx subregions contained distinct groups of cells specifically responsive to complex acoustic sequences, indicating that even thalamocortical input layers (A1 L4) respond to complex sounds. Subgroups of excitatory and inhibitory cells in all subfields showed decreased responses for re-occurring Target sounds, indicating that ACtx is highly involved in the early implicit learning phase. At the population level, activity was more decorrelated to Target sounds independent of the duration of frozen token, subregions, and cell type. These findings suggest that ACtx and its input layers contribute to the early phase of auditory memory for complex sounds, suggesting a parallel strategy across ACtx areas and between excitatory and inhibitory neurons.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple dimensions of syntactic structure are resolved earliest in posterior temporal cortex 句法结构的多个维度最早在后颞叶皮层得到解析。

IF 6.7 2区医学

Progress in Neurobiology Pub Date : 2024-10-01 DOI: 10.1016/j.pneurobio.2024.102669

{"title":"Multiple dimensions of syntactic structure are resolved earliest in posterior temporal cortex","authors":"","doi":"10.1016/j.pneurobio.2024.102669","DOIUrl":"10.1016/j.pneurobio.2024.102669","url":null,"abstract":"<div><div>How we combine minimal linguistic units into larger structures remains an unresolved topic in neuroscience. Language processing involves the abstract construction of ‘vertical’ and ‘horizontal’ information simultaneously (e.g., phrase structure, morphological agreement), but previous paradigms have been constrained in isolating only one type of composition and have utilized poor spatiotemporal resolution. Using intracranial recordings, we report multiple experiments designed to separate phrase structure from morphosyntactic agreement. Epilepsy patients (n = 10) were presented with auditory two-word phrases grouped into pseudoword-verb (‘trab run’) and pronoun-verb either with or without Person agreement (‘they run’ vs. ‘they runs’). Phrase composition and Person violations both resulted in significant increases in broadband high gamma activity approximately 300 ms after verb onset in posterior middle temporal gyrus (pMTG) and posterior superior temporal sulcus (pSTS), followed by inferior frontal cortex (IFC) at 500 ms. While sites sensitive to only morphosyntactic violations were distributed, those sensitive to both composition types were generally confined to pSTS/pMTG and IFC. These results indicate that posterior temporal cortex shows the earliest sensitivity for hierarchical linguistic structure across multiple dimensions, providing neural resources for distinct windows of composition. This region is comprised of sparsely interwoven heterogeneous constituents that afford cortical search spaces for dissociable syntactic relations.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0