Pub Date : 2023-12-06DOI: 10.1523/jneurosci.1801-23.2023
Judy Illes
{"title":"Environmental Neuroethics for Global Neuroscience","authors":"Judy Illes","doi":"10.1523/jneurosci.1801-23.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.1801-23.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"62 37","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594932","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}
Pub Date : 2023-12-06DOI: 10.1523/jneurosci.0778-23.2023
Fari Ryan, Isaac Francos-Quijorna, Gerard Hernández-Mir, Catharine Aquino, Ralph Schlapbach, Elizabeth J. Bradbury, Samuel David
Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1day, 1 and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wildtype mice. Analyses include secondary damage, a range of transcriptome and protein analyses of inflammatory, cell death and extracellular matrix (ECM) molecules; as well as immune cell infiltration; changes in axonal sprouting and locomotor recovery. Lack of TLR4 signaling results in reduced neuronal and myelin loss; reduced activation of NF-κB and decreased expression of inflammatory cytokines and necroptotic cell death pathway at a late time point (8 weeks) after injury. TLR4 null mice also showed reduction of scar-related ECM molecules at 8 weeks after SCI, accompanied by increase in ECM molecules associated with perineuronal nets, increased sprouting of serotonergic fibers and improved locomotor recovery. These findings reveal novel effects of TLR4 signaling in chronic SCI. We show that TLR4 influences inflammation, cell death, ECM deposition at late-stage post-injury when secondary injury processes are normally considered to be over. This highlights the potential for late stage targeting of TLR4 as a potential therapy for chronic SCI.Significance StatementSpinal cord injury often results in life-long paralysis and sensory loss of the limbs. Much of the research on biological mechanisms in SCI is focused on the acute period after injury. However, most SCI patients have been living with their injuries for months or years. We now show a delayed effect of Toll-like receptor 4 (TLR4) mediated inflammation several months after injury that induces changes in cytokines, neuronal cell death and extracellular matrix deposition, and axonal sprouting that can influence functional recovery. This work addresses a question of much interest in the field of spinal cord injury and could also be of wider interest for recovery after brain trauma.
{"title":"Tlr4deletion modulates cytokine and extracellular matrix expression in chronic spinal cord injury, leading to improved secondary damage and functional recovery","authors":"Fari Ryan, Isaac Francos-Quijorna, Gerard Hernández-Mir, Catharine Aquino, Ralph Schlapbach, Elizabeth J. Bradbury, Samuel David","doi":"10.1523/jneurosci.0778-23.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.0778-23.2023","url":null,"abstract":"Toll-like receptors (TLRs) play an important role in the innate immune response after CNS injury. Although TLR4 is one of the best characterized, its role in chronic stages after spinal cord injury (SCI) is not well understood. We examined the role of TLR4 signaling in injury-induced responses at 1day, 1 and 8 weeks after spinal cord contusion injury in adult female TLR4 null and wildtype mice. Analyses include secondary damage, a range of transcriptome and protein analyses of inflammatory, cell death and extracellular matrix (ECM) molecules; as well as immune cell infiltration; changes in axonal sprouting and locomotor recovery. Lack of TLR4 signaling results in reduced neuronal and myelin loss; reduced activation of NF-κB and decreased expression of inflammatory cytokines and necroptotic cell death pathway at a late time point (8 weeks) after injury. TLR4 null mice also showed reduction of scar-related ECM molecules at 8 weeks after SCI, accompanied by increase in ECM molecules associated with perineuronal nets, increased sprouting of serotonergic fibers and improved locomotor recovery. These findings reveal novel effects of TLR4 signaling in chronic SCI. We show that TLR4 influences inflammation, cell death, ECM deposition at late-stage post-injury when secondary injury processes are normally considered to be over. This highlights the potential for late stage targeting of TLR4 as a potential therapy for chronic SCI.Significance StatementSpinal cord injury often results in life-long paralysis and sensory loss of the limbs. Much of the research on biological mechanisms in SCI is focused on the acute period after injury. However, most SCI patients have been living with their injuries for months or years. We now show a delayed effect of Toll-like receptor 4 (TLR4) mediated inflammation several months after injury that induces changes in cytokines, neuronal cell death and extracellular matrix deposition, and axonal sprouting that can influence functional recovery. This work addresses a question of much interest in the field of spinal cord injury and could also be of wider interest for recovery after brain trauma.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"63 21","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138597404","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}
Pub Date : 2023-12-05DOI: 10.1523/jneurosci.2047-23.2023
{"title":"Erratum: Palazuelos et al., “TACE/ADAM17 Is Essential for Oligodendrocyte Development and CNS Myelination”","authors":"","doi":"10.1523/jneurosci.2047-23.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.2047-23.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"121 49","pages":"8825 - 8826"},"PeriodicalIF":0.0,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138599629","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}
Pub Date : 2023-11-15DOI: 10.1523/jneurosci.twij.43.46.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.46.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.46.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"8 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136228821","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}
Pub Date : 2023-11-13DOI: 10.1523/jneurosci.0910-23.2023
Prathyusha Ravi Chander, Laura Hanson, Pavitra Chundekkad, Gautam Bhagwan Awatramani
Classic ON-OFF direction-selective ganglion cells (DSGCs) that encode the four cardinal directions were recently shown to also be orientation-selective. To clarify the mechanisms underlying orientation selectivity we employed a variety of electrophysiological, optogenetic, and gene knock-out strategies to test the relative contributions of glutamate, GABA, and acetylcholine (ACh) input that are known to drive DSGCs, in male and female mouse retinas. Extracellular spike recordings revealed that DSGCs respond preferentially to either vertical or horizontal bars, those that are perpendicular to their preferred-null motion axes. By contrast, the glutamate input to all four DSGC types measured using whole-cell patch-clamp techniques was found to be tuned along the vertical axis. Tuned glutamatergic excitation was heavily reliant on type 5A bipolar cells, which appear to be electrically coupled via connexin 36 containing gap junctions to the vertically oriented processes of wide-field amacrine cells. Vertically tuned inputs are transformed by the GABAergic/cholinergic =starburst> amacrine cells (SACs), which are critical components of the direction-selective circuit, into distinct patterns of inhibition and excitation. Feed-forward SAC inhibition appears to ‘veto’ preferred orientation glutamate excitation in dorsal/ventral (but not nasal/temporal) coding DSGCs ‘flipping’ their orientation tuning by 90 degrees, and accounts for the apparent mismatch between glutamate input tuning and the DSGC's spiking response. Together, these results reveal how two distinct synaptic motifs interact to generate complex feature selectivity, shedding light on the intricate circuitry that underlies visual processing in the retina. Significance Statement The classical work of Hubel and Wiesel (1959) demonstrated that neurons in the cat visual cortex are often selective for multiple stimulus features, such as direction and orientation. Here, we show that direction-selective ganglion cells (DSGCs) in the mouse retina are also selective for stimulus orientation, suggesting that multi-feature extraction may begin earlier in the visual system than previously envisioned. Using a combination of patch-clamp, cell-specific genetic KO, and optogenetic strategies, we show that multi-feature coding relies on distinct mechanisms in the nasal/temporal and dorsal/ventral coding DSGC.
{"title":"Neural circuits underlying multi-feature extraction in the retina","authors":"Prathyusha Ravi Chander, Laura Hanson, Pavitra Chundekkad, Gautam Bhagwan Awatramani","doi":"10.1523/jneurosci.0910-23.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.0910-23.2023","url":null,"abstract":"Classic ON-OFF direction-selective ganglion cells (DSGCs) that encode the four cardinal directions were recently shown to also be orientation-selective. To clarify the mechanisms underlying orientation selectivity we employed a variety of electrophysiological, optogenetic, and gene knock-out strategies to test the relative contributions of glutamate, GABA, and acetylcholine (ACh) input that are known to drive DSGCs, in male and female mouse retinas. Extracellular spike recordings revealed that DSGCs respond preferentially to either vertical or horizontal bars, those that are perpendicular to their preferred-null motion axes. By contrast, the glutamate input to all four DSGC types measured using whole-cell patch-clamp techniques was found to be tuned along the vertical axis. Tuned glutamatergic excitation was heavily reliant on type 5A bipolar cells, which appear to be electrically coupled via connexin 36 containing gap junctions to the vertically oriented processes of wide-field amacrine cells. Vertically tuned inputs are transformed by the GABAergic/cholinergic =starburst> amacrine cells (SACs), which are critical components of the direction-selective circuit, into distinct patterns of inhibition and excitation. Feed-forward SAC inhibition appears to ‘veto’ preferred orientation glutamate excitation in dorsal/ventral (but not nasal/temporal) coding DSGCs ‘flipping’ their orientation tuning by 90 degrees, and accounts for the apparent mismatch between glutamate input tuning and the DSGC's spiking response. Together, these results reveal how two distinct synaptic motifs interact to generate complex feature selectivity, shedding light on the intricate circuitry that underlies visual processing in the retina. Significance Statement The classical work of Hubel and Wiesel (1959) demonstrated that neurons in the cat visual cortex are often selective for multiple stimulus features, such as direction and orientation. Here, we show that direction-selective ganglion cells (DSGCs) in the mouse retina are also selective for stimulus orientation, suggesting that multi-feature extraction may begin earlier in the visual system than previously envisioned. Using a combination of patch-clamp, cell-specific genetic KO, and optogenetic strategies, we show that multi-feature coding relies on distinct mechanisms in the nasal/temporal and dorsal/ventral coding DSGC.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"38 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136282564","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}
Pub Date : 2023-11-08DOI: 10.1523/jneurosci.twij.43.45.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.45.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.45.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":" 24","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135340992","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}
Pub Date : 2023-11-01DOI: 10.1523/jneurosci.twij.43.44.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.44.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.44.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"39 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135271056","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}
Pub Date : 2023-10-25DOI: 10.1523/jneurosci.twij.43.43.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.43.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.43.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"1 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135217991","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}
Pub Date : 2023-10-18DOI: 10.1523/jneurosci.twij.43.42.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.42.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.42.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135883095","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}
Pub Date : 2023-10-11DOI: 10.1523/jneurosci.twij.43.41.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/jneurosci.twij.43.41.2023","DOIUrl":"https://doi.org/10.1523/jneurosci.twij.43.41.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136098235","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}
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