Progress in Neurobiology最新文献

{"title":"Decoding the influence of central LEAP2 on food intake and its effect on accumbal dopamine release","authors":"Maximilian Tufvesson-Alm,&nbsp;Qian Zhang,&nbsp;Cajsa Aranäs,&nbsp;Sebastian Blid Sköldheden,&nbsp;Christian E. Edvardsson,&nbsp;Elisabet Jerlhag","doi":"10.1016/j.pneurobio.2024.102615","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102615","url":null,"abstract":"<div><p>The gut-brain peptide ghrelin and its receptor are established as a regulator of hunger and reward-processing. However, the recently recognized ghrelin receptor inverse agonist, liver-expressed antimicrobial peptide 2 (LEAP2), is less characterized. The present study aimed to elucidate LEAP2s central effect on reward-related behaviors through feeding and its mechanism. LEAP2 was administrated centrally in mice and effectively reduced feeding and intake of palatable foods. Strikingly, LEAP2s effect on feeding was correlated to the preference of the palatable food. Further, LEAP2 reduced the rewarding memory of high preference foods, and attenuated the accumbal dopamine release associated with palatable food exposure and eating. Interestingly, LEAP2 was widely expressed in the brain, and particularly in reward-related brain areas such as the laterodorsal tegmental area (LDTg). This expression was markedly altered when allowed free access to palatable foods. Accordingly, infusion of LEAP2 into LDTg was sufficient to transiently reduce acute palatable food intake. Taken together, the present results show that central LEAP2 has a profound effect on dopaminergic reward signaling associated with food and affects several aspects of feeding. The present study highlights LEAP2s effect on reward, which may have applications for obesity and other reward-related psychiatric and neurological disorders.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102615"},"PeriodicalIF":6.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000510/pdfft?md5=04123e9ab2abf3d1946dbb598f752cb2&pid=1-s2.0-S0301008224000510-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638311","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}

{"title":"C3aR in the medial prefrontal cortex modulates the susceptibility to LPS-induced depressive-like behaviors through glutamatergic neuronal excitability","authors":"Rui Sun ,&nbsp;Meng-Yu Tang ,&nbsp;Dan Yang ,&nbsp;Yan-Yi Zhang ,&nbsp;Yi-Heng Xu ,&nbsp;Yong Qiao ,&nbsp;Bin Yu ,&nbsp;Shu-Xia Cao ,&nbsp;Hao Wang ,&nbsp;Hui-Qian Huang ,&nbsp;Hong Zhang ,&nbsp;Xiao-Ming Li ,&nbsp;Hong Lian","doi":"10.1016/j.pneurobio.2024.102614","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102614","url":null,"abstract":"<div><p>Complement activation and prefrontal cortical dysfunction both contribute to the pathogenesis of major depressive disorder (MDD), but their interplay in MDD is unclear. We here studied the role of complement C3a receptor (C3aR) in the medial prefrontal cortex (mPFC) and its influence on depressive-like behaviors induced by systematic lipopolysaccharides (LPS) administration. C3aR knockout (KO) or intra-mPFC C3aR antagonism confers resilience, whereas C3aR expression in mPFC neurons makes KO mice susceptible to LPS-induced depressive-like behaviors. Importantly, the excitation and inhibition of mPFC neurons have opposing effects on depressive-like behaviors, aligning with increased and decreased excitability by C3aR deletion and activation in cortical neurons. In particular, inhibiting mPFC glutamatergic (mPFC^Glu) neurons, the main neuronal subpopulation expresses C3aR, induces depressive-like behaviors in saline-treated WT and KO mice, but not in LPS-treated KO mice. Compared to hypoexcitable mPFC^Glu neurons in LPS-treated WT mice, C3aR-null mPFC^Glu neurons display hyperexcitability upon LPS treatment, and enhanced excitation of mPFC^Glu neurons is anti-depressant, suggesting a protective role of C3aR deficiency in these circumstances. In conclusion, C3aR modulates susceptibility to LPS-induced depressive-like behaviors through mPFC^Glu neuronal excitability. This study identifies C3aR as a pivotal intersection of complement activation, mPFC dysfunction, and depression and a promising therapeutic target for MDD.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102614"},"PeriodicalIF":6.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645196","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}

{"title":"Prefrontal-subthalamic theta signaling mediates delayed responses during conflict processing","authors":"Jeong Woo Choi ,&nbsp;Mahsa Malekmohammadi ,&nbsp;Soroush Niketeghad ,&nbsp;Katy A. Cross ,&nbsp;Hamasa Ebadi ,&nbsp;Amirreza Alijanpourotaghsara ,&nbsp;Adam Aron ,&nbsp;Ueli Rutishauser ,&nbsp;Nader Pouratian","doi":"10.1016/j.pneurobio.2024.102613","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102613","url":null,"abstract":"<div><p>While medial frontal cortex (MFC) and subthalamic nucleus (STN) have been implicated in conflict monitoring and action inhibition, respectively, an integrated understanding of the spatiotemporal and spectral interaction of these nodes and how they interact with motor cortex (M1) to definitively modify motor behavior during conflict is lacking. We recorded neural signals intracranially across presupplementary motor area (preSMA), M1, STN, and globus pallidus internus (GPi), during a flanker task in 20 patients undergoing deep brain stimulation implantation surgery for Parkinson disease or dystonia. Conflict is associated with sequential and causal increases in local theta power from preSMA to STN to M1 with movement delays directly correlated with increased STN theta power, indicating preSMA is the MFC locus that monitors conflict and signals STN to implement a ‘break.’ Transmission of theta from STN-to-M1 subsequently results in a transient increase in M1-to-GPi beta flow immediately prior to movement, modulating the motor network to actuate the conflict-related action inhibition (i.e., delayed response). Action regulation during conflict relies on two distinct circuits, the conflict-related theta and movement-related beta networks, that are separated spatially, spectrally, and temporally, but which interact dynamically to mediate motor performance, highlighting complex parallel yet interacting networks regulating movement.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102613"},"PeriodicalIF":6.7,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619210","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}

{"title":"Atypical connectome topography and signal flow in temporal lobe epilepsy","authors":"Ke Xie ,&nbsp;Jessica Royer ,&nbsp;Sara Larivière ,&nbsp;Raul Rodriguez-Cruces ,&nbsp;Stefan Frässle ,&nbsp;Donna Gift Cabalo ,&nbsp;Alexander Ngo ,&nbsp;Jordan DeKraker ,&nbsp;Hans Auer ,&nbsp;Shahin Tavakol ,&nbsp;Yifei Weng ,&nbsp;Chifaou Abdallah ,&nbsp;Thaera Arafat ,&nbsp;Linda Horwood ,&nbsp;Birgit Frauscher ,&nbsp;Lorenzo Caciagli ,&nbsp;Andrea Bernasconi ,&nbsp;Neda Bernasconi ,&nbsp;Zhiqiang Zhang ,&nbsp;Luis Concha ,&nbsp;Boris C. Bernhardt","doi":"10.1016/j.pneurobio.2024.102604","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102604","url":null,"abstract":"<div><p>Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102604"},"PeriodicalIF":6.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622261","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}

{"title":"The STRAT-PARK cohort: A personalized initiative to stratify Parkinson’s disease","authors":"Kjersti Eline Stige ,&nbsp;Simon Ulvenes Kverneng ,&nbsp;Soumya Sharma ,&nbsp;Geir-Olve Skeie ,&nbsp;Erika Sheard ,&nbsp;Mona Søgnen ,&nbsp;Solveig Af Geijerstam ,&nbsp;Therese Vetås ,&nbsp;Anne Grete Wahlvåg ,&nbsp;Haakon Berven ,&nbsp;Sagar Buch ,&nbsp;David Reese ,&nbsp;Dina Babiker ,&nbsp;Yekta Mahdi ,&nbsp;Trevor Wade ,&nbsp;Gala Prado Miranda ,&nbsp;Jacky Ganguly ,&nbsp;Yokhesh Krishnasamy Tamilselvam ,&nbsp;Jia Ren Chai ,&nbsp;Saurabh Bansal ,&nbsp;Charalampos Tzoulis","doi":"10.1016/j.pneurobio.2024.102603","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102603","url":null,"abstract":"<div><p>The STRAT-PARK initiative aims to provide a platform for stratifying Parkinson’s disease (PD) into biological subtypes, using a bottom-up, multidisciplinary biomarker-based and data-driven approach. PD is a heterogeneous entity, exhibiting high interindividual clinicopathological variability. This diversity suggests that PD may encompass multiple distinct biological entities, each driven by different molecular mechanisms. Molecular stratification and identification of disease subtypes is therefore a key priority for understanding and treating PD. STRAT-PARK is a multi-center longitudinal cohort aiming to recruit a total of 2000 individuals with PD and neurologically healthy controls from Norway and Canada, for the purpose of identifying molecular disease subtypes. Clinical assessment is performed annually, whereas biosampling, imaging, and digital and neurophysiological phenotyping occur every second year. The unique feature of STRAT-PARK is the diversity of collected biological material, including muscle biopsies and platelets, tissues particularly useful for mitochondrial biomarker research. Recruitment rate is ∼150 participants per year. By March 2023, 252 participants were included, comprising 204 cases and 48 controls. STRAT-PARK is a powerful stratification initiative anticipated to become a global research resource, contributing to personalized care in PD.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102603"},"PeriodicalIF":6.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S030100822400039X/pdfft?md5=630f3f1dd52d384d33d0134b2a4afa3b&pid=1-s2.0-S030100822400039X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638313","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}

{"title":"Mixed selectivity in monkey anterior intraparietal area during visual and motor processes","authors":"Monica Maranesi,&nbsp;Marco Lanzilotto,&nbsp;Edoardo Arcuri,&nbsp;Luca Bonini","doi":"10.1016/j.pneurobio.2024.102611","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102611","url":null,"abstract":"<div><p>Classical studies suggest that the anterior intraparietal area (AIP) contributes to the encoding of specific information such as objects and actions of self and others, through a variety of neuronal classes, such as canonical, motor and mirror neurons. However, these studies typically focused on a single variable, leaving it unclear whether distinct sets of AIP neurons encode a single or multiple sources of information and how multimodal coding emerges. Here, we chronically recorded monkey AIP neurons in a variety of tasks and conditions classically employed in separate experiments. Most cells exhibited mixed selectivity for observed objects, executed actions, and observed actions, enhanced when this information came from the monkey’s peripersonal working space. In contrast with the classical view, our findings indicate that multimodal coding emerges in AIP from partially-mixed selectivity of individual neurons for a variety of information relevant for planning actions directed to both physical objects and other subjects.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102611"},"PeriodicalIF":6.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000479/pdfft?md5=595c2691d9c5fbf031e55a7f08f39ced&pid=1-s2.0-S0301008224000479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650146","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}

{"title":"Lateralization of dorsal fiber tract targeting Broca’s area concurs with language skills during development","authors":"Cornelius Eichner ,&nbsp;Philipp Berger ,&nbsp;Cheslie C. Klein ,&nbsp;Angela D. Friederici","doi":"10.1016/j.pneurobio.2024.102602","DOIUrl":"https://doi.org/10.1016/j.pneurobio.2024.102602","url":null,"abstract":"<div><p>Language is bounded to the left hemisphere in the adult brain and the functional lateralization can already be observed early during development. Here we investigate whether this is paralleled by a lateralization of the white matter structural language network. We analyze the strength and microstructural properties of language-related fiber tracts connecting temporal and frontal cortices with a separation of two dorsal tracts, one targeting the posterior Broca’s area (BA44) and one targeting the precentral gyrus (BA6). In a large sample of young children (3–6 years), we demonstrate that, in contrast to the BA6-targeting tract, the microstructural asymmetry of the BA44-targeting fiber tract significantly correlates locally with different aspects of development. While the asymmetry in its anterior segment reflects age, the asymmetry in its posterior segment is associated with the children’s language skills. These findings demonstrate a fine-grained structure-to-function mapping in the lateralized network and go beyond our current view of language-related human brain maturation.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102602"},"PeriodicalIF":6.7,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000388/pdfft?md5=fd3832405d43fae881959fdf5f1be647&pid=1-s2.0-S0301008224000388-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140540744","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}

{"title":"Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer’s disease","authors":"Orly Lazarov,&nbsp;Muskan Gupta,&nbsp;Pavan Kumar,&nbsp;Zachery Morrissey,&nbsp;Trongha Phan","doi":"10.1016/j.pneurobio.2024.102601","DOIUrl":"10.1016/j.pneurobio.2024.102601","url":null,"abstract":"<div><p>Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer’s disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review. We primarily focus on the dentate gyrus (DG) of the hippocampus, which is a key area of episodic memory formation. Episodic memory is significantly impaired in AD, and is also the site of adult hippocampal neurogenesis. Advancements in technology, especially opto- and chemogenetics, have made sophisticated manipulations of engram cells possible. Furthermore, innovative methods have emerged for monitoring neurons, even specific neuronal populations, <em>in vivo</em> while animals engage in tasks, such as calcium imaging. <em>In vivo</em> calcium imaging contributes to a more comprehensive understanding of engram cells. Critically, studies of the engram in the DG using these technologies have shown the important contribution of hippocampal neurogenesis for memory in both health and AD. Together, the discussion of these topics provides a holistic perspective that motivates questions for future research.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"236 ","pages":"Article 102601"},"PeriodicalIF":6.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000376/pdfft?md5=bbd721eb949c6877bee74e2d0da462e3&pid=1-s2.0-S0301008224000376-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140356409","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}

{"title":"Optogenetic and chemogenetic approaches for modeling neurological disorders in vivo","authors":"Viktoriya G. Krut’ ,&nbsp;Andrei L. Kalinichenko ,&nbsp;Dmitry I. Maltsev ,&nbsp;David Jappy ,&nbsp;Evgeny K. Shevchenko ,&nbsp;Oleg V. Podgorny ,&nbsp;Vsevolod V. Belousov","doi":"10.1016/j.pneurobio.2024.102600","DOIUrl":"10.1016/j.pneurobio.2024.102600","url":null,"abstract":"<div><p>Animal models of human neurological disorders provide valuable experimental tools which enable us to study various aspects of disorder pathogeneses, ranging from structural abnormalities and disrupted metabolism and signaling to motor and mental deficits, and allow us to test novel therapies in preclinical studies. To be valid, these animal models should recapitulate complex pathological features at the molecular, cellular, tissue, and behavioral levels as closely as possible to those observed in human subjects. Pathological states resembling known human neurological disorders can be induced in animal species by toxins, genetic factors, lesioning, or exposure to extreme conditions. In recent years, novel animal models recapitulating neuropathologies in humans have been introduced. These animal models are based on synthetic biology approaches: opto- and chemogenetics. In this paper, we review recent opto- and chemogenetics-based animal models of human neurological disorders. These models allow for the creation of pathological states by disrupting specific processes at the cellular level. The artificial pathological states mimic a range of human neurological disorders, such as aging-related dementia, Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, epilepsy, and ataxias. Opto- and chemogenetics provide new opportunities unavailable with other animal models of human neurological disorders. These techniques enable researchers to induce neuropathological states varying in severity and ranging from acute to chronic. We also discuss future directions for the development and application of synthetic biology approaches for modeling neurological disorders.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102600"},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319108","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}

{"title":"Dissecting gene expression networks in the developing hippocampus through the lens of NEIL3 depletion","authors":"Anna M. Bugaj ,&nbsp;Nicolas Kunath ,&nbsp;Vidar Langseth Saasen ,&nbsp;Marion S. Fernandez-Berrocal ,&nbsp;Ana Vankova ,&nbsp;Pål Sætrom ,&nbsp;Magnar Bjørås ,&nbsp;Jing Ye","doi":"10.1016/j.pneurobio.2024.102599","DOIUrl":"10.1016/j.pneurobio.2024.102599","url":null,"abstract":"<div><p>Gene regulation in the hippocampus is fundamental for its development, synaptic plasticity, memory formation, and adaptability. Comparisons of gene expression among different developmental stages, distinct cell types, and specific experimental conditions have identified differentially expressed genes contributing to the organization and functionality of hippocampal circuits. The NEIL3 DNA glycosylase, one of the DNA repair enzymes, plays an important role in hippocampal maturation and neuron functionality by shaping transcription. While differential gene expression (DGE) analysis has identified key genes involved, broader gene expression patterns crucial for high-order hippocampal functions remain uncharted. By utilizing the weighted gene co-expression network analysis (WGCNA), we mapped gene expression networks in immature (p8-neonatal) and mature (3 m-adult) hippocampal circuits in wild-type and NEIL3-deficient mice. Our study unveiled intricate gene network structures underlying hippocampal maturation, delineated modules of co-expressed genes, and pinpointed highly interconnected hub genes specific to the maturity of hippocampal subregions. We investigated variations within distinct gene network modules following NEIL3 depletion, uncovering NEIL3-targeted hub genes that influence module connectivity and specificity. By integrating WGCNA with DGE, we delve deeper into the NEIL3-dependent molecular intricacies of hippocampal maturation. This study provides a comprehensive systems-level analysis for assessing the potential correlation between gene connectivity and functional connectivity within the hippocampal network, thus shaping hippocampal function throughout development.</p></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"235 ","pages":"Article 102599"},"PeriodicalIF":6.7,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0301008224000352/pdfft?md5=f074a4b50d71eed55161043625d984cc&pid=1-s2.0-S0301008224000352-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207480","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}