S. H. Lindström, S. Sundberg, M. Larsson, F. K. Andersson, J. Broman, Björn Granseth
Abstract The most common excitatory neurotransmitter in the central nervous system, glutamate, is loaded into synaptic vesicles by vesicular glutamate transporters (VGluTs). The primary isoforms, VGluT1 and 2, are expressed in complementary patterns throughout the brain and correlate with short-term synaptic plasticity. VGluT1 deficiency is observed in certain neurological disorders, and hemizygous (VGluT1+/−) mice display increased anxiety and depression, altered sensorimotor gating, and impairments in learning and memory. The synaptic mechanisms underlying these behavioral deficits are unknown. Here, we show that VGluT1+/− mice had decreased visual processing speeds during a sustained visual-spatial attention task. Furthermore, in vitro recordings of corticothalamic (CT) synapses revealed dramatic reductions in short-term facilitation, increased initial release probability, and earlier synaptic depression in VGluT1+/− mice. Our electron microscopy results show that VGluT1 concentration is reduced at CT synapses of hemizygous mice, but other features (such as vesicle number and active zone size) are unchanged. We conclude that VGluT1-haploinsuficiency decreases the dynamic range of gain modulation provided by CT feedback to the thalamus, and this deficiency contributes to the observed attentional processing deficit. We further hypothesize that VGluT1 concentration regulates release probability by applying a “brake” to an unidentified presynaptic protein that typically acts as a positive regulator of release.
{"title":"VGluT1 Deficiency Impairs Visual Attention and Reduces the Dynamic Range of Short-Term Plasticity at Corticothalamic Synapses","authors":"S. H. Lindström, S. Sundberg, M. Larsson, F. K. Andersson, J. Broman, Björn Granseth","doi":"10.1093/cercor/bhz204","DOIUrl":"https://doi.org/10.1093/cercor/bhz204","url":null,"abstract":"Abstract The most common excitatory neurotransmitter in the central nervous system, glutamate, is loaded into synaptic vesicles by vesicular glutamate transporters (VGluTs). The primary isoforms, VGluT1 and 2, are expressed in complementary patterns throughout the brain and correlate with short-term synaptic plasticity. VGluT1 deficiency is observed in certain neurological disorders, and hemizygous (VGluT1+/−) mice display increased anxiety and depression, altered sensorimotor gating, and impairments in learning and memory. The synaptic mechanisms underlying these behavioral deficits are unknown. Here, we show that VGluT1+/− mice had decreased visual processing speeds during a sustained visual-spatial attention task. Furthermore, in vitro recordings of corticothalamic (CT) synapses revealed dramatic reductions in short-term facilitation, increased initial release probability, and earlier synaptic depression in VGluT1+/− mice. Our electron microscopy results show that VGluT1 concentration is reduced at CT synapses of hemizygous mice, but other features (such as vesicle number and active zone size) are unchanged. We conclude that VGluT1-haploinsuficiency decreases the dynamic range of gain modulation provided by CT feedback to the thalamus, and this deficiency contributes to the observed attentional processing deficit. We further hypothesize that VGluT1 concentration regulates release probability by applying a “brake” to an unidentified presynaptic protein that typically acts as a positive regulator of release.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"12 1","pages":"1813 - 1829"},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84257624","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}
M. Brinkhuis, Á. Kristjánsson, B. Harvey, J. Brascamp
Abstract Priming of attention shifts involves the reduction in search RTs that occurs when target location or target features repeat. We used functional magnetic resonance imaging to investigate the neural basis of such attentional priming, specifically focusing on its temporal characteristics over trial sequences. We first replicated earlier findings by showing that repetition of target color and of target location from the immediately preceding trial both result in reduced blood oxygen level-dependent (BOLD) signals in a cortical network that encompasses occipital, parietal, and frontal cortices: lag-1 repetition suppression. While such lag-1 suppression can have a number of explanations, behaviorally, the influence of attentional priming extends further, with the influence of past search trials gradually decaying across multiple subsequent trials. Our results reveal that the same regions within the frontoparietal network that show lag-1 suppression, also show longer term BOLD reductions that diminish over the course of several trial presentations, keeping pace with the decaying behavioral influence of past target properties across trials. This distinct parallel between the across-trial patterns of cortical BOLD and search RT reductions, provides strong evidence that these cortical areas play a key role in attentional priming.
{"title":"Temporal Characteristics of Priming of Attention Shifts Are Mirrored by BOLD Response Patterns in the Frontoparietal Attention Network","authors":"M. Brinkhuis, Á. Kristjánsson, B. Harvey, J. Brascamp","doi":"10.1093/cercor/bhz238","DOIUrl":"https://doi.org/10.1093/cercor/bhz238","url":null,"abstract":"Abstract Priming of attention shifts involves the reduction in search RTs that occurs when target location or target features repeat. We used functional magnetic resonance imaging to investigate the neural basis of such attentional priming, specifically focusing on its temporal characteristics over trial sequences. We first replicated earlier findings by showing that repetition of target color and of target location from the immediately preceding trial both result in reduced blood oxygen level-dependent (BOLD) signals in a cortical network that encompasses occipital, parietal, and frontal cortices: lag-1 repetition suppression. While such lag-1 suppression can have a number of explanations, behaviorally, the influence of attentional priming extends further, with the influence of past search trials gradually decaying across multiple subsequent trials. Our results reveal that the same regions within the frontoparietal network that show lag-1 suppression, also show longer term BOLD reductions that diminish over the course of several trial presentations, keeping pace with the decaying behavioral influence of past target properties across trials. This distinct parallel between the across-trial patterns of cortical BOLD and search RT reductions, provides strong evidence that these cortical areas play a key role in attentional priming.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"43 1","pages":"2267 - 2280"},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77409591","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}
J. Pahle, M. Muhia, R. Wagener, Anja Tippmann, H. Bock, J. Graw, J. Herz, J. Staiger, A. Drakew, M. Kneussel, G. Rune, M. Frotscher, B. Brunne
Abstract Reelin is an extracellular matrix protein, known for its dual role in neuronal migration during brain development and in synaptic plasticity at adult stages. During the perinatal phase, Reelin expression switches from Cajal-Retzius (CR) cells, its main source before birth, to inhibitory interneurons (IN), the main source of Reelin in the adult forebrain. IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear. In this study, we used conditional knockout mice, which lack Reelin expression specifically in inhibitory INs, leading to a substantial reduction in total Reelin expression in the neocortex and dentate gyrus. Our results show that IN-specific Reelin knockout mice exhibit normal neuronal layering and normal behavior, including spatial reference memory. Although INs are the major source of Reelin within the adult stem cell niche, Reelin from INs does not contribute substantially to normal adult neurogenesis. While a closer look at the dentate gyrus revealed some unexpected alterations at the cellular level, including an increase in the number of Reelin expressing CR cells, overall our data suggest that Reelin derived from INs is less critical for cortex development and function than Reelin expressed by CR cells.
{"title":"Selective Inactivation of Reelin in Inhibitory Interneurons Leads to Subtle Changes in the Dentate Gyrus But Leaves Cortical Layering and Behavior Unaffected","authors":"J. Pahle, M. Muhia, R. Wagener, Anja Tippmann, H. Bock, J. Graw, J. Herz, J. Staiger, A. Drakew, M. Kneussel, G. Rune, M. Frotscher, B. Brunne","doi":"10.1093/cercor/bhz196","DOIUrl":"https://doi.org/10.1093/cercor/bhz196","url":null,"abstract":"Abstract Reelin is an extracellular matrix protein, known for its dual role in neuronal migration during brain development and in synaptic plasticity at adult stages. During the perinatal phase, Reelin expression switches from Cajal-Retzius (CR) cells, its main source before birth, to inhibitory interneurons (IN), the main source of Reelin in the adult forebrain. IN-derived Reelin has been associated with schizophrenia and temporal lobe epilepsy; however, the functional role of Reelin from INs is presently unclear. In this study, we used conditional knockout mice, which lack Reelin expression specifically in inhibitory INs, leading to a substantial reduction in total Reelin expression in the neocortex and dentate gyrus. Our results show that IN-specific Reelin knockout mice exhibit normal neuronal layering and normal behavior, including spatial reference memory. Although INs are the major source of Reelin within the adult stem cell niche, Reelin from INs does not contribute substantially to normal adult neurogenesis. While a closer look at the dentate gyrus revealed some unexpected alterations at the cellular level, including an increase in the number of Reelin expressing CR cells, overall our data suggest that Reelin derived from INs is less critical for cortex development and function than Reelin expressed by CR cells.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"9 1","pages":"1688 - 1707"},"PeriodicalIF":0.0,"publicationDate":"2019-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77687596","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}
M. Turégano-Lopez, A. Santuy, J. DeFelipe, Á. Merchán-Pérez
Abstract Multivesicular bodies (MVBs) are membrane-bound organelles that belong to the endosomal pathway. They participate in the transport, sorting, storage, recycling, degradation, and release of multiple substances. They interchange cargo with other organelles and participate in their renovation and degradation. We have used focused ion beam milling and scanning electron microscopy (FIB-SEM) to obtain stacks of serial sections from the neuropil of the somatosensory cortex of the juvenile rat. Using dedicated software, we have 3D-reconstructed 1618 MVBs. The mean density of MVBs was 0.21 per cubic micron. They were unequally distributed between dendrites (39.14%), axons (18.16%), and nonsynaptic cell processes (42.70%). About one out of five MVBs (18.16%) were docked on mitochondria, representing the process by which the endosomal pathway participates in mitochondrial maintenance. Other features of MVBs, such as the presence of tubular protrusions (6.66%) or clathrin coats (19.74%) can also be interpreted in functional terms, since both are typical of early endosomes. The sizes of MVBs follow a lognormal distribution, with differences across cortical layers and cellular compartments. The mean volume of dendritic MVBs is more than twice as large as the volume of axonic MVBs. In layer I, they are smaller, on average, than in the other layers.
{"title":"Size, Shape, and Distribution of Multivesicular Bodies in the Juvenile Rat Somatosensory Cortex: A 3D Electron Microscopy Study","authors":"M. Turégano-Lopez, A. Santuy, J. DeFelipe, Á. Merchán-Pérez","doi":"10.1093/cercor/bhz211","DOIUrl":"https://doi.org/10.1093/cercor/bhz211","url":null,"abstract":"Abstract Multivesicular bodies (MVBs) are membrane-bound organelles that belong to the endosomal pathway. They participate in the transport, sorting, storage, recycling, degradation, and release of multiple substances. They interchange cargo with other organelles and participate in their renovation and degradation. We have used focused ion beam milling and scanning electron microscopy (FIB-SEM) to obtain stacks of serial sections from the neuropil of the somatosensory cortex of the juvenile rat. Using dedicated software, we have 3D-reconstructed 1618 MVBs. The mean density of MVBs was 0.21 per cubic micron. They were unequally distributed between dendrites (39.14%), axons (18.16%), and nonsynaptic cell processes (42.70%). About one out of five MVBs (18.16%) were docked on mitochondria, representing the process by which the endosomal pathway participates in mitochondrial maintenance. Other features of MVBs, such as the presence of tubular protrusions (6.66%) or clathrin coats (19.74%) can also be interpreted in functional terms, since both are typical of early endosomes. The sizes of MVBs follow a lognormal distribution, with differences across cortical layers and cellular compartments. The mean volume of dendritic MVBs is more than twice as large as the volume of axonic MVBs. In layer I, they are smaller, on average, than in the other layers.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"3 1","pages":"1887 - 1901"},"PeriodicalIF":0.0,"publicationDate":"2019-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87416418","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}
Abstract The development of executive function is linked to maturation of prefrontal cortex (PFC) in childhood. Childhood obesity has been associated with changes in brain structure, particularly in PFC, as well as deficits in executive functions. We aimed to determine whether differences in cortical structure mediate the relationship between executive function and childhood obesity. We analyzed MR-derived measures of cortical thickness for 2700 children between the ages of 9 and 11 years, recruited as part of the NIH Adolescent Brain and Cognitive Development (ABCD) study. We related our findings to measures of executive function and body mass index (BMI). In our analysis, increased BMI was associated with significantly reduced mean cortical thickness, as well as specific bilateral reduced cortical thickness in prefrontal cortical regions. This relationship remained after accounting for age, sex, race, parental education, household income, birth-weight, and in-scanner motion. Increased BMI was also associated with lower executive function. Reduced thickness in the rostral medial and superior frontal cortex, the inferior frontal gyrus, and the lateral orbitofrontal cortex partially accounted for reductions in executive function. These results suggest that childhood obesity is associated with compromised executive function. This relationship may be partly explained by BMI-associated reduced cortical thickness in the PFC.
{"title":"Childhood Obesity, Cortical Structure, and Executive Function in Healthy Children","authors":"L. Ronan, A. Alexander-Bloch, P. Fletcher","doi":"10.1093/cercor/bhz257","DOIUrl":"https://doi.org/10.1093/cercor/bhz257","url":null,"abstract":"Abstract The development of executive function is linked to maturation of prefrontal cortex (PFC) in childhood. Childhood obesity has been associated with changes in brain structure, particularly in PFC, as well as deficits in executive functions. We aimed to determine whether differences in cortical structure mediate the relationship between executive function and childhood obesity. We analyzed MR-derived measures of cortical thickness for 2700 children between the ages of 9 and 11 years, recruited as part of the NIH Adolescent Brain and Cognitive Development (ABCD) study. We related our findings to measures of executive function and body mass index (BMI). In our analysis, increased BMI was associated with significantly reduced mean cortical thickness, as well as specific bilateral reduced cortical thickness in prefrontal cortical regions. This relationship remained after accounting for age, sex, race, parental education, household income, birth-weight, and in-scanner motion. Increased BMI was also associated with lower executive function. Reduced thickness in the rostral medial and superior frontal cortex, the inferior frontal gyrus, and the lateral orbitofrontal cortex partially accounted for reductions in executive function. These results suggest that childhood obesity is associated with compromised executive function. This relationship may be partly explained by BMI-associated reduced cortical thickness in the PFC.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"46 1","pages":"2519 - 2528"},"PeriodicalIF":0.0,"publicationDate":"2019-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76247225","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}
Timo Saarinen, J. Kujala, H. Laaksonen, A. Jalava, R. Salmelin
Abstract Both motor and cognitive aspects of behavior depend on dynamic, accurately timed neural processes in large-scale brain networks. Here, we studied synchronous interplay between cortical regions during production of cognitive-motor sequences in humans. Specifically, variants of handwriting that differed in motor variability, linguistic content, and memorization of movement cues were contrasted to unveil functional sensitivity of corticocortical connections. Data-driven magnetoencephalography mapping (n = 10) uncovered modulation of mostly left-hemispheric corticocortical interactions, as quantified by relative changes in phase synchronization. At low frequencies (~2–13 Hz), enhanced frontoparietal synchrony was related to regular handwriting, whereas premotor cortical regions synchronized for simple loop production and temporo-occipital areas for a writing task substituting normal script with loop patterns. At the beta-to-gamma band (~13–45 Hz), enhanced synchrony was observed for regular handwriting in the central and frontoparietal regions, including connections between the sensorimotor and supplementary motor cortices and between the parietal and dorsal premotor/precentral cortices. Interpreted within a modular framework, these modulations of synchrony mainly highlighted interactions of the putative pericentral subsystem of hand coordination and the frontoparietal subsystem mediating working memory operations. As part of cortical dynamics, interregional phase synchrony varies depending on task demands in production of cognitive-motor sequences.
{"title":"Task-Modulated Corticocortical Synchrony in the Cognitive-Motor Network Supporting Handwriting","authors":"Timo Saarinen, J. Kujala, H. Laaksonen, A. Jalava, R. Salmelin","doi":"10.1093/cercor/bhz210","DOIUrl":"https://doi.org/10.1093/cercor/bhz210","url":null,"abstract":"Abstract Both motor and cognitive aspects of behavior depend on dynamic, accurately timed neural processes in large-scale brain networks. Here, we studied synchronous interplay between cortical regions during production of cognitive-motor sequences in humans. Specifically, variants of handwriting that differed in motor variability, linguistic content, and memorization of movement cues were contrasted to unveil functional sensitivity of corticocortical connections. Data-driven magnetoencephalography mapping (n = 10) uncovered modulation of mostly left-hemispheric corticocortical interactions, as quantified by relative changes in phase synchronization. At low frequencies (~2–13 Hz), enhanced frontoparietal synchrony was related to regular handwriting, whereas premotor cortical regions synchronized for simple loop production and temporo-occipital areas for a writing task substituting normal script with loop patterns. At the beta-to-gamma band (~13–45 Hz), enhanced synchrony was observed for regular handwriting in the central and frontoparietal regions, including connections between the sensorimotor and supplementary motor cortices and between the parietal and dorsal premotor/precentral cortices. Interpreted within a modular framework, these modulations of synchrony mainly highlighted interactions of the putative pericentral subsystem of hand coordination and the frontoparietal subsystem mediating working memory operations. As part of cortical dynamics, interregional phase synchrony varies depending on task demands in production of cognitive-motor sequences.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"93 1","pages":"1871 - 1886"},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87663240","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}
Abstract To control our actions efficiently, our brain represents our body based on a combination of visual and proprioceptive cues, weighted according to how (un)reliable—how precise—each respective modality is in a given context. However, perceptual experiments in other modalities suggest that the weights assigned to sensory cues are also modulated “top-down” by attention. Here, we asked whether during action, attention can likewise modulate the weights (i.e., precision) assigned to visual versus proprioceptive information about body position. Participants controlled a virtual hand (VH) via a data glove, matching either the VH or their (unseen) real hand (RH) movements to a target, and thus adopting a ``visual'' or ``proprioceptive'' attentional set, under varying levels of visuo-proprioceptive congruence and visibility. Functional magnetic resonance imaging (fMRI) revealed increased activation of the multisensory superior parietal lobe (SPL) during the VH task and increased activation of the secondary somatosensory cortex (S2) during the RH task. Dynamic causal modeling (DCM) showed that these activity changes were the result of selective, diametrical gain modulations in the primary visual cortex (V1) and the S2. These results suggest that endogenous attention can balance the gain of visual versus proprioceptive brain areas, thus contextualizing their influence on multisensory areas representing the body for action.
{"title":"Attentional Modulation of Vision Versus Proprioception During Action","authors":"Jakub Limanowski, Karl J. Friston","doi":"10.1093/cercor/bhz192","DOIUrl":"https://doi.org/10.1093/cercor/bhz192","url":null,"abstract":"Abstract To control our actions efficiently, our brain represents our body based on a combination of visual and proprioceptive cues, weighted according to how (un)reliable—how precise—each respective modality is in a given context. However, perceptual experiments in other modalities suggest that the weights assigned to sensory cues are also modulated “top-down” by attention. Here, we asked whether during action, attention can likewise modulate the weights (i.e., precision) assigned to visual versus proprioceptive information about body position. Participants controlled a virtual hand (VH) via a data glove, matching either the VH or their (unseen) real hand (RH) movements to a target, and thus adopting a ``visual'' or ``proprioceptive'' attentional set, under varying levels of visuo-proprioceptive congruence and visibility. Functional magnetic resonance imaging (fMRI) revealed increased activation of the multisensory superior parietal lobe (SPL) during the VH task and increased activation of the secondary somatosensory cortex (S2) during the RH task. Dynamic causal modeling (DCM) showed that these activity changes were the result of selective, diametrical gain modulations in the primary visual cortex (V1) and the S2. These results suggest that endogenous attention can balance the gain of visual versus proprioceptive brain areas, thus contextualizing their influence on multisensory areas representing the body for action.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"2015 1","pages":"1637 - 1648"},"PeriodicalIF":0.0,"publicationDate":"2019-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88916626","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}
C. Barz, P. Garderes, D. Ganea, Sven Reischauer, D. Feldmeyer, F. Haiss
Sparse population activity is a hallmark of supra-granular sensory neurons in neocortex. The mechanisms underlying sparseness are not well understood because a direct link between the neurons activated in vivo and their cellular properties investigated in vitro has been missing. We used two-photon calcium imaging to identify a subset of neurons in layer L2/3 (L2/3) of mouse primary somatosensory cortex that are highly active following principal whisker vibrotactile stimulation. These high responders were then tagged using photoconvertible green fluorescent protein for subsequent targeting in the brain slice using intracellular patch-clamp recordings and biocytin staining. This approach allowed us to investigate the structural and functional properties of high responders that distinguish them from less active control cells. Compared to less responsive L2/3 neurons, high responders displayed increased levels of stimulus-evoked and spontaneous activity, elevated noise and spontaneous pair-wise correlations, and stronger coupling to the population response. Intrinsic excitability was reduced in high responders, while other electrophysiological and morphological parameters were unchanged. Thus, the choice of which neurons participate in stimulus encoding may largely be determined by network connectivity rather than by cellular structure and function.
{"title":"Functional and Structural Properties of Highly Responsive Somatosensory Neurons in Mouse Barrel Cortex","authors":"C. Barz, P. Garderes, D. Ganea, Sven Reischauer, D. Feldmeyer, F. Haiss","doi":"10.1101/789347","DOIUrl":"https://doi.org/10.1101/789347","url":null,"abstract":"Sparse population activity is a hallmark of supra-granular sensory neurons in neocortex. The mechanisms underlying sparseness are not well understood because a direct link between the neurons activated in vivo and their cellular properties investigated in vitro has been missing. We used two-photon calcium imaging to identify a subset of neurons in layer L2/3 (L2/3) of mouse primary somatosensory cortex that are highly active following principal whisker vibrotactile stimulation. These high responders were then tagged using photoconvertible green fluorescent protein for subsequent targeting in the brain slice using intracellular patch-clamp recordings and biocytin staining. This approach allowed us to investigate the structural and functional properties of high responders that distinguish them from less active control cells. Compared to less responsive L2/3 neurons, high responders displayed increased levels of stimulus-evoked and spontaneous activity, elevated noise and spontaneous pair-wise correlations, and stronger coupling to the population response. Intrinsic excitability was reduced in high responders, while other electrophysiological and morphological parameters were unchanged. Thus, the choice of which neurons participate in stimulus encoding may largely be determined by network connectivity rather than by cellular structure and function.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"67 1","pages":"4533 - 4553"},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83947513","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}
L. Fornia, M. Rossi, M. Rabuffetti, A. Leonetti, G. Puglisi, L. Viganó, L. Simone, H. Howells, A. Bellacicca, L. Bello, G. Cerri
Abstract Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.
{"title":"Direct Electrical Stimulation of Premotor Areas: Different Effects on Hand Muscle Activity during Object Manipulation","authors":"L. Fornia, M. Rossi, M. Rabuffetti, A. Leonetti, G. Puglisi, L. Viganó, L. Simone, H. Howells, A. Bellacicca, L. Bello, G. Cerri","doi":"10.1093/cercor/bhz139","DOIUrl":"https://doi.org/10.1093/cercor/bhz139","url":null,"abstract":"Abstract Dorsal and ventral premotor (dPM and vPM) areas are crucial in control of hand muscles during object manipulation, although their respective role in humans is still debated. In patients undergoing awake surgery for brain tumors, we studied the effect of direct electrical stimulation (DES) of the premotor cortex on the execution of a hand manipulation task (HMt). A quantitative analysis of the activity of extrinsic and intrinsic hand muscles recorded during and in absence of DES was performed. Results showed that DES applied to premotor areas significantly impaired HMt execution, affecting task-related muscle activity with specific features related to the stimulated area. Stimulation of dorsal vPM induced both a complete task arrest and clumsy task execution, characterized by general muscle suppression. Stimulation of ventrocaudal dPM evoked a complete task arrest mainly due to a dysfunctional recruitment of hand muscles engaged in task execution. These results suggest that vPM and dPM contribute differently to the control of hand muscles during object manipulation. Stimulation of both areas showed a significant impact on motor output, although the different effects suggest a stronger relationship of dPM with the corticomotoneuronal circuit promoting muscle recruitment and a role for vPM in supporting sensorimotor integration.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"10 1","pages":"391 - 405"},"PeriodicalIF":0.0,"publicationDate":"2019-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81913124","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}
K. Nordengen, K. Nordengen, C. Morland, Barbara S. Slusher, Gundersen, Gundersen
Abstract While a lot is known about classical, anterograde neurotransmission, less is known about the mechanisms and molecules involved in retrograde neurotransmission. Our hypothesis is that N-acetylaspartylglutamate (NAAG), the most abundant dipeptide in the brain, may act as a retrograde transmitter in the brain. NAAG was predominantly localized in dendritic compartments of glutamatergic synapses in the intact hippocampus, where it was present in close proximity to synaptic-like vesicles. In acute hippocampal slices, NAAG was depleted from postsynaptic dendritic elements during neuronal stimulation induced by depolarizing concentrations of potassium or by exposure to glutamate receptor (GluR) agonists. The depletion was completely blocked by botulinum toxin B and strictly dependent on extracellular calcium, indicating exocytotic release. In contrast, there were low levels of NAAG and no effect by depolarization or GluR agonists in presynaptic glutamatergic terminals or GABAergic pre- and postsynaptic elements. Together these data suggest a possible role for NAAG as a retrograde signaling molecule at glutamatergic synapses via exocytotic release.
{"title":"Dendritic Localization and Exocytosis of NAAG in the Rat Hippocampus","authors":"K. Nordengen, K. Nordengen, C. Morland, Barbara S. Slusher, Gundersen, Gundersen","doi":"10.1093/cercor/bhz176","DOIUrl":"https://doi.org/10.1093/cercor/bhz176","url":null,"abstract":"Abstract While a lot is known about classical, anterograde neurotransmission, less is known about the mechanisms and molecules involved in retrograde neurotransmission. Our hypothesis is that N-acetylaspartylglutamate (NAAG), the most abundant dipeptide in the brain, may act as a retrograde transmitter in the brain. NAAG was predominantly localized in dendritic compartments of glutamatergic synapses in the intact hippocampus, where it was present in close proximity to synaptic-like vesicles. In acute hippocampal slices, NAAG was depleted from postsynaptic dendritic elements during neuronal stimulation induced by depolarizing concentrations of potassium or by exposure to glutamate receptor (GluR) agonists. The depletion was completely blocked by botulinum toxin B and strictly dependent on extracellular calcium, indicating exocytotic release. In contrast, there were low levels of NAAG and no effect by depolarization or GluR agonists in presynaptic glutamatergic terminals or GABAergic pre- and postsynaptic elements. Together these data suggest a possible role for NAAG as a retrograde signaling molecule at glutamatergic synapses via exocytotic release.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"111 1","pages":"1422 - 1435"},"PeriodicalIF":0.0,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82468550","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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