eLife最新文献_第9页

Supralinear dendritic integration in murine dendrite-targeting interneurons.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-31 DOI: 10.7554/eLife.100268

Simonas Griesius, Amy Richardson, Dimitri Michael Kullmann

{"title":"Supralinear dendritic integration in murine dendrite-targeting interneurons.","authors":"Simonas Griesius, Amy Richardson, Dimitri Michael Kullmann","doi":"10.7554/eLife.100268","DOIUrl":"10.7554/eLife.100268","url":null,"abstract":"Non-linear summation of synaptic inputs to the dendrites of pyramidal neurons has been proposed to increase the computation capacity of neurons through coincidence detection, signal amplification, and additional logic operations such as XOR. Supralinear dendritic integration has been documented extensively in principal neurons, mediated by several voltage-dependent conductances. It has also been reported in parvalbumin-positive hippocampal basket cells, in dendrites innervated by feedback excitatory synapses. Whether other interneurons, which support feed-forward or feedback inhibition of principal neuron dendrites, also exhibit local non-linear integration of synaptic excitation is not known. Here, we use patch-clamp electrophysiology, and two-photon calcium imaging and glutamate uncaging, to show that supralinear dendritic integration of near-synchronous spatially clustered glutamate-receptor mediated depolarization occurs in NDNF-positive neurogliaform cells and oriens-lacunosum moleculare interneurons in the mouse hippocampus. Supralinear summation was detected via recordings of somatic depolarizations elicited by uncaging of glutamate on dendritic fragments, and, in neurogliaform cells, by concurrent imaging of dendritic calcium transients. Supralinearity was abolished by blocking NMDA receptors (NMDARs) but resisted blockade of voltage-gated sodium channels. Blocking L-type calcium channels abolished supralinear calcium signalling but only had a minor effect on voltage supralinearity. Dendritic boosting of spatially clustered synaptic signals argues for previously unappreciated computational complexity in dendrite-projecting inhibitory cells of the hippocampus.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-30 DOI: 10.7554/eLife.98358

Shun Hiramatsu, Kokoro Saito, Shu Kondo, Hidetaka Katow, Nobuhiro Yamagata, Chun-Fang Wu, Hiromu Tanimoto

{"title":"Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons.","authors":"Shun Hiramatsu, Kokoro Saito, Shu Kondo, Hidetaka Katow, Nobuhiro Yamagata, Chun-Fang Wu, Hiromu Tanimoto","doi":"10.7554/eLife.98358","DOIUrl":"10.7554/eLife.98358","url":null,"abstract":"Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the protocerebral anterior medial (PAM) and posterior lateral 1 (PPL1) clusters, two distinct subsets of dopamine neurons, suggesting their roles in regulating appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","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 hierarchical pathway for assembly of the distal appendages that organize primary cilia.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-30 DOI: 10.7554/eLife.85999

Tomoharu Kanie, Beibei Liu, Julia F Love, Saxton D Fisher, Anna-Karin Gustavsson, Peter K Jackson

{"title":"A hierarchical pathway for assembly of the distal appendages that organize primary cilia.","authors":"Tomoharu Kanie, Beibei Liu, Julia F Love, Saxton D Fisher, Anna-Karin Gustavsson, Peter K Jackson","doi":"10.7554/eLife.85999","DOIUrl":"10.7554/eLife.85999","url":null,"abstract":"Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for formation of the primary cilium, by regulating at least four critical steps: ciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood. Here we comprehensively analyze known and newly discovered distal appendage proteins (CEP83, SCLT1, CEP164, TTBK2, FBF1, CEP89, KIZ, ANKRD26, PIDD1, LRRC45, NCS1, CEP15) for their precise localization, order of recruitment, and their roles in each step of cilia formation. Using CRISPR-Cas9 knockouts, we show that the order of the recruitment of the distal appendage proteins is highly interconnected and a more complex hierarchy. Our analysis highlights two protein modules, CEP83-SCLT1 and CEP164-TTBK2, as critical for structural assembly of distal appendages. Functional assays revealed that CEP89 selectively functions in RAB34+ ciliary vesicle recruitment, while deletion of the integral components, CEP83-SCLT1-CEP164-TTBK2, severely compromised all four steps of cilium formation. Collectively, our analyses provide a more comprehensive view of the organization and the function of the distal appendage, paving the way for molecular understanding of ciliary assembly.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myristoylated Neuronal Calcium Sensor-1 captures the ciliary vesicle at distal appendages.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-30 DOI: 10.7554/eLife.85998

Tomoharu Kanie, Roy Ng, Keene L Abbott, Niaj Mohammad Tanvir, Esben Lorentzen, Olaf Pongs, Peter K Jackson

{"title":"Myristoylated Neuronal Calcium Sensor-1 captures the ciliary vesicle at distal appendages.","authors":"Tomoharu Kanie, Roy Ng, Keene L Abbott, Niaj Mohammad Tanvir, Esben Lorentzen, Olaf Pongs, Peter K Jackson","doi":"10.7554/eLife.85998","DOIUrl":"10.7554/eLife.85998","url":null,"abstract":"The primary cilium is a microtubule-based organelle that cycles through assembly and disassembly. In many cell types, formation of the cilium is initiated by recruitment of ciliary vesicles to the distal appendage of the mother centriole. However, the distal appendage mechanism that directly captures ciliary vesicles is yet to be identified. In an accompanying paper, we show that the distal appendage protein, CEP89, is important for the ciliary vesicle recruitment, but not for other steps of cilium formation (Tomoharu Kanie, Love, Fisher, Gustavsson, & Jackson, 2023). The lack of a membrane binding motif in CEP89 suggests that it may indirectly recruit ciliary vesicles via another binding partner. Here, we identify Neuronal Calcium Sensor-1 (NCS1) as a stoichiometric interactor of CEP89. NCS1 localizes to the position between CEP89 and a ciliary vesicle marker, RAB34, at the distal appendage. This localization was completely abolished in CEP89 knockouts, suggesting that CEP89 recruits NCS1 to the distal appendage. Similarly to CEP89 knockouts, ciliary vesicle recruitment as well as subsequent cilium formation was perturbed in NCS1 knockout cells. The ability of NCS1 to recruit the ciliary vesicle is dependent on its myristoylation motif and NCS1 knockout cells expressing a myristoylation defective mutant failed to rescue the vesicle recruitment defect despite localizing properly to the centriole. In sum, our analysis reveals the first known mechanism for how the distal appendage recruits the ciliary vesicles.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"14 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Volume electron microscopy reveals unique laminar synaptic characteristics in the human entorhinal cortex.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-30 DOI: 10.7554/eLife.96144

Sergio Plaza-Alonso, Nicolas Cano-Astorga, Javier DeFelipe, Lidia Alonso-Nanclares

引用次数: 0

Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-29 DOI: 10.7554/eLife.100525

Hendrik Heinbockel, Gregor Leicht, Anthony D Wagner, Lars Schwabe

{"title":"Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation.","authors":"Hendrik Heinbockel, Gregor Leicht, Anthony D Wagner, Lars Schwabe","doi":"10.7554/eLife.100525","DOIUrl":"10.7554/eLife.100525","url":null,"abstract":"When retrieved, seemingly stable memories can become sensitive to significant events, such as acute stress. The mechanisms underlying these memory dynamics remain poorly understood. Here, we show that noradrenergic stimulation after memory retrieval impairs subsequent remembering, depending on hippocampal and cortical signals emerging during retrieval. In a three-day study, we measured brain activity using fMRI during initial encoding, 24 hr-delayed memory cueing followed by pharmacological elevations of glucocorticoid or noradrenergic activity, and final recall. While post-retrieval glucocorticoids did not affect subsequent memory, the impairing effect of noradrenergic arousal on final recall depended on hippocampal reactivation and category-level reinstatement in the ventral temporal cortex during memory cueing. These effects did not require a reactivation of the original memory trace and did not interact with offline reinstatement during rest. Our findings demonstrate that, depending on the retrieval-related neural reactivation of memories, noradrenergic arousal after retrieval can alter the future accessibility of consolidated memories.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The multifaceted role of the inferior colliculus in sensory prediction, reward processing, and decision-making.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-29 DOI: 10.7554/eLife.101142

Xinyu Du, Haoxuan Xu, Peirun Song, Yuying Zhai, Hangting Ye, Xuehui Bao, Qianyue Huang, Hisashi Tanigawa, Zhiyi Tu, Pei Chen, Xuan Zhao, Josef P Rauschecker, Xiongjie Yu

{"title":"The multifaceted role of the inferior colliculus in sensory prediction, reward processing, and decision-making.","authors":"Xinyu Du, Haoxuan Xu, Peirun Song, Yuying Zhai, Hangting Ye, Xuehui Bao, Qianyue Huang, Hisashi Tanigawa, Zhiyi Tu, Pei Chen, Xuan Zhao, Josef P Rauschecker, Xiongjie Yu","doi":"10.7554/eLife.101142","DOIUrl":"10.7554/eLife.101142","url":null,"abstract":"The inferior colliculus (IC) has traditionally been regarded as an important relay in the auditory pathway, primarily involved in relaying auditory information from the brainstem to the thalamus. However, this study uncovers the multifaceted role of the IC in bridging auditory processing, sensory prediction, and reward prediction. Through extracellular recordings in monkeys engaged in a sound duration-based deviation detection task, we observed a 'climbing effect' in neuronal firing rates, indicative of an enhanced response over sound sequences linked to sensory prediction rather than reward anticipation. Moreover, our findings demonstrate reward prediction errors within the IC, highlighting its complex integration in auditory and reward processing. Further analysis revealed a direct correlation between IC neuronal activity and behavioral choices, suggesting its involvement in decision-making processes. This research highlights a more complex role for the IC than traditionally understood, showcasing its integral role in cognitive and sensory processing and emphasizing its importance in integrated brain functions.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

PEBP1 amplifies mitochondrial dysfunction-induced integrated stress response.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-29 DOI: 10.7554/eLife.102852

Ling Cheng, Ian Meliala, Yidi Kong, Jingyuan Chen, Christopher G Proud, Mikael Björklund

{"title":"PEBP1 amplifies mitochondrial dysfunction-induced integrated stress response.","authors":"Ling Cheng, Ian Meliala, Yidi Kong, Jingyuan Chen, Christopher G Proud, Mikael Björklund","doi":"10.7554/eLife.102852","DOIUrl":"10.7554/eLife.102852","url":null,"abstract":"Mitochondrial dysfunction is involved in numerous diseases and the aging process. The integrated stress response (ISR) serves as a critical adaptation mechanism to a variety of stresses, including those originating from mitochondria. By utilizing mass spectrometry-based cellular thermal shift assay (MS-CETSA), we uncovered that phosphatidylethanolamine-binding protein 1 (PEBP1), also known as Raf kinase inhibitory protein (RKIP), is thermally stabilized by stresses which induce mitochondrial ISR. Depletion of PEBP1 impaired mitochondrial ISR activation by reducing eukaryotic translation initiation factor 2α (eIF2α) phosphorylation and subsequent ISR gene expression, which was independent of PEBP1's role in inhibiting the RAF/MEK/ERK pathway. Consistently, overexpression of PEBP1 potentiated ISR activation by heme-regulated inhibitor (HRI) kinase, the principal eIF2α kinase in the mitochondrial ISR pathway. Real-time interaction analysis using luminescence complementation in live cells revealed an interaction between PEBP1 and eIF2α, which was disrupted by eIF2α S51 phosphorylation. These findings suggest a role for PEBP1 in amplifying mitochondrial stress signals, thereby facilitating an effective cellular response to mitochondrial dysfunction. Therefore, PEBP1 may be a potential therapeutic target for diseases associated with mitochondrial dysfunction.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

eIF3 engages with 3'-UTR termini of highly translated mRNAs.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-29 DOI: 10.7554/eLife.102977

Santi Mestre-Fos, Lucas Ferguson, Marena I Trinidad, Nicholas T Ingolia, Jamie H D Cate

{"title":"eIF3 engages with 3'-UTR termini of highly translated mRNAs.","authors":"Santi Mestre-Fos, Lucas Ferguson, Marena I Trinidad, Nicholas T Ingolia, Jamie H D Cate","doi":"10.7554/eLife.102977","DOIUrl":"10.7554/eLife.102977","url":null,"abstract":"Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3' untranslated region (3'-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3'-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3'-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling, but not with translational efficiency. The results presented here show that eIF3 engages with 3'-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Driver lines for studying associative learning in Drosophila.

IF 6.4 1区生物学

eLife Pub Date : 2025-01-29 DOI: 10.7554/eLife.94168

Yichun Shuai, Megan Sammons, Gabriella R Sterne, Karen L Hibbard, He Yang, Ching-Po Yang, Claire Managan, Igor Siwanowicz, Tzumin Lee, Gerald M Rubin, Glenn C Turner, Yoshinori Aso

{"title":"Driver lines for studying associative learning in Drosophila.","authors":"Yichun Shuai, Megan Sammons, Gabriella R Sterne, Karen L Hibbard, He Yang, Ching-Po Yang, Claire Managan, Igor Siwanowicz, Tzumin Lee, Gerald M Rubin, Glenn C Turner, Yoshinori Aso","doi":"10.7554/eLife.94168","DOIUrl":"10.7554/eLife.94168","url":null,"abstract":"The mushroom body (MB) is the center for associative learning in insects. In Drosophila, intersectional split-GAL4 drivers and electron microscopy (EM) connectomes have laid the foundation for precise interrogation of the MB neural circuits. However, investigation of many cell types upstream and downstream of the MB has been hindered due to lack of specific driver lines. Here we describe a new collection of over 800 split-GAL4 and split-LexA drivers that cover approximately 300 cell types, including sugar sensory neurons, putative nociceptive ascending neurons, olfactory and thermo-/hygro-sensory projection neurons, interneurons connected with the MB-extrinsic neurons, and various other cell types. We characterized activation phenotypes for a subset of these lines and identified a sugar sensory neuron line most suitable for reward substitution. Leveraging the thousands of confocal microscopy images associated with the collection, we analyzed neuronal morphological stereotypy and discovered that one set of mushroom body output neurons, MBON08/MBON09, exhibits striking individuality and asymmetry across animals. In conjunction with the EM connectome maps, the driver lines reported here offer a powerful resource for functional dissection of neural circuits for associative learning in adult Drosophila.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11778931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0