Pub Date : 2024-10-16DOI: 10.1523/JNEUROSCI.0575-24.2024
Yannik Stegmann, Janna Teigeler, Arash Mirifar, Andreas Keil, Matthias Gamer
When faced with danger, human beings respond with a repertoire of defensive behaviors, including freezing and active avoidance. Previous research has revealed a pattern of physiological responses, characterized by heart rate bradycardia, reduced visual exploration, and heightened sympathetic arousal in reaction to avoidable threats, suggesting a state of attentive immobility in humans. However, the electrocortical underpinnings of these behaviors remain largely unexplored. To investigate the visuocortical components of attentive immobility, we recorded parieto-occipital alpha activity, along with eye movements and autonomic responses, while participants awaited either an avoidable, inevitable, or no threat. To test the robustness and generalizability of our findings, we collected data from a total of 101 participants (76 females, 25 males) at two laboratories. Across sites, we observed an enhanced suppression of parieto-occipital alpha activity during avoidable threats, in contrast to inevitable or no threat trials, particularly toward the end of the trial that prompted avoidance responses. This response pattern coincided with heart rate bradycardia, centralization of gaze, and increased sympathetic arousal. Furthermore, our findings expand on previous research by revealing that the amount of alpha suppression, along with centralization of gaze, and heart rate changes predict the speed of motor responses. Collectively, these findings indicate that when individuals encounter avoidable threats, they enter a state of attentive immobility, which enhances perceptual processing and facilitates action preparation. This state appears to reflect freezing-like behavior in humans.
{"title":"Electrocortical Responses in Anticipation of Avoidable and Inevitable Threats: A Multisite Study.","authors":"Yannik Stegmann, Janna Teigeler, Arash Mirifar, Andreas Keil, Matthias Gamer","doi":"10.1523/JNEUROSCI.0575-24.2024","DOIUrl":"10.1523/JNEUROSCI.0575-24.2024","url":null,"abstract":"<p><p>When faced with danger, human beings respond with a repertoire of defensive behaviors, including freezing and active avoidance. Previous research has revealed a pattern of physiological responses, characterized by heart rate bradycardia, reduced visual exploration, and heightened sympathetic arousal in reaction to avoidable threats, suggesting a state of attentive immobility in humans. However, the electrocortical underpinnings of these behaviors remain largely unexplored. To investigate the visuocortical components of attentive immobility, we recorded parieto-occipital alpha activity, along with eye movements and autonomic responses, while participants awaited either an avoidable, inevitable, or no threat. To test the robustness and generalizability of our findings, we collected data from a total of 101 participants (76 females, 25 males) at two laboratories. Across sites, we observed an enhanced suppression of parieto-occipital alpha activity during avoidable threats, in contrast to inevitable or no threat trials, particularly toward the end of the trial that prompted avoidance responses. This response pattern coincided with heart rate bradycardia, centralization of gaze, and increased sympathetic arousal. Furthermore, our findings expand on previous research by revealing that the amount of alpha suppression, along with centralization of gaze, and heart rate changes predict the speed of motor responses. Collectively, these findings indicate that when individuals encounter avoidable threats, they enter a state of attentive immobility, which enhances perceptual processing and facilitates action preparation. This state appears to reflect freezing-like behavior in humans.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127207","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}
Pub Date : 2024-10-15DOI: 10.1523/JNEUROSCI.1734-23.2024
Farzaneh S Mirfakhar, Jorge Castanheira, Raquel Domingues, José S Ramalho, Cláudia Guimas Almeida
CD2AP was identified as a genetic risk factor for late-onset Alzheimer's disease (LOAD). However, it is unclear how CD2AP contributes to LOAD synaptic dysfunction underlying AD memory deficits. We have shown that loss of CD2AP function increases β-amyloid (Aβ) endocytic production, but it is unknown whether it contributes to synapse dysfunction. As CD2AP is an actin-binding protein, it may also function in F-actin-rich dendritic spines, which are the excitatory postsynaptic compartments. Here, we demonstrate that CD2AP colocalizes with F-actin in dendritic spines of primary mouse cortical neurons of both sexes. Cell-autonomous depletion of CD2AP specifically reduces spine density and volume, resulting in a functional decrease in synapse formation and neuronal network activity. Post-synaptic reexpression of CD2AP, but not blocking Aβ-production, is sufficient to rescue spine density. CD2AP overexpression increases spine density, volume, and synapse formation, while a rare LOAD CD2AP mutation induces aberrant F-actin spine-like protrusions without functional synapses. CD2AP controls postsynaptic actin turnover, with the LOAD mutation in CD2AP decreasing F-actin dynamicity. Our data support that CD2AP risk variants could contribute to LOAD synapse dysfunction by disrupting spine formation and growth by deregulating actin dynamics.Significance statement CD2AP is a candidate genetic risk factor of late-onset Alzheimer's disease (LOAD) expressed in neurons with an unknown impact on synapse dysfunction, one of the causal LOAD mechanisms. Our research has revealed CD2AP as a new synaptic protein and established a connection between a LOAD genetic variant in CD2AP and synaptic dysfunction independent of beta-amyloid accumulation. This study suggests an explanation for the CD2AP-mediated predisposition to AD. Furthermore, we have found that controlling CD2AP's impact on spinal F-actin could be a potential target for therapeutic intervention against LOAD.
{"title":"The Alzheimer's disease risk gene CD2AP functions in dendritic spines by remodeling F-actin.","authors":"Farzaneh S Mirfakhar, Jorge Castanheira, Raquel Domingues, José S Ramalho, Cláudia Guimas Almeida","doi":"10.1523/JNEUROSCI.1734-23.2024","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1734-23.2024","url":null,"abstract":"<p><p>CD2AP was identified as a genetic risk factor for late-onset Alzheimer's disease (LOAD). However, it is unclear how CD2AP contributes to LOAD synaptic dysfunction underlying AD memory deficits. We have shown that loss of CD2AP function increases β-amyloid (Aβ) endocytic production, but it is unknown whether it contributes to synapse dysfunction. As CD2AP is an actin-binding protein, it may also function in F-actin-rich dendritic spines, which are the excitatory postsynaptic compartments. Here, we demonstrate that CD2AP colocalizes with F-actin in dendritic spines of primary mouse cortical neurons of both sexes. Cell-autonomous depletion of CD2AP specifically reduces spine density and volume, resulting in a functional decrease in synapse formation and neuronal network activity. Post-synaptic reexpression of CD2AP, but not blocking Aβ-production, is sufficient to rescue spine density. CD2AP overexpression increases spine density, volume, and synapse formation, while a rare LOAD CD2AP mutation induces aberrant F-actin spine-like protrusions without functional synapses. CD2AP controls postsynaptic actin turnover, with the LOAD mutation in CD2AP decreasing F-actin dynamicity. Our data support that CD2AP risk variants could contribute to LOAD synapse dysfunction by disrupting spine formation and growth by deregulating actin dynamics.<b>Significance statement</b> CD2AP is a candidate genetic risk factor of late-onset Alzheimer's disease (LOAD) expressed in neurons with an unknown impact on synapse dysfunction, one of the causal LOAD mechanisms. Our research has revealed CD2AP as a new synaptic protein and established a connection between a LOAD genetic variant in CD2AP and synaptic dysfunction independent of beta-amyloid accumulation. This study suggests an explanation for the CD2AP-mediated predisposition to AD. Furthermore, we have found that controlling CD2AP's impact on spinal F-actin could be a potential target for therapeutic intervention against LOAD.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479407","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}
Spike timing-dependent plasticity (STDP) is a learning rule important for synaptic refinement and for learning and memory during development. While different forms of presynaptic t-LTD have been deeply investigated, little is known about the mechanisms of somatosensory cortex postsynaptic t-LTD. In the present work, we investigated the requirements and mechanisms for induction of developmental spike timing-dependent long-term depression (t-LTD) at L2/3-L2/3 synapses in the juvenile mouse somatosensory cortex. We found that P13-21 mice of either sex show t-LTD at L2/3-L2/3 synapses induced by pairing single presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz) is expressed postsynaptically, and requires the activation of ionotropic postsynaptic NMDA-type glutamate receptors containing GluN2B subunits. In addition, it requires postsynaptic Ca2+, Ca2+ release from internal stores, calcineurin, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signalling to release the gliotransmitter d-serine to activate postsynaptic NMDARs to induce t-LTD. These results show direct evidence of the mechanism involved in developmental postsynaptic t-LTD at L2/3-L2/3 synapses, revealing a central role of astrocytes and their release of D-serine in its induction.Significance statement We show here the mechanisms and role of astrocytes and gliotransmitters in a postsynaptic spike timing dependent long-term depression (t-LTD) form defined at layer (L)2/3-L2/3 synapses of the somatosensory cortex. We have discovered that this form of plasticity involves N-methyl D-aspartate receptors (NMDAR) containing the GluN2B subunit and requires astrocytes and the gliotransmitter D-serine to co-activate (together with glutamate) postsynaptic NMDAR to mediate LTD. This can be a general mechanism in the brain to define different forms of plasticity. Defining the mechanisms of synaptic plasticity may have important implications for brain repair, sensorial recovery, the treatment of neurodevelopmental disorders and even, for educational policy.
{"title":"Developmental spike timing-dependent long-term depression requires astrocyte D-serine at L2/3-L2/3 synapses of the mouse somatosensory cortex.","authors":"Yuniesky Andrade-Talavera,Joaquín Sánchez-Gómez,Heriberto Coatl-Cuaya,Antonio Rodríguez-Moreno","doi":"10.1523/jneurosci.0805-24.2024","DOIUrl":"https://doi.org/10.1523/jneurosci.0805-24.2024","url":null,"abstract":"Spike timing-dependent plasticity (STDP) is a learning rule important for synaptic refinement and for learning and memory during development. While different forms of presynaptic t-LTD have been deeply investigated, little is known about the mechanisms of somatosensory cortex postsynaptic t-LTD. In the present work, we investigated the requirements and mechanisms for induction of developmental spike timing-dependent long-term depression (t-LTD) at L2/3-L2/3 synapses in the juvenile mouse somatosensory cortex. We found that P13-21 mice of either sex show t-LTD at L2/3-L2/3 synapses induced by pairing single presynaptic activity with single postsynaptic action potentials at low stimulation frequency (0.2 Hz) is expressed postsynaptically, and requires the activation of ionotropic postsynaptic NMDA-type glutamate receptors containing GluN2B subunits. In addition, it requires postsynaptic Ca2+, Ca2+ release from internal stores, calcineurin, postsynaptic endocannabinoid (eCB) synthesis, activation of CB1 receptors and astrocytic signalling to release the gliotransmitter d-serine to activate postsynaptic NMDARs to induce t-LTD. These results show direct evidence of the mechanism involved in developmental postsynaptic t-LTD at L2/3-L2/3 synapses, revealing a central role of astrocytes and their release of D-serine in its induction.Significance statement We show here the mechanisms and role of astrocytes and gliotransmitters in a postsynaptic spike timing dependent long-term depression (t-LTD) form defined at layer (L)2/3-L2/3 synapses of the somatosensory cortex. We have discovered that this form of plasticity involves N-methyl D-aspartate receptors (NMDAR) containing the GluN2B subunit and requires astrocytes and the gliotransmitter D-serine to co-activate (together with glutamate) postsynaptic NMDAR to mediate LTD. This can be a general mechanism in the brain to define different forms of plasticity. Defining the mechanisms of synaptic plasticity may have important implications for brain repair, sensorial recovery, the treatment of neurodevelopmental disorders and even, for educational policy.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443704","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}
Pub Date : 2024-10-15DOI: 10.1523/jneurosci.1482-23.2024
Michael Alasoadura,Juliette Leclerc,Mahmoud Hazime,Jérôme Leprince,David Vaudry,Julien Chuquet
The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex, harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates, remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the peri-infarct cortex prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the peri-infarct cortex of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30-50 Hz) precisely during the critical time window for recovery (1 to 3 weeks after stroke). The collapse of L-gamma power negatively corelated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the peri-infarct cortex revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the peri-infarct cortex. Altogether the present data point-out that the chronic excess of ambient GABA in the peri-infarct cortex limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.Significance Statement After a stroke, the recovery of lost motor function depends on the reorganization of surviving neural networks. However, the excitation/inhibition balance in the repairing area is suboptimal as it leans excessively towards inhibition. In this work, using an in vivo approach, we demonstrate here that this imbalance, occurring during the critical window for recovery, leads to the collapse of gamma oscillations, a crucial cerebral rhythm for organizing neural communication. This study reinforces the concept of timely therapeutic interventions aimed at correcting the pathological oscillatory regimen of stroke recovery to enhance plasticity.
{"title":"The excessive tonic inhibition of the peri-infarct cortex depresses low gamma rhythm power during post-stroke recovery.","authors":"Michael Alasoadura,Juliette Leclerc,Mahmoud Hazime,Jérôme Leprince,David Vaudry,Julien Chuquet","doi":"10.1523/jneurosci.1482-23.2024","DOIUrl":"https://doi.org/10.1523/jneurosci.1482-23.2024","url":null,"abstract":"The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex, harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates, remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the peri-infarct cortex prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the peri-infarct cortex of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30-50 Hz) precisely during the critical time window for recovery (1 to 3 weeks after stroke). The collapse of L-gamma power negatively corelated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the peri-infarct cortex revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the peri-infarct cortex. Altogether the present data point-out that the chronic excess of ambient GABA in the peri-infarct cortex limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.Significance Statement After a stroke, the recovery of lost motor function depends on the reorganization of surviving neural networks. However, the excitation/inhibition balance in the repairing area is suboptimal as it leans excessively towards inhibition. In this work, using an in vivo approach, we demonstrate here that this imbalance, occurring during the critical window for recovery, leads to the collapse of gamma oscillations, a crucial cerebral rhythm for organizing neural communication. This study reinforces the concept of timely therapeutic interventions aimed at correcting the pathological oscillatory regimen of stroke recovery to enhance plasticity.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443703","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}
Pub Date : 2024-10-15DOI: 10.1523/jneurosci.0946-24.2024
Vidya Jadhav,Maria Isabel Carreno-Munoz,Pegah Chehrazi,Jacques L Michaud,Bidisha Chattopadhyaya,Graziella Di Cristo
Mutations in SYNGAP1, a protein enriched at glutamatergic synapses, cause intellectual disability associated with epilepsy, autism spectrum disorder and sensory dysfunctions. Several studies showed that Syngap1 regulates the time course of forebrain glutamatergic synapse maturation; however, the developmental role of Syngap1 in inhibitory GABAergic neurons is less clear. GABAergic neurons can be classified into different subtypes based on their morphology, connectivity and physiological properties. Whether Syngap1 expression specifically in Parvalbumin (PV) and Somatostatin (SST)-expressing interneurons, which are derived from the medial ganglionic eminence, plays a role in the emergence of distinct brain functions remains largely unknown. We used genetic strategies to generate Syngap1 haploinsufficiency in a) prenatal interneurons derived from the medial ganglionic eminence, b) in postnatal PV cells and c) in prenatal SST interneurons. We further performed in vivo recordings and behavioral assays to test whether and how these different genetic manipulations alter brain function and behavior in mice of either sex.Mice with prenatal-onset Syngap1 haploinsufficiency restricted to Nkx2.1-expressing neurons show abnormal cortical oscillations and increased entrainment induced by 40Hz auditory stimulation, but lack of stimulus-specific adaptation. This latter phenotype was reproduced in mice with Syngap1 haploinsufficiency restricted to PV, but not SST, interneurons. Prenatal-onset Syngap1 haploinsufficiency in Nkx2.1-expressing neurons led to impaired social behavior and inability to extinguish fear memories; however, neither postnatal PV- nor prenatal SST-specific mutant mice show these phenotypes. We speculate that Syngap1 haploinsufficiency in prenatal/perinatal PV interneurons may contribute to cortical activity and cognitive alterations associated with Syngap1 mutations.Significance statement Mutations in the human gene cause a form of developmental epileptic encephalopathy associated with intellectual disability, autism and sensory dysfunctions. Several studies have shown that in addition to playing a major role in the synaptic maturation and plasticity of forebrain excitatory neurons, Syngap1 affects GABAergic circuit function as well. Forebrain GABAergic neurons can be divided into different subtypes. Whether Syngap1 expression specifically in distinct interneuron populations and during specific developmental time windows plays a role in the emergence of distinct brain functions remains largely unknown. Here, we report that early, pre or perinatal Syngap1 expression in developing GABAergic neurons derived from the medial ganglionic eminence promotes the development of auditory cortex function, social behavior and ability to extinguish fear memories.
{"title":"Developmental Syngap1 haploinsufficiency in medial ganglionic eminence-derived interneurons impairs auditory cortex activity, social behavior and extinction of fear memory.","authors":"Vidya Jadhav,Maria Isabel Carreno-Munoz,Pegah Chehrazi,Jacques L Michaud,Bidisha Chattopadhyaya,Graziella Di Cristo","doi":"10.1523/jneurosci.0946-24.2024","DOIUrl":"https://doi.org/10.1523/jneurosci.0946-24.2024","url":null,"abstract":"Mutations in SYNGAP1, a protein enriched at glutamatergic synapses, cause intellectual disability associated with epilepsy, autism spectrum disorder and sensory dysfunctions. Several studies showed that Syngap1 regulates the time course of forebrain glutamatergic synapse maturation; however, the developmental role of Syngap1 in inhibitory GABAergic neurons is less clear. GABAergic neurons can be classified into different subtypes based on their morphology, connectivity and physiological properties. Whether Syngap1 expression specifically in Parvalbumin (PV) and Somatostatin (SST)-expressing interneurons, which are derived from the medial ganglionic eminence, plays a role in the emergence of distinct brain functions remains largely unknown. We used genetic strategies to generate Syngap1 haploinsufficiency in a) prenatal interneurons derived from the medial ganglionic eminence, b) in postnatal PV cells and c) in prenatal SST interneurons. We further performed in vivo recordings and behavioral assays to test whether and how these different genetic manipulations alter brain function and behavior in mice of either sex.Mice with prenatal-onset Syngap1 haploinsufficiency restricted to Nkx2.1-expressing neurons show abnormal cortical oscillations and increased entrainment induced by 40Hz auditory stimulation, but lack of stimulus-specific adaptation. This latter phenotype was reproduced in mice with Syngap1 haploinsufficiency restricted to PV, but not SST, interneurons. Prenatal-onset Syngap1 haploinsufficiency in Nkx2.1-expressing neurons led to impaired social behavior and inability to extinguish fear memories; however, neither postnatal PV- nor prenatal SST-specific mutant mice show these phenotypes. We speculate that Syngap1 haploinsufficiency in prenatal/perinatal PV interneurons may contribute to cortical activity and cognitive alterations associated with Syngap1 mutations.Significance statement Mutations in the human gene cause a form of developmental epileptic encephalopathy associated with intellectual disability, autism and sensory dysfunctions. Several studies have shown that in addition to playing a major role in the synaptic maturation and plasticity of forebrain excitatory neurons, Syngap1 affects GABAergic circuit function as well. Forebrain GABAergic neurons can be divided into different subtypes. Whether Syngap1 expression specifically in distinct interneuron populations and during specific developmental time windows plays a role in the emergence of distinct brain functions remains largely unknown. Here, we report that early, pre or perinatal Syngap1 expression in developing GABAergic neurons derived from the medial ganglionic eminence promotes the development of auditory cortex function, social behavior and ability to extinguish fear memories.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443706","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}
Pub Date : 2024-10-15DOI: 10.1523/jneurosci.0892-24.2024
Motoaki Uchimura,Hironori Kumano,Shigeru Kitazawa
Visual information is initially represented in retinotopic coordinates and later in craniotopic coordinates. Psychophysical evidence suggests that visual information is further represented in more general coordinates related to the external world; however, the neural basis of non-egocentric coordinates remains elusive. This study investigates the automatic transformation from egocentric to non-egocentric coordinates in the macaque precuneus (two males, one female), identified by a functional imaging study as a key area for non-egocentric representation. We found that 6.2% of neurons in the precuneus have receptive fields anchored to the background rather than to the retina or the head, while 16% had traditional retinotopic receptive fields. Notably, these two types were not exclusive: many background-centric neurons initially encode a stimulus's position in retinotopic coordinates (up to ∼90 ms from stimulus onset) but later shift to background coordinates, peaking at ∼150 ms. Regarding retinotopic information, the stimulus dominated the initial period, whereas the background dominated the later period. In the absence of a background, there is a dramatic surge in retinotopic information about the stimulus during the later phase, clearly delineating two distinct periods of retinotopic encoding: one focusing on the figure to be attended and another on the background. These findings suggest that the initial retinotopic information of the stimulus is combined with the background retinotopic information in a subsequent stage, yielding a more stable representation of the stimulus relative to the background through time-division multiplexing.Significance Statement According to psychological literature, the location of visual stimuli is automatically positioned against the background of a scene. This representation relative to the background, not being influenced by eye movements, should be important for stabilizing the visual world. A human functional imaging study suggested that the precuneus in the medial cerebral cortex is a strong candidate. This study recorded neural activity from the precuneus of monkeys and demonstrated the existence of background-centered cells with receptive fields fixed relative to the background.
{"title":"Neural Transformation from Retinotopic to Background-Centric Coordinates in the Macaque Precuneus.","authors":"Motoaki Uchimura,Hironori Kumano,Shigeru Kitazawa","doi":"10.1523/jneurosci.0892-24.2024","DOIUrl":"https://doi.org/10.1523/jneurosci.0892-24.2024","url":null,"abstract":"Visual information is initially represented in retinotopic coordinates and later in craniotopic coordinates. Psychophysical evidence suggests that visual information is further represented in more general coordinates related to the external world; however, the neural basis of non-egocentric coordinates remains elusive. This study investigates the automatic transformation from egocentric to non-egocentric coordinates in the macaque precuneus (two males, one female), identified by a functional imaging study as a key area for non-egocentric representation. We found that 6.2% of neurons in the precuneus have receptive fields anchored to the background rather than to the retina or the head, while 16% had traditional retinotopic receptive fields. Notably, these two types were not exclusive: many background-centric neurons initially encode a stimulus's position in retinotopic coordinates (up to ∼90 ms from stimulus onset) but later shift to background coordinates, peaking at ∼150 ms. Regarding retinotopic information, the stimulus dominated the initial period, whereas the background dominated the later period. In the absence of a background, there is a dramatic surge in retinotopic information about the stimulus during the later phase, clearly delineating two distinct periods of retinotopic encoding: one focusing on the figure to be attended and another on the background. These findings suggest that the initial retinotopic information of the stimulus is combined with the background retinotopic information in a subsequent stage, yielding a more stable representation of the stimulus relative to the background through time-division multiplexing.Significance Statement According to psychological literature, the location of visual stimuli is automatically positioned against the background of a scene. This representation relative to the background, not being influenced by eye movements, should be important for stabilizing the visual world. A human functional imaging study suggested that the precuneus in the medial cerebral cortex is a strong candidate. This study recorded neural activity from the precuneus of monkeys and demonstrated the existence of background-centered cells with receptive fields fixed relative to the background.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443705","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}
Brain oscillations in the alpha-band (8-14Hz) over posterior areas have been linked to specific processes in attention and perception. In particular, decreases in alpha-amplitude are thought to reflect activation of perceptually relevant brain areas for target engagement, while increases in alpha-amplitude have been associated with inhibition for distractor suppression. Traditionally, these alpha-changes have been viewed as two facets of the same process. However, more recent evidence calls for revisiting this interpretation. Here, we concurrently recorded MEG/EEG in 32 participants (19 females) during covert visuo-spatial attention shifts (spatial cues), and two control conditions (neutral cue, no-attention cue), while tracking fixational eye-movements. In disagreement with a single, perceptually relevant alpha-process, we found the typical alpha-modulations contra- and ipsilateral to the attention focus to be triple dissociated in their timing, topography, and spectral features: Ipsilateral alpha-increases occurred early, over occipital sensors, at a high alpha-frequency (10-14Hz) and were expressed during spatial attention (alpha spatial cue > neutral cue). By contrast, contralateral alpha-decreases occurred later, over parietal sensors, at a lower alpha-frequency (7-10Hz) and were associated with attention deployment in general (alpha spatial&neutral cue < no-attention cue). Additionally, the lateralized early alpha-increases but not -decreases during spatial attention coincided in time with directionally biased microsaccades. Overall, these findings suggest that the attention-related early alpha-increases and late -decreases reflect distinct, likely reflexive versus endogenously controlled attention mechanisms. We conclude that there is more than one perceptually relevant posterior alpha-oscillation, which need to be dissociated for a detailed account of their roles in perception and attention.Significance statement This study provides novel insights into perceptually relevant brain oscillations in the "canonical" alpha-band, and the neural correlates of covert and overt attention processes. This by simultaneously recording MEG and EEG, and isolating by design visuospatial and temporal expectations respectively, while tracking fixational eye-movements concurrently to the nominally covert attention shifts. The data reveal the presence of two, spatio-temporally and spectrally dissociated patterns of posterior alpha-changes that are distinctively associated with deployment of spatial and temporal anticipation, and eye-movement activity. This refines our understanding of the role of brain oscillations in perception and attention, the neural underpinnings of attention deployment in space and time, and provides methodological pointers for the study of perceptually relevant oscillatory activity through MEG/EEG.
{"title":"Oscillatory brain activity in the canonical alpha-band conceals distinct mechanisms in attention.","authors":"Gabriela Cruz,María Melcón,Leonardo Sutandi,J Matias Palva,Satu Palva,Gregor Thut","doi":"10.1523/jneurosci.0918-24.2024","DOIUrl":"https://doi.org/10.1523/jneurosci.0918-24.2024","url":null,"abstract":"Brain oscillations in the alpha-band (8-14Hz) over posterior areas have been linked to specific processes in attention and perception. In particular, decreases in alpha-amplitude are thought to reflect activation of perceptually relevant brain areas for target engagement, while increases in alpha-amplitude have been associated with inhibition for distractor suppression. Traditionally, these alpha-changes have been viewed as two facets of the same process. However, more recent evidence calls for revisiting this interpretation. Here, we concurrently recorded MEG/EEG in 32 participants (19 females) during covert visuo-spatial attention shifts (spatial cues), and two control conditions (neutral cue, no-attention cue), while tracking fixational eye-movements. In disagreement with a single, perceptually relevant alpha-process, we found the typical alpha-modulations contra- and ipsilateral to the attention focus to be triple dissociated in their timing, topography, and spectral features: Ipsilateral alpha-increases occurred early, over occipital sensors, at a high alpha-frequency (10-14Hz) and were expressed during spatial attention (alpha spatial cue > neutral cue). By contrast, contralateral alpha-decreases occurred later, over parietal sensors, at a lower alpha-frequency (7-10Hz) and were associated with attention deployment in general (alpha spatial&neutral cue < no-attention cue). Additionally, the lateralized early alpha-increases but not -decreases during spatial attention coincided in time with directionally biased microsaccades. Overall, these findings suggest that the attention-related early alpha-increases and late -decreases reflect distinct, likely reflexive versus endogenously controlled attention mechanisms. We conclude that there is more than one perceptually relevant posterior alpha-oscillation, which need to be dissociated for a detailed account of their roles in perception and attention.Significance statement This study provides novel insights into perceptually relevant brain oscillations in the \"canonical\" alpha-band, and the neural correlates of covert and overt attention processes. This by simultaneously recording MEG and EEG, and isolating by design visuospatial and temporal expectations respectively, while tracking fixational eye-movements concurrently to the nominally covert attention shifts. The data reveal the presence of two, spatio-temporally and spectrally dissociated patterns of posterior alpha-changes that are distinctively associated with deployment of spatial and temporal anticipation, and eye-movement activity. This refines our understanding of the role of brain oscillations in perception and attention, the neural underpinnings of attention deployment in space and time, and provides methodological pointers for the study of perceptually relevant oscillatory activity through MEG/EEG.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443710","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}
Pub Date : 2024-10-09DOI: 10.1523/JNEUROSCI.0591-24.2024
Elena Neumann, Teresa Cramer, Mario A Acuña, Louis Scheurer, Camilla Beccarini, Bernhard Luscher, Hendrik Wildner, Hanns Ulrich Zeilhofer
GABAergic neurons and GABAA receptors (GABAARs) are critical elements of almost all neuronal circuits. Most GABAARs of the CNS are heteropentameric ion channels composed of two α, two β, and one γ subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABAARs. Most GABAAR classifications rely on the heterogeneity of the α subunit (α1-α6) included in the receptor complex. Heterogeneity of the γ subunits (γ1-γ3), which mediate synaptic clustering of GABAARs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because γ2 subunits greatly outnumber the other γ subunits in most brain regions. Here, we have investigated a potential role of non-γ2 GABAARs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides γ2 subunits, γ1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global γ2 subunit deletion, which is lethal, spinal cord-specific loss of γ2 subunits was well tolerated. GABAAR clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of γ1 subunits that support the synaptic clustering of GABAARs in this site. They further suggest that γ1 containing GABAARs contribute to the spinal control of nociceptive information flow.
{"title":"γ1 GABA<sub>A</sub> Receptors in Spinal Nociceptive Circuits.","authors":"Elena Neumann, Teresa Cramer, Mario A Acuña, Louis Scheurer, Camilla Beccarini, Bernhard Luscher, Hendrik Wildner, Hanns Ulrich Zeilhofer","doi":"10.1523/JNEUROSCI.0591-24.2024","DOIUrl":"10.1523/JNEUROSCI.0591-24.2024","url":null,"abstract":"<p><p>GABAergic neurons and GABA<sub>A</sub> receptors (GABA<sub>A</sub>Rs) are critical elements of almost all neuronal circuits. Most GABA<sub>A</sub>Rs of the CNS are heteropentameric ion channels composed of two α, two β, and one γ subunits. These receptors serve as important drug targets for benzodiazepine (BDZ) site agonists, which potentiate the action of GABA at GABA<sub>A</sub>Rs. Most GABA<sub>A</sub>R classifications rely on the heterogeneity of the α subunit (α1-α6) included in the receptor complex. Heterogeneity of the γ subunits (γ1-γ3), which mediate synaptic clustering of GABA<sub>A</sub>Rs and contribute, together with α subunits, to the benzodiazepine (BDZ) binding site, has gained less attention, mainly because γ2 subunits greatly outnumber the other γ subunits in most brain regions. Here, we have investigated a potential role of non-γ2 GABA<sub>A</sub>Rs in neural circuits of the spinal dorsal horn, a key site of nociceptive processing. Female and male mice were studied. We demonstrate that besides γ2 subunits, γ1 subunits are significantly expressed in the spinal dorsal horn, especially in its superficial layers. Unlike global γ2 subunit deletion, which is lethal, spinal cord-specific loss of γ2 subunits was well tolerated. GABA<sub>A</sub>R clustering in the superficial dorsal horn remained largely unaffected and antihyperalgesic actions of HZ-166, a nonsedative BDZ site agonist, were partially retained. Our results thus suggest that the superficial dorsal horn harbors functionally relevant amounts of γ1 subunits that support the synaptic clustering of GABA<sub>A</sub>Rs in this site. They further suggest that γ1 containing GABA<sub>A</sub>Rs contribute to the spinal control of nociceptive information flow.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977054","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}
Pub Date : 2024-10-09DOI: 10.1523/JNEUROSCI.1031-24.2024
Linda J Hoffman, Julia M Foley, Josiah K Leong, Holly Sullivan-Toole, Blake L Elliott, Ingrid R Olson
Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared with other lobules. We discovered a mediolateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socioaffective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socioaffective regulation.
{"title":"A Virtual In Vivo Dissection and Analysis of Socioaffective Symptoms Related to Cerebellum-Midbrain Reward Circuitry in Humans.","authors":"Linda J Hoffman, Julia M Foley, Josiah K Leong, Holly Sullivan-Toole, Blake L Elliott, Ingrid R Olson","doi":"10.1523/JNEUROSCI.1031-24.2024","DOIUrl":"10.1523/JNEUROSCI.1031-24.2024","url":null,"abstract":"<p><p>Emerging research in nonhuman animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white matter connectivity in a cohort of men and women using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections between the cerebellum and VTA predominantly originate in the right cerebellar hemisphere, interposed nucleus, and paravermal cortex and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared with other lobules. We discovered a mediolateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socioaffective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socioaffective regulation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299813","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}
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