Pub Date : 2020-05-02DOI: 10.1101/2020.05.01.071852
T. Handa, Rie Harukuni, T. Fukai
The frontal cortex-basal ganglia network plays a pivotal role in adaptive goal-directed behaviors. Medial frontal cortex (MFC) encodes information about choices and outcomes into sequential activation of neural population, or neural trajectory. While MFC projects to the dorsal striatum (DS), whether DS also displays temporally coordinated activity remains unknown. We studied this question by simultaneously recording neural ensembles in the MFC and DS of rodents performing an outcome-based alternative choice task. We found that the two regions exhibited highly parallel evolution of neural trajectories, transforming choice information into outcome-related information. When the two trajectories were highly correlated, spike synchrony was task-dependently modulated in some MFC-DS neuron pairs. Our results suggest that neural trajectories concomitantly process decision-relevant information in MFC and DS with increased spike synchrony between these regions.
{"title":"Concomitant Processing of Choice and Outcome in Frontal Corticostriatal Ensembles Correlates with Performance of Rats","authors":"T. Handa, Rie Harukuni, T. Fukai","doi":"10.1101/2020.05.01.071852","DOIUrl":"https://doi.org/10.1101/2020.05.01.071852","url":null,"abstract":"The frontal cortex-basal ganglia network plays a pivotal role in adaptive goal-directed behaviors. Medial frontal cortex (MFC) encodes information about choices and outcomes into sequential activation of neural population, or neural trajectory. While MFC projects to the dorsal striatum (DS), whether DS also displays temporally coordinated activity remains unknown. We studied this question by simultaneously recording neural ensembles in the MFC and DS of rodents performing an outcome-based alternative choice task. We found that the two regions exhibited highly parallel evolution of neural trajectories, transforming choice information into outcome-related information. When the two trajectories were highly correlated, spike synchrony was task-dependently modulated in some MFC-DS neuron pairs. Our results suggest that neural trajectories concomitantly process decision-relevant information in MFC and DS with increased spike synchrony between these regions.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"44 1","pages":"4357 - 4375"},"PeriodicalIF":0.0,"publicationDate":"2020-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88284554","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 : 2020-01-29DOI: 10.1101/2020.01.29.921999
R. Bauer, G. Clowry, Marcus Kaiser
One of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multi-scale, agent-based model comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure, and suggest a novel function for apoptosis. Moreover, slightly changed gene regulatory dynamics recapitulate characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.
{"title":"Creative Destruction: A Basic Computational Model of Cortical Layer Formation","authors":"R. Bauer, G. Clowry, Marcus Kaiser","doi":"10.1101/2020.01.29.921999","DOIUrl":"https://doi.org/10.1101/2020.01.29.921999","url":null,"abstract":"One of the most characteristic properties of many vertebrate neural systems is the layered organization of different cell types. This cytoarchitecture exists in the cortex, the retina, the hippocampus and many other parts of the central nervous system. The developmental mechanisms of neural layer formation have been subject to substantial experimental efforts. Here, we provide a general computational model for cortical layer formation in 3D physical space. We show that this multi-scale, agent-based model comprising two distinct stages of apoptosis, can account for the wide range of neuronal numbers encountered in different cortical areas and species. Our results demonstrate the phenotypic richness of a basic state diagram structure, and suggest a novel function for apoptosis. Moreover, slightly changed gene regulatory dynamics recapitulate characteristic properties observed in neurodevelopmental diseases. Overall, we propose a novel computational model using gene-type rules, exhibiting many characteristics of normal and pathological cortical development.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"38 1","pages":"3237 - 3253"},"PeriodicalIF":0.0,"publicationDate":"2020-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77314026","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 : 2020-01-17DOI: 10.1101/2020.01.16.909150
M. Blesa, P. Galdi, S. Cox, G. Sullivan, D. Stoye, G. Lamb, A. Quigley, M. Thrippleton, J. Escudero, M. Bastin, Keith M. Smith, J. Boardman
The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period; assess correspondences with hierarchical complexity in adulthood; and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers, and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.
{"title":"Hierarchical Complexity of the Macro-Scale Neonatal Brain","authors":"M. Blesa, P. Galdi, S. Cox, G. Sullivan, D. Stoye, G. Lamb, A. Quigley, M. Thrippleton, J. Escudero, M. Bastin, Keith M. Smith, J. Boardman","doi":"10.1101/2020.01.16.909150","DOIUrl":"https://doi.org/10.1101/2020.01.16.909150","url":null,"abstract":"The human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period; assess correspondences with hierarchical complexity in adulthood; and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers, and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"65 1","pages":"2071 - 2084"},"PeriodicalIF":0.0,"publicationDate":"2020-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87165166","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}
Michiaki Suzuki, K. Onoe, M. Sawada, Nobuaki Takahashi, N. Higo, Y. Murata, H. Tsukada, T. Isa, H. Onoe, Y. Nishimura
Abstract In a recent study, we demonstrated that the ventral striatum (VSt) controls finger movements directly during the early recovery stage after spinal cord injury (SCI), implying that the VSt may be a part of neural substrates responsible for the recovery of dexterous finger movements. The VSt is accepted widely as a key node for motivation, but is not thought to be involved in the direct control of limb movements. Therefore, whether a causal relationship exists between the VSt and motor recovery after SCI is unknown, and the role of the VSt in the recovery of dexterous finger movements orfinger movements in general after SCI remains unclear. In the present study, functional brain imaging in a macaque model of SCI revealed a strengthened functional connectivity between motor-related areas and the VSt during the recovery process for precision grip, but not whole finger grip after SCI. Furthermore, permanent lesion of the VSt impeded the recoveryof precision grip, but not coarse grip. Thus, the VSt was needed specifically for functional recovery of dexterous finger movements. These results suggest that the VSt is the key node of the cortical reorganization required for functional recovery of finger dexterity.
{"title":"The Ventral Striatum is a Key Node for Functional Recovery of Finger Dexterity After Spinal Cord Injury in Monkeys","authors":"Michiaki Suzuki, K. Onoe, M. Sawada, Nobuaki Takahashi, N. Higo, Y. Murata, H. Tsukada, T. Isa, H. Onoe, Y. Nishimura","doi":"10.1093/cercor/bhz307","DOIUrl":"https://doi.org/10.1093/cercor/bhz307","url":null,"abstract":"Abstract In a recent study, we demonstrated that the ventral striatum (VSt) controls finger movements directly during the early recovery stage after spinal cord injury (SCI), implying that the VSt may be a part of neural substrates responsible for the recovery of dexterous finger movements. The VSt is accepted widely as a key node for motivation, but is not thought to be involved in the direct control of limb movements. Therefore, whether a causal relationship exists between the VSt and motor recovery after SCI is unknown, and the role of the VSt in the recovery of dexterous finger movements orfinger movements in general after SCI remains unclear. In the present study, functional brain imaging in a macaque model of SCI revealed a strengthened functional connectivity between motor-related areas and the VSt during the recovery process for precision grip, but not whole finger grip after SCI. Furthermore, permanent lesion of the VSt impeded the recoveryof precision grip, but not coarse grip. Thus, the VSt was needed specifically for functional recovery of dexterous finger movements. These results suggest that the VSt is the key node of the cortical reorganization required for functional recovery of finger dexterity.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"09 1","pages":"3259 - 3270"},"PeriodicalIF":0.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86120032","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}
Qinlin Yu, Yun Peng, Huiying Kang, Qinmu Peng, M. Ouyang, Michelle Slinger, D. Hu, H. Shou, Fang Fang, Hao Huang
Abstract Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0–8 years and 31 children with autistic spectrum disorder (ASD) aged 2–7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0–8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0–8 years provide reference standards for biomarker detection of neuropsychiatric disorders.
{"title":"Differential White Matter Maturation from Birth to 8 Years of Age","authors":"Qinlin Yu, Yun Peng, Huiying Kang, Qinmu Peng, M. Ouyang, Michelle Slinger, D. Hu, H. Shou, Fang Fang, Hao Huang","doi":"10.1093/cercor/bhz268","DOIUrl":"https://doi.org/10.1093/cercor/bhz268","url":null,"abstract":"Abstract Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0–8 years and 31 children with autistic spectrum disorder (ASD) aged 2–7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0–8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0–8 years provide reference standards for biomarker detection of neuropsychiatric disorders.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"61 1","pages":"2674 - 2690"},"PeriodicalIF":0.0,"publicationDate":"2019-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83681849","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}
Rebecca B Hughes, Jayde Whittingham-Dowd, Rachel E. Simmons, S. Clapcote, S. Broughton, N. Dawson
Abstract 2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/− mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic “rich club” and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic “rich club” regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/− mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.
{"title":"Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion","authors":"Rebecca B Hughes, Jayde Whittingham-Dowd, Rachel E. Simmons, S. Clapcote, S. Broughton, N. Dawson","doi":"10.1093/cercor/bhz244","DOIUrl":"https://doi.org/10.1093/cercor/bhz244","url":null,"abstract":"Abstract 2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/− mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic “rich club” and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic “rich club” regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/− mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"80 1","pages":"2358 - 2371"},"PeriodicalIF":0.0,"publicationDate":"2019-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81559490","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}
Mandy H. Paul, M. Choi, J. Schlaudraff, T. Deller, D. Del Turco
Abstract The plasticity-related protein Synaptopodin (SP) has been implicated in neuronal plasticity. SP is targeted to dendritic spines and the axon initial segment, where it organizes the endoplasmic reticulum (ER) into the spine apparatus and the cisternal organelle, respectively. Here, we report an inducible third localization of SP in the somata of activated granule cell ensembles in mouse dentate gyrus. Using immunofluorescence and fluorescence in situ hybridization, we observed a subpopulation of mature granule cells (~1–2%) exhibiting perinuclear SP protein and a strong somatic SP mRNA signal. Double immunofluorescence labeling for Arc demonstrated that ~ 75% of these somatic SP-positive cells are also Arc-positive. Placement of mice into a novel environment caused a rapid (~2–4 h) induction of Arc, SP mRNA, and SP protein in exploration-induced granule cell ensembles. Lesion experiments showed that this induction requires input from the entorhinal cortex. Somatic SP colocalized with α-Actinin2, a known binding partner of SP. Finally, ultrastructural analysis revealed SP immunoprecipitate on dense plates linking cytoplasmic and perinuclear ER cisterns; these structures were absent in granule cells of SP-deficient mice. Our data implicate SP in the formation of contextual representations in the dentate gyrus and the behaviorally induced reorganization of cytoplasmic and perinuclear ER.
{"title":"Granule Cell Ensembles in Mouse Dentate Gyrus Rapidly Upregulate the Plasticity-Related Protein Synaptopodin after Exploration Behavior","authors":"Mandy H. Paul, M. Choi, J. Schlaudraff, T. Deller, D. Del Turco","doi":"10.1093/cercor/bhz231","DOIUrl":"https://doi.org/10.1093/cercor/bhz231","url":null,"abstract":"Abstract The plasticity-related protein Synaptopodin (SP) has been implicated in neuronal plasticity. SP is targeted to dendritic spines and the axon initial segment, where it organizes the endoplasmic reticulum (ER) into the spine apparatus and the cisternal organelle, respectively. Here, we report an inducible third localization of SP in the somata of activated granule cell ensembles in mouse dentate gyrus. Using immunofluorescence and fluorescence in situ hybridization, we observed a subpopulation of mature granule cells (~1–2%) exhibiting perinuclear SP protein and a strong somatic SP mRNA signal. Double immunofluorescence labeling for Arc demonstrated that ~ 75% of these somatic SP-positive cells are also Arc-positive. Placement of mice into a novel environment caused a rapid (~2–4 h) induction of Arc, SP mRNA, and SP protein in exploration-induced granule cell ensembles. Lesion experiments showed that this induction requires input from the entorhinal cortex. Somatic SP colocalized with α-Actinin2, a known binding partner of SP. Finally, ultrastructural analysis revealed SP immunoprecipitate on dense plates linking cytoplasmic and perinuclear ER cisterns; these structures were absent in granule cells of SP-deficient mice. Our data implicate SP in the formation of contextual representations in the dentate gyrus and the behaviorally induced reorganization of cytoplasmic and perinuclear ER.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"9 1","pages":"2185 - 2198"},"PeriodicalIF":0.0,"publicationDate":"2019-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75234167","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}
E. Vezzoli, C. Calì, M. De Roo, L. Ponzoni, E. Sogne, N. Gagnon, M. Francolini, D. Braida, M. Sala, D. Muller, A. Falqui, P. Magistretti
Abstract Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.
{"title":"Ultrastructural Evidence for a Role of Astrocytes and Glycogen-Derived Lactate in Learning-Dependent Synaptic Stabilization","authors":"E. Vezzoli, C. Calì, M. De Roo, L. Ponzoni, E. Sogne, N. Gagnon, M. Francolini, D. Braida, M. Sala, D. Muller, A. Falqui, P. Magistretti","doi":"10.1093/cercor/bhz226","DOIUrl":"https://doi.org/10.1093/cercor/bhz226","url":null,"abstract":"Abstract Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"15 3 1","pages":"2114 - 2127"},"PeriodicalIF":0.0,"publicationDate":"2019-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77374903","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}
The ‘default network’ (DN) becomes active when the mind is steered internally towards self-generated thoughts but turns dormant when the mind is directed externally towards the outside world. While hypotheses have been proposed to characterise the association and dissociation between different component areas of the DN, it remains unclear how they coalesce into a unitary network and fractionate into different sub-networks. Here we identified two distinct subsystems within the DN – while both subsystems show common disinterest in externally-oriented visuospatial tasks, their functional profiles differ strikingly according to the preferred contents of thoughts, preferred modes of task requirement, and causative neural dynamics among network nodes. Specifically, one subsystem comprises key nodes of the frontotemporal semantic regions. This network shows moderate dislike to visuospatial tasks, shows proclivity for task-contexts with restraints on thoughts and responses, and prefers thoughts that are focused on other people. By contrast, the other subsystem comprises the cortical midline structure and angular gyri. This network shows strong aversion to visuospatial tasks, favours task-contexts allowing free self-generated thoughts without constraints, and prefers thoughts that are focused on self. Furthermore, causative connectivity reveals that task-contexts systematically alter the dynamics within and between subsystems, suggesting flexible adaption to situational demands. This ‘self/inward vs. others/outward’ separation within the broad DN resembles recent discoveries regarding a dyadic structure within the frontoparietal network that comprises regions controlling memories/thoughts vs. regions controlling sensory-motoric processes, and echoes burgeoning views that the brain is organised with a spectrum-like architecture along gradational changes of ‘inward vs. outward’ preferences. Significance Rather than construing the default network (DN) as ‘task-negative’ regions that passively react to off-task mind-wandering, researchers have begun to acknowledge the active role of the DN in supporting internally-directed cognition. Here we found a striking dichotomy within the DN in terms of the subsystems’ task-driven functional and connectivity profiles, extending beyond previous inferences using meta-analysis and resting-state fMRI. This dichotomy reflects a local manifestation of a macro-scale gradient representation spanning across the broad cerebral cortex. This cortical gradient increases its representational complexity, from primitive sensory and motoric processing, through lexical-semantic codes for language tasks, to abstract self-generated thoughts in task-free contexts. These findings enable a framework where the separate yet related literatures of semantic cognition and default-mode processes converge.
{"title":"Bipartite Functional Fractionation within the Default Network Supports Disparate Forms of Internally Oriented Cognition","authors":"R. Chiou, Gina F. Humphreys, M. L. Lambon Ralph","doi":"10.1101/864603","DOIUrl":"https://doi.org/10.1101/864603","url":null,"abstract":"The ‘default network’ (DN) becomes active when the mind is steered internally towards self-generated thoughts but turns dormant when the mind is directed externally towards the outside world. While hypotheses have been proposed to characterise the association and dissociation between different component areas of the DN, it remains unclear how they coalesce into a unitary network and fractionate into different sub-networks. Here we identified two distinct subsystems within the DN – while both subsystems show common disinterest in externally-oriented visuospatial tasks, their functional profiles differ strikingly according to the preferred contents of thoughts, preferred modes of task requirement, and causative neural dynamics among network nodes. Specifically, one subsystem comprises key nodes of the frontotemporal semantic regions. This network shows moderate dislike to visuospatial tasks, shows proclivity for task-contexts with restraints on thoughts and responses, and prefers thoughts that are focused on other people. By contrast, the other subsystem comprises the cortical midline structure and angular gyri. This network shows strong aversion to visuospatial tasks, favours task-contexts allowing free self-generated thoughts without constraints, and prefers thoughts that are focused on self. Furthermore, causative connectivity reveals that task-contexts systematically alter the dynamics within and between subsystems, suggesting flexible adaption to situational demands. This ‘self/inward vs. others/outward’ separation within the broad DN resembles recent discoveries regarding a dyadic structure within the frontoparietal network that comprises regions controlling memories/thoughts vs. regions controlling sensory-motoric processes, and echoes burgeoning views that the brain is organised with a spectrum-like architecture along gradational changes of ‘inward vs. outward’ preferences. Significance Rather than construing the default network (DN) as ‘task-negative’ regions that passively react to off-task mind-wandering, researchers have begun to acknowledge the active role of the DN in supporting internally-directed cognition. Here we found a striking dichotomy within the DN in terms of the subsystems’ task-driven functional and connectivity profiles, extending beyond previous inferences using meta-analysis and resting-state fMRI. This dichotomy reflects a local manifestation of a macro-scale gradient representation spanning across the broad cerebral cortex. This cortical gradient increases its representational complexity, from primitive sensory and motoric processing, through lexical-semantic codes for language tasks, to abstract self-generated thoughts in task-free contexts. These findings enable a framework where the separate yet related literatures of semantic cognition and default-mode processes converge.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"123 1","pages":"5484 - 5501"},"PeriodicalIF":0.0,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83345805","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}
S. Bhumika, Mari Nakamura, Patrícia Valério, Magdalena Sołyga, Henrik Lindén, T. R. Barkat
Abstract Neuronal circuits are shaped by experience during time windows of increased plasticity in postnatal development. In the auditory system, the critical period for the simplest sounds—pure frequency tones—is well defined. Critical periods for more complex sounds remain to be elucidated. We used in vivo electrophysiological recordings in the mouse auditory cortex to demonstrate that passive exposure to frequency modulated sweeps (FMS) from postnatal day 31 to 38 leads to long-term changes in the temporal representation of sweep directions. Immunohistochemical analysis revealed a decreased percentage of layer 4 parvalbumin-positive (PV+) cells during this critical period, paralleled with a transient increase in responses to FMS, but not to pure tones. Preventing the PV+ cell decrease with continuous white noise exposure delayed the critical period onset, suggesting a reduction in inhibition as a mechanism for this plasticity. Our findings shed new light on the dependence of plastic windows on stimulus complexity that persistently sculpt the functional organization of the auditory cortex.
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