Neuroscience
The pathways of interoceptive awareness.
Publication Date: 2009 Nov 1 PMID: 19881506
Authors: Khalsa, S. S. - Rudrauf, D. - Feinstein, J. S. - Tranel, D.
Journal: Nat Neurosci
A network of cortical brain regions, including the insula and anterior cingulate cortex (ACC), has been proposed as the critical and sole substrate for interoceptive awareness. Combining lesion and pharmacological approaches in humans, we found that the insula and ACC were not critical for awareness of heartbeat sensations. Instead, this awareness was mediated by both somatosensory afferents from the skin and a network that included the insula and ACC. Together, these pathways enable the core human experience of the cardiovascular state of the body.
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Authors: Khalsa, S. S. - Rudrauf, D. - Feinstein, J. S. - Tranel, D.
Journal: Nat Neurosci
A network of cortical brain regions, including the insula and anterior cingulate cortex (ACC), has been proposed as the critical and sole substrate for interoceptive awareness. Combining lesion and pharmacological approaches in humans, we found that the insula and ACC were not critical for awareness of heartbeat sensations. Instead, this awareness was mediated by both somatosensory afferents from the skin and a network that included the insula and ACC. Together, these pathways enable the core human experience of the cardiovascular state of the body.
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A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning.
Publication Date: 2009 Nov 1 PMID: 19881505
Authors: Kirilly, D. - Gu, Y. - Huang, Y. - Wu, Z. - Bashirullah, A. - Low, B. C. - Kolodkin, A. L. - Wang, H. - Yu, F.
Journal: Nat Neurosci
Pruning that selectively eliminates neuronal processes is crucial for the refinement of neural circuits during development. In Drosophila, the class IV dendritic arborization neuron (ddaC) undergoes pruning to remove its larval dendrites during metamorphosis. We identified Sox14 as a transcription factor that was necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We found that Sox14 mediated dendrite pruning by directly regulating the expression of the target gene mical. mical encodes a large cytosolic protein with multiple domains that are known to associate with cytoskeletal components. mical mutants had marked severing defects during dendrite pruning that were similar to those of sox14 mutants. Overexpression of Mical could significantly rescue pruning defects in sox14 mutants, suggesting that Mical is a major downstream target of Sox14 during pruning. Thus, our findings indicate that a previously unknown pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing.
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Authors: Kirilly, D. - Gu, Y. - Huang, Y. - Wu, Z. - Bashirullah, A. - Low, B. C. - Kolodkin, A. L. - Wang, H. - Yu, F.
Journal: Nat Neurosci
Pruning that selectively eliminates neuronal processes is crucial for the refinement of neural circuits during development. In Drosophila, the class IV dendritic arborization neuron (ddaC) undergoes pruning to remove its larval dendrites during metamorphosis. We identified Sox14 as a transcription factor that was necessary and sufficient to mediate dendrite severing during pruning in response to ecdysone signaling. We found that Sox14 mediated dendrite pruning by directly regulating the expression of the target gene mical. mical encodes a large cytosolic protein with multiple domains that are known to associate with cytoskeletal components. mical mutants had marked severing defects during dendrite pruning that were similar to those of sox14 mutants. Overexpression of Mical could significantly rescue pruning defects in sox14 mutants, suggesting that Mical is a major downstream target of Sox14 during pruning. Thus, our findings indicate that a previously unknown pathway composed of Sox14 and its cytoskeletal target Mical governs dendrite severing.
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Adult generation of glutamatergic olfactory bulb interneurons.
Publication Date: 2009 Nov 1 PMID: 19881504
Authors: Brill, M. S. - Ninkovic, J. - Winpenny, E. - Hodge, R. D. - Ozen, I. - Yang, R. - Lepier, A. - Gascon, S. - Erdelyi, F. - Szabo, G. - Parras, C. - Guillemot, F. - Frotscher, M. - Berninger, B. - Hevner, R. F. - Raineteau, O. - Gotz, M.
Journal: Nat Neurosci
The adult mouse subependymal zone (SEZ) harbors neural stem cells that are thought to exclusively generate GABAergic interneurons of the olfactory bulb. We examined the adult generation of glutamatergic juxtaglomerular neurons, which had dendritic arborizations that projected into adjacent glomeruli, identifying them as short-axon cells. Fate mapping revealed that these originate from Neurog2- and Tbr2-expressing progenitors located in the dorsal region of the SEZ. Examination of the progenitors of these glutamatergic interneurons allowed us to determine the sequential expression of transcription factors in these cells that are thought to be hallmarks of glutamatergic neurogenesis in the developing cerebral cortex and adult hippocampus. Indeed, the molecular specification of these SEZ progenitors allowed for their recruitment into the cerebral cortex after a lesion was induced. Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair.
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Authors: Brill, M. S. - Ninkovic, J. - Winpenny, E. - Hodge, R. D. - Ozen, I. - Yang, R. - Lepier, A. - Gascon, S. - Erdelyi, F. - Szabo, G. - Parras, C. - Guillemot, F. - Frotscher, M. - Berninger, B. - Hevner, R. F. - Raineteau, O. - Gotz, M.
Journal: Nat Neurosci
The adult mouse subependymal zone (SEZ) harbors neural stem cells that are thought to exclusively generate GABAergic interneurons of the olfactory bulb. We examined the adult generation of glutamatergic juxtaglomerular neurons, which had dendritic arborizations that projected into adjacent glomeruli, identifying them as short-axon cells. Fate mapping revealed that these originate from Neurog2- and Tbr2-expressing progenitors located in the dorsal region of the SEZ. Examination of the progenitors of these glutamatergic interneurons allowed us to determine the sequential expression of transcription factors in these cells that are thought to be hallmarks of glutamatergic neurogenesis in the developing cerebral cortex and adult hippocampus. Indeed, the molecular specification of these SEZ progenitors allowed for their recruitment into the cerebral cortex after a lesion was induced. Taken together, our data indicate that SEZ progenitors not only produce a population of adult-born glutamatergic juxtaglomerular neurons, but may also provide a previously unknown source of progenitors for endogenous repair.
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Self-generated theta oscillations in the hippocampus.
Publication Date: 2009 Nov 1 PMID: 19881503
Authors: Goutagny, R. - Jackson, J. - Williams, S.
Journal: Nat Neurosci
Hippocampal theta rhythm is crucial for spatial memory and is thought to be generated by extrinsic inputs. In contrast, using a complete rat hippocampus in vitro, we found several intrinsic, atropine-resistant theta generators in CA1. These oscillators were organized along the septotemporal axis and arose independently from CA3. Our results suggest that CA1 theta rhythm can emerge from the coupling of multiple autonomous hippocampal theta oscillators.
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Authors: Goutagny, R. - Jackson, J. - Williams, S.
Journal: Nat Neurosci
Hippocampal theta rhythm is crucial for spatial memory and is thought to be generated by extrinsic inputs. In contrast, using a complete rat hippocampus in vitro, we found several intrinsic, atropine-resistant theta generators in CA1. These oscillators were organized along the septotemporal axis and arose independently from CA3. Our results suggest that CA1 theta rhythm can emerge from the coupling of multiple autonomous hippocampal theta oscillators.
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Input normalization by global feedforward inhibition expands cortical dynamic range.
Publication Date: 2009 Nov 1 PMID: 19881502
Authors: Pouille, F. - Marin-Burgin, A. - Adesnik, H. - Atallah, B. V. - Scanziani, M.
Journal: Nat Neurosci
The cortex is sensitive to weak stimuli, but responds to stronger inputs without saturating. The mechanisms that enable this wide range of operation are not fully understood. We found that the amplitude of excitatory synaptic currents necessary to fire rodent pyramidal cells, the threshold excitatory current, increased with stimulus strength. Consequently, the relative contribution of individual afferents in firing a neuron was inversely proportional to the total number of active afferents. Feedforward inhibition, acting homogeneously across pyramidal cells, ensured that threshold excitatory currents increased with stimulus strength. In contrast, heterogeneities in the distribution of excitatory currents in the neuronal population determined the specific set of pyramidal cells recruited. Together, these mechanisms expand the range of afferent input strengths that neuronal populations can represent.
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Authors: Pouille, F. - Marin-Burgin, A. - Adesnik, H. - Atallah, B. V. - Scanziani, M.
Journal: Nat Neurosci
The cortex is sensitive to weak stimuli, but responds to stronger inputs without saturating. The mechanisms that enable this wide range of operation are not fully understood. We found that the amplitude of excitatory synaptic currents necessary to fire rodent pyramidal cells, the threshold excitatory current, increased with stimulus strength. Consequently, the relative contribution of individual afferents in firing a neuron was inversely proportional to the total number of active afferents. Feedforward inhibition, acting homogeneously across pyramidal cells, ensured that threshold excitatory currents increased with stimulus strength. In contrast, heterogeneities in the distribution of excitatory currents in the neuronal population determined the specific set of pyramidal cells recruited. Together, these mechanisms expand the range of afferent input strengths that neuronal populations can represent.
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Optimizing brain processing.
Publication Date: 2009 Nov PMID: 19861947
Authors: Thiele, A.
Journal: Nat Neurosci
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Authors: Thiele, A.
Journal: Nat Neurosci
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How to button a bouton with alpha(2)deltas.
Publication Date: 2009 Nov PMID: 19861946
Authors: Sigrist, S. J. - Plested, A. J.
Journal: Nat Neurosci
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Authors: Sigrist, S. J. - Plested, A. J.
Journal: Nat Neurosci
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Any kind of mother in a storm.
Publication Date: 2009 Nov PMID: 19861945
Authors: Sapolsky, R.
Journal: Nat Neurosci
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Authors: Sapolsky, R.
Journal: Nat Neurosci
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Learning to see in stereo.
Publication Date: 2009 Nov PMID: 19861944
Authors: Mitchell, D. - Levi, D. - Bavelier, D.
Journal: Nat Neurosci
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Authors: Mitchell, D. - Levi, D. - Bavelier, D.
Journal: Nat Neurosci
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Sleep deprivation differentially impairs cognitive performance in abstinent methylenedioxymethamphetamine ("ecstasy") users.
Publication Date: 2009 Nov 4 PMID: 19890014
Authors: McCann, U. D. - Wilson, M. J. - Sgambati, F. P. - Ricaurte, G. A.
Journal: J Neurosci
Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5 d inpatient study in a clinical research unit. Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule. At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory. Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with sleep deprivation.
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Authors: McCann, U. D. - Wilson, M. J. - Sgambati, F. P. - Ricaurte, G. A.
Journal: J Neurosci
Methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular recreational drug and brain serotonin (5-HT) neurotoxin. Neuroimaging data indicate that some human MDMA users develop persistent deficits in brain 5-HT neuronal markers. Although the consequences of MDMA-induced 5-HT neurotoxicity are not fully understood, abstinent MDMA users have been found to have subtle cognitive deficits and altered sleep architecture. The present study sought to test the hypothesis that sleep disturbance plays a role in cognitive deficits in MDMA users. Nineteen abstinent MDMA users and 21 control subjects participated in a 5 d inpatient study in a clinical research unit. Baseline sleep quality was measured using the Pittsburgh Sleep Quality Inventory. Cognitive performance was tested three times daily using a computerized cognitive battery. On the third day of admission, subjects began a 40 h sleep deprivation period and continued cognitive testing using the same daily schedule. At baseline, MDMA users performed less accurately than controls on a task of working memory and more impulsively on four of the seven computerized tests. During sleep deprivation, MDMA users, but not controls, became increasingly impulsive, performing more rapidly at the expense of accuracy on tasks of working and short-term memory. Tests of mediation implicated baseline sleep disturbance in the cognitive decline seen during sleep deprivation. These findings are the first to demonstrate that memory problems in MDMA users may be related, at least in part, to sleep disturbance and suggest that cognitive deficits in MDMA users may become more prominent in situations associated with sleep deprivation.
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Inositol 1,4,5-trisphosphate 3-kinase a functions as a scaffold for synaptic Rac signaling.
Publication Date: 2009 Nov 4 PMID: 19890013
Authors: Kim, I. H. - Park, S. K. - Hong, S. T. - Jo, Y. S. - Kim, E. J. - Park, E. H. - Han, S. B. - Shin, H. S. - Sun, W. - Kim, H. T. - Soderling, S. H. - Kim, H.
Journal: J Neurosci
Activity-dependent alterations of synaptic contacts are crucial for synaptic plasticity. The formation of new dendritic spines and synapses is known to require actin cytoskeletal reorganization specifically during neural activation phases. Yet the site-specific and time-dependent mechanisms modulating actin dynamics in mature neurons are not well understood. In this study, we show that actin dynamics in spines is regulated by a Rac anchoring and targeting function of inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A), independent of its kinase activity. On neural activation, IP(3)K-A bound directly to activated Rac1 and recruited it to the actin cytoskeleton in the postsynaptic area. This focal targeting of activated Rac1 induced spine formation through actin dynamics downstream of Rac signaling. Consistent with the scaffolding role of IP(3)K-A, IP(3)K-A knock-out mice exhibited defects in accumulation of PAK1 by long-term potentiation-inducing stimulation. This deficiency resulted in a reduction in the reorganization of actin cytoskeletal structures in the synaptic area of dentate gyrus. Moreover, IP(3)K-A knock-out mice showed deficits of synaptic plasticity in perforant path and in hippocampal-dependent memory performances. These data support a novel model in which IP(3)K-A is critical for the spatial and temporal regulation of spine actin remodeling, synaptic plasticity, and learning and memory via an activity-dependent Rac scaffolding mechanism.
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Authors: Kim, I. H. - Park, S. K. - Hong, S. T. - Jo, Y. S. - Kim, E. J. - Park, E. H. - Han, S. B. - Shin, H. S. - Sun, W. - Kim, H. T. - Soderling, S. H. - Kim, H.
Journal: J Neurosci
Activity-dependent alterations of synaptic contacts are crucial for synaptic plasticity. The formation of new dendritic spines and synapses is known to require actin cytoskeletal reorganization specifically during neural activation phases. Yet the site-specific and time-dependent mechanisms modulating actin dynamics in mature neurons are not well understood. In this study, we show that actin dynamics in spines is regulated by a Rac anchoring and targeting function of inositol 1,4,5-trisphosphate 3-kinase A (IP(3)K-A), independent of its kinase activity. On neural activation, IP(3)K-A bound directly to activated Rac1 and recruited it to the actin cytoskeleton in the postsynaptic area. This focal targeting of activated Rac1 induced spine formation through actin dynamics downstream of Rac signaling. Consistent with the scaffolding role of IP(3)K-A, IP(3)K-A knock-out mice exhibited defects in accumulation of PAK1 by long-term potentiation-inducing stimulation. This deficiency resulted in a reduction in the reorganization of actin cytoskeletal structures in the synaptic area of dentate gyrus. Moreover, IP(3)K-A knock-out mice showed deficits of synaptic plasticity in perforant path and in hippocampal-dependent memory performances. These data support a novel model in which IP(3)K-A is critical for the spatial and temporal regulation of spine actin remodeling, synaptic plasticity, and learning and memory via an activity-dependent Rac scaffolding mechanism.
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Visual learning shapes the processing of complex movement stimuli in the human brain.
Publication Date: 2009 Nov 4 PMID: 19890012
Authors: Jastorff, J. - Kourtzi, Z. - Giese, M. A.
Journal: J Neurosci
Recognition of actions and complex movements is fundamental for social interactions and action understanding. While the relationship between motor expertise and visual recognition of body movements has received a vast amount of interest, the role of visual learning remains largely unexplored. Combining psychophysics and functional magnetic resonance imaging (fMRI) experiments, we investigated neural correlates of visual learning of complex movements. Subjects were trained to visually discriminate between very similar complex movement stimuli generated by motion morphing that were either compatible (experiments 1 and 2) or incompatible (experiment 3) with human movement execution. Employing an fMRI adaptation paradigm as index of discriminability, we scanned human subjects before and after discrimination training. The results of experiment 1 revealed three different effects as a consequence of training: (1) Emerging fMRI-selective adaptation in general motion-related areas (hMT/V5+, KO/V3b) for the differences between human-like movements. (2) Enhanced of fMRI-selective adaptation already present before training in biological motion-related areas (pSTS, FBA). (3) Changes covarying with task difficulty in frontal areas. Moreover, the observed activity changes were specific to the trained movement patterns (experiment 2). The results of experiment 3, testing artificial movement stimuli, were strikingly similar to the results obtained for human movements. General and biological motion-related areas showed movement-specific changes in fMRI-selective adaptation for the differences between the stimuli after training. These results support the existence of a powerful visual machinery for the learning of complex motion patterns that is independent of motor execution. We thus propose a key role of visual learning in action recognition.
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Authors: Jastorff, J. - Kourtzi, Z. - Giese, M. A.
Journal: J Neurosci
Recognition of actions and complex movements is fundamental for social interactions and action understanding. While the relationship between motor expertise and visual recognition of body movements has received a vast amount of interest, the role of visual learning remains largely unexplored. Combining psychophysics and functional magnetic resonance imaging (fMRI) experiments, we investigated neural correlates of visual learning of complex movements. Subjects were trained to visually discriminate between very similar complex movement stimuli generated by motion morphing that were either compatible (experiments 1 and 2) or incompatible (experiment 3) with human movement execution. Employing an fMRI adaptation paradigm as index of discriminability, we scanned human subjects before and after discrimination training. The results of experiment 1 revealed three different effects as a consequence of training: (1) Emerging fMRI-selective adaptation in general motion-related areas (hMT/V5+, KO/V3b) for the differences between human-like movements. (2) Enhanced of fMRI-selective adaptation already present before training in biological motion-related areas (pSTS, FBA). (3) Changes covarying with task difficulty in frontal areas. Moreover, the observed activity changes were specific to the trained movement patterns (experiment 2). The results of experiment 3, testing artificial movement stimuli, were strikingly similar to the results obtained for human movements. General and biological motion-related areas showed movement-specific changes in fMRI-selective adaptation for the differences between the stimuli after training. These results support the existence of a powerful visual machinery for the learning of complex motion patterns that is independent of motor execution. We thus propose a key role of visual learning in action recognition.
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Enduring reversal of neuropathic pain by a single intrathecal injection of adenosine 2A receptor agonists: a novel therapy for neuropathic pain.
Publication Date: 2009 Nov 4 PMID: 19890011
Authors: Loram, L. C. - Harrison, J. A. - Sloane, E. M. - Hutchinson, M. R. - Sholar, P. - Taylor, F. R. - Berkelhammer, D. - Coats, B. D. - Poole, S. - Milligan, E. D. - Maier, S. F. - Rieger, J. - Watkins, L. R.
Journal: J Neurosci
Previous studies of peripheral immune cells have documented that activation of adenosine 2A receptors (A(2A)Rs) decrease proinflammatory cytokine release and increase release of the potent anti-inflammatory cytokine, interleukin-10 (IL-10). Given the growing literature supporting that glial proinflammatory cytokines importantly contribute to neuropathic pain and that IL-10 can suppress such pain, we evaluated the effects of intrathecally administered A(2A)R agonists on neuropathic pain using the chronic constriction injury (CCI) model. A single intrathecal injection of the A(2A)R agonists 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl) -9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313) or 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine HCl (CGS21680), 10-14 d after CCI versus sham surgery, produced a long-duration reversal of mechanical allodynia and thermal hyperalgesia for at least 4 weeks. Neither drug altered the nociceptive responses of sham-operated controls. An A(2A)R antagonist [ZM241385 (4-(2-[7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a)(1,3,5)triazin-5-ylamino]e thyl)phenol)] coadministered intrathecally with ATL313 abolished the action of ATL313 in rats with neuropathy-induced allodynia but had no effect on allodynia in the absence of the A(2A)R agonist. ATL313 attenuated CCI-induced upregulation of spinal cord activation markers for microglia and astrocytes in the L4-L6 spinal cord segments both 1 and 4 weeks after a single intrathecal ATL313 administration. Neutralizing IL-10 antibodies administered intrathecally transiently abolished the effect of ATL313 on neuropathic pain. In addition, IL-10 mRNA was significantly elevated in the CSF cells collected from the lumbar region. Activation of A(2A)Rs after intrathecal administration may be a novel, therapeutic approach for the treatment of neuropathic pain by increasing IL-10 in the immunocompetent cells of the CNS.
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Authors: Loram, L. C. - Harrison, J. A. - Sloane, E. M. - Hutchinson, M. R. - Sholar, P. - Taylor, F. R. - Berkelhammer, D. - Coats, B. D. - Poole, S. - Milligan, E. D. - Maier, S. F. - Rieger, J. - Watkins, L. R.
Journal: J Neurosci
Previous studies of peripheral immune cells have documented that activation of adenosine 2A receptors (A(2A)Rs) decrease proinflammatory cytokine release and increase release of the potent anti-inflammatory cytokine, interleukin-10 (IL-10). Given the growing literature supporting that glial proinflammatory cytokines importantly contribute to neuropathic pain and that IL-10 can suppress such pain, we evaluated the effects of intrathecally administered A(2A)R agonists on neuropathic pain using the chronic constriction injury (CCI) model. A single intrathecal injection of the A(2A)R agonists 4-(3-(6-amino-9-(5-cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl) -9H-purin-2-yl)prop-2-ynyl)piperidine-1-carboxylic acid methyl ester (ATL313) or 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido adenosine HCl (CGS21680), 10-14 d after CCI versus sham surgery, produced a long-duration reversal of mechanical allodynia and thermal hyperalgesia for at least 4 weeks. Neither drug altered the nociceptive responses of sham-operated controls. An A(2A)R antagonist [ZM241385 (4-(2-[7-amino-2-(2-furyl)(1,2,4)triazolo(2,3-a)(1,3,5)triazin-5-ylamino]e thyl)phenol)] coadministered intrathecally with ATL313 abolished the action of ATL313 in rats with neuropathy-induced allodynia but had no effect on allodynia in the absence of the A(2A)R agonist. ATL313 attenuated CCI-induced upregulation of spinal cord activation markers for microglia and astrocytes in the L4-L6 spinal cord segments both 1 and 4 weeks after a single intrathecal ATL313 administration. Neutralizing IL-10 antibodies administered intrathecally transiently abolished the effect of ATL313 on neuropathic pain. In addition, IL-10 mRNA was significantly elevated in the CSF cells collected from the lumbar region. Activation of A(2A)Rs after intrathecal administration may be a novel, therapeutic approach for the treatment of neuropathic pain by increasing IL-10 in the immunocompetent cells of the CNS.
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Range-adapting representation of economic value in the orbitofrontal cortex.
Publication Date: 2009 Nov 4 PMID: 19890010
Authors: Padoa-Schioppa, C.
Journal: J Neurosci
While making economic choices, individuals assign subjective values to the available options. Values computed in different behavioral conditions, however, can vary substantially. The same person might choose some times between goods worth a few dollars, and other times between goods worth thousands of dollars, or more. How does the brain system that computes values -- the "valuation system" -- handle this large variability? Here we show that the representation of value in the orbitofrontal cortex (OFC), an area implicated in value assignment during economic choice, adapts to the behavioral condition of choice and, more specifically, to the range of values available in any given condition. In the experiments, monkeys chose between different juices and their choice patterns provided a measure of subjective value. Value ranges were varied from session to session and, in each session, OFC neurons encoded values in a linear way. Across the population, the neuronal sensitivity (defined as the change in neuronal activity elicited by the increase in one value unit) was inversely proportional to the value range. Conversely, the neuronal activity range did not depend on the value range. This phenomenon of range adaptation complements that of menu invariance observed in a previous study. Indeed, the activity of each neuron adapts to the range values it encodes but does not depend on other available goods. Our results thus suggest that the representation of value in the OFC is at one time instantiative of preference transitivity (menu invariance) and computationally efficient (range adaptation).
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Authors: Padoa-Schioppa, C.
Journal: J Neurosci
While making economic choices, individuals assign subjective values to the available options. Values computed in different behavioral conditions, however, can vary substantially. The same person might choose some times between goods worth a few dollars, and other times between goods worth thousands of dollars, or more. How does the brain system that computes values -- the "valuation system" -- handle this large variability? Here we show that the representation of value in the orbitofrontal cortex (OFC), an area implicated in value assignment during economic choice, adapts to the behavioral condition of choice and, more specifically, to the range of values available in any given condition. In the experiments, monkeys chose between different juices and their choice patterns provided a measure of subjective value. Value ranges were varied from session to session and, in each session, OFC neurons encoded values in a linear way. Across the population, the neuronal sensitivity (defined as the change in neuronal activity elicited by the increase in one value unit) was inversely proportional to the value range. Conversely, the neuronal activity range did not depend on the value range. This phenomenon of range adaptation complements that of menu invariance observed in a previous study. Indeed, the activity of each neuron adapts to the range values it encodes but does not depend on other available goods. Our results thus suggest that the representation of value in the OFC is at one time instantiative of preference transitivity (menu invariance) and computationally efficient (range adaptation).
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More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory.
Publication Date: 2009 Nov 2 PMID: 19889466
Authors: Mozzachiodi, R. - Byrne, J. H.
Journal: Trends Neurosci
Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit is set to a permissive state to facilitate synaptic modifications that are necessary for memory storage.
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Authors: Mozzachiodi, R. - Byrne, J. H.
Journal: Trends Neurosci
Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit is set to a permissive state to facilitate synaptic modifications that are necessary for memory storage.
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Molecular layers underlying cytoskeletal remodelling during cortical development.
Publication Date: 2009 Oct 16 PMID: 19837469
Authors: Heng, J. I. - Chariot, A. - Nguyen, L.
Journal: Trends Neurosci
During neural development, the cytoskeleton of newborn neurons undergoes extensive and dynamic remodelling to facilitate the sequential steps of neurogenesis, cell migration and terminal differentiation. It is clear from studying the mechanisms that precipitate these functions that different configurations of the cytoskeleton prefigure the correct execution of each step and define cohorts of proteins the functions of which are indispensable for the control of neuronal migration but not terminal differentiation. These combinatorial protein functions are also predetermined by regulated gene expression and the precise subcellular localisation of their protein products. Here, we expand on this view in the context of recent data on how the cytoskeleton is regulated during the maturation of cortical neurons within the developing brain.
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Authors: Heng, J. I. - Chariot, A. - Nguyen, L.
Journal: Trends Neurosci
During neural development, the cytoskeleton of newborn neurons undergoes extensive and dynamic remodelling to facilitate the sequential steps of neurogenesis, cell migration and terminal differentiation. It is clear from studying the mechanisms that precipitate these functions that different configurations of the cytoskeleton prefigure the correct execution of each step and define cohorts of proteins the functions of which are indispensable for the control of neuronal migration but not terminal differentiation. These combinatorial protein functions are also predetermined by regulated gene expression and the precise subcellular localisation of their protein products. Here, we expand on this view in the context of recent data on how the cytoskeleton is regulated during the maturation of cortical neurons within the developing brain.
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The neural basis of the speed-accuracy tradeoff.
Publication Date: 2009 Oct 8 PMID: 19819033
Authors: Bogacz, R. - Wagenmakers, E. J. - Forstmann, B. U. - Nieuwenhuis, S.
Journal: Trends Neurosci
In many situations, decision makers need to negotiate between the competing demands of response speed and response accuracy, a dilemma generally known as the speed-accuracy tradeoff (SAT). Despite the ubiquity of SAT, the question of how neural decision circuits implement SAT has received little attention up until a year ago. We review recent studies that show SAT is modulated in association and pre-motor areas rather than in sensory or primary motor areas. Furthermore, the studies suggest that emphasis on response speed increases the baseline firing rate of cortical integrator neurons. We also review current theories on how and where in the brain the SAT is controlled, and we end by proposing research directions that could distinguish between these theories.
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Authors: Bogacz, R. - Wagenmakers, E. J. - Forstmann, B. U. - Nieuwenhuis, S.
Journal: Trends Neurosci
In many situations, decision makers need to negotiate between the competing demands of response speed and response accuracy, a dilemma generally known as the speed-accuracy tradeoff (SAT). Despite the ubiquity of SAT, the question of how neural decision circuits implement SAT has received little attention up until a year ago. We review recent studies that show SAT is modulated in association and pre-motor areas rather than in sensory or primary motor areas. Furthermore, the studies suggest that emphasis on response speed increases the baseline firing rate of cortical integrator neurons. We also review current theories on how and where in the brain the SAT is controlled, and we end by proposing research directions that could distinguish between these theories.
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Making a neuron: Cdk5 in embryonic and adult neurogenesis.
Publication Date: 2009 Nov PMID: 19782409
Authors: Jessberger, S. - Gage, F. H. - Eisch, A. J. - Lagace, D. C.
Journal: Trends Neurosci
Cyclin-dependent kinase 5 (Cdk5) has been implicated in the migration, maturation and survival of neurons born during embryonic development. New evidence suggests that Cdk5 has comparable but also distinct functions in adult neurogenesis. Here we summarize accumulating evidence on the role of Cdk5 in regulation of the cell cycle, migration, survival, maturation and neuronal integration. We specifically highlight the many similarities and few tantalizing differences in the roles of Cdk5 in the embryonic and adult brain. We discuss the signaling pathways that might contribute to Cdk5 action in regulating embryonic and adult neurogenesis, highlighting future research directions that will help to clarify the mechanisms underlying lifelong neurogenesis in the mammalian brain.
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Authors: Jessberger, S. - Gage, F. H. - Eisch, A. J. - Lagace, D. C.
Journal: Trends Neurosci
Cyclin-dependent kinase 5 (Cdk5) has been implicated in the migration, maturation and survival of neurons born during embryonic development. New evidence suggests that Cdk5 has comparable but also distinct functions in adult neurogenesis. Here we summarize accumulating evidence on the role of Cdk5 in regulation of the cell cycle, migration, survival, maturation and neuronal integration. We specifically highlight the many similarities and few tantalizing differences in the roles of Cdk5 in the embryonic and adult brain. We discuss the signaling pathways that might contribute to Cdk5 action in regulating embryonic and adult neurogenesis, highlighting future research directions that will help to clarify the mechanisms underlying lifelong neurogenesis in the mammalian brain.
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Cingulate cortex: diverging data from humans and monkeys.
Publication Date: 2009 Nov PMID: 19781794
Authors: Cole, M. W. - Yeung, N. - Freiwald, W. A. - Botvinick, M.
Journal: Trends Neurosci
Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of distinguishing illusory cross-species differences from the true evolutionary differences that make our species unique.
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Authors: Cole, M. W. - Yeung, N. - Freiwald, W. A. - Botvinick, M.
Journal: Trends Neurosci
Cognitive neuroscience research relies, in part, on homologies between the brains of human and non-human primates. A quandary therefore arises when presumed anatomical homologues exhibit different functional properties. Such a situation has recently arisen in the case of the anterior cingulate cortex (ACC). In humans, numerous studies suggest a role for ACC in detecting conflicts in information processing. Studies of macaque monkey ACC, in contrast, have failed to find conflict-related responses. We consider several interpretations of this discrepancy, including differences in research methodology and cross-species differences in functional neuroanatomy. New directions for future research are outlined, emphasizing the importance of distinguishing illusory cross-species differences from the true evolutionary differences that make our species unique.
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Multiple roles of HDAC inhibition in neurodegenerative conditions.
Publication Date: 2009 Nov PMID: 19775759
Authors: Chuang, D. M. - Leng, Y. - Marinova, Z. - Kim, H. J. - Chiu, C. T.
Journal: Trends Neurosci
Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders.
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Authors: Chuang, D. M. - Leng, Y. - Marinova, Z. - Kim, H. J. - Chiu, C. T.
Journal: Trends Neurosci
Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders.
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Squelching glioblastoma stem cells by targeting REST for proteasomal degradation.
Publication Date: 2009 Nov PMID: 19748686
Authors: Zhang, P. - Lathia, J. D. - Flavahan, W. A. - Rich, J. N. - Mattson, M. P.
Journal: Trends Neurosci
Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFbeta-TrCP. Reduced TRF2 binding to REST, and increased SCFbeta-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because postmitotic neurons do not express REST and have relatively stable telomeres.
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Authors: Zhang, P. - Lathia, J. D. - Flavahan, W. A. - Rich, J. N. - Mattson, M. P.
Journal: Trends Neurosci
Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCFbeta-TrCP. Reduced TRF2 binding to REST, and increased SCFbeta-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because postmitotic neurons do not express REST and have relatively stable telomeres.
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Visual processing, learning and feedback in the primate eye movement system.
Publication Date: 2009 Nov PMID: 19729211
Authors: Trommershauser, J. - Glimcher, P. W. - Gegenfurtner, K. R.
Journal: Trends Neurosci
We present an overview of recent paradigms used for studying visual information and reward processing in the human and monkey oculomotor pathways. Current evidence indicates that eye movements made during visual search tasks rely on neural computations similar to those employed when eye movements are planned and executed to obtain explicit rewards. These data suggest that human eye movements originate from the processing of (predominantly visual) sensory information, feedback about previous errors, and expectations about factors, such as reward. We conclude that these properties make the saccadic system an ideal model for studying both the behavioral and neural mechanisms for human voluntary and involuntary choice behavior.
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Authors: Trommershauser, J. - Glimcher, P. W. - Gegenfurtner, K. R.
Journal: Trends Neurosci
We present an overview of recent paradigms used for studying visual information and reward processing in the human and monkey oculomotor pathways. Current evidence indicates that eye movements made during visual search tasks rely on neural computations similar to those employed when eye movements are planned and executed to obtain explicit rewards. These data suggest that human eye movements originate from the processing of (predominantly visual) sensory information, feedback about previous errors, and expectations about factors, such as reward. We conclude that these properties make the saccadic system an ideal model for studying both the behavioral and neural mechanisms for human voluntary and involuntary choice behavior.
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Decoding and reconstructing color from responses in human visual cortex.
Publication Date: 2009 Nov 4 PMID: 19890009
Authors: Brouwer, G. J. - Heeger, D. J.
Journal: J Neurosci
How is color represented by spatially distributed patterns of activity in visual cortex? Functional magnetic resonance imaging responses to several stimulus colors were analyzed with multivariate techniques: conventional pattern classification, a forward model of idealized color tuning, and principal component analysis (PCA). Stimulus color was accurately decoded from activity in V1, V2, V3, V4, and VO1 but not LO1, LO2, V3A/B, or MT+. The conventional classifier and forward model yielded similar accuracies, but the forward model (unlike the classifier) also reliably reconstructed novel stimulus colors not used to train (specify parameters of) the model. The mean responses, averaged across voxels in each visual area, were not reliably distinguishable for the different stimulus colors. Hence, each stimulus color was associated with a unique spatially distributed pattern of activity, presumably reflecting the color selectivity of cortical neurons. Using PCA, a color space was derived from the covariation, across voxels, in the responses to different colors. In V4 and VO1, the first two principal component scores (main source of variation) of the responses revealed a progression through perceptual color space, with perceptually similar colors evoking the most similar responses. This was not the case for any of the other visual cortical areas, including V1, although decoding was most accurate in V1. This dissociation implies a transformation from the color representation in V1 to reflect perceptual color space in V4 and VO1.
post to: CiteULike
Authors: Brouwer, G. J. - Heeger, D. J.
Journal: J Neurosci
How is color represented by spatially distributed patterns of activity in visual cortex? Functional magnetic resonance imaging responses to several stimulus colors were analyzed with multivariate techniques: conventional pattern classification, a forward model of idealized color tuning, and principal component analysis (PCA). Stimulus color was accurately decoded from activity in V1, V2, V3, V4, and VO1 but not LO1, LO2, V3A/B, or MT+. The conventional classifier and forward model yielded similar accuracies, but the forward model (unlike the classifier) also reliably reconstructed novel stimulus colors not used to train (specify parameters of) the model. The mean responses, averaged across voxels in each visual area, were not reliably distinguishable for the different stimulus colors. Hence, each stimulus color was associated with a unique spatially distributed pattern of activity, presumably reflecting the color selectivity of cortical neurons. Using PCA, a color space was derived from the covariation, across voxels, in the responses to different colors. In V4 and VO1, the first two principal component scores (main source of variation) of the responses revealed a progression through perceptual color space, with perceptually similar colors evoking the most similar responses. This was not the case for any of the other visual cortical areas, including V1, although decoding was most accurate in V1. This dissociation implies a transformation from the color representation in V1 to reflect perceptual color space in V4 and VO1.
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Retinotopic mapping requires focal adhesion kinase-mediated regulation of growth cone adhesion.
Publication Date: 2009 Nov 4 PMID: 19890008
Authors: Woo, S. - Rowan, D. J. - Gomez, T. M.
Journal: J Neurosci
Adhesion controls growth cone motility, yet the effects of axon guidance cues on adhesion site dynamics are poorly understood. Here we show that ephrin-A1 reduces retinal ganglion cell (RGC) axon outgrowth by stabilizing existing adhesions and inhibiting new adhesion assembly. Ephrin-A1 activates focal adhesion kinase (FAK) in an integrin- and Src-dependent manner and the effects of ephrin-A1 on growth cone motility require FAK activation. We also find that FAK is expressed in a high temporal to low nasal gradient in RGCs, similar to EphA receptors, and that balanced FAK activation is necessary for optimal axon outgrowth. Last, we find that FAK is required for proper topographic positioning of retinal axons along the anterior-posterior axis of the optic tectum in both Xenopus and zebrafish, a guidance decision mediated in part by A-type ephrins. Together, our data suggest that ephrin-A1 controls growth cone advance by modulating adhesive point contacts through FAK activation and that graded FAK signaling is an important component of ephrin-A-mediated retinotopic mapping.
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Authors: Woo, S. - Rowan, D. J. - Gomez, T. M.
Journal: J Neurosci
Adhesion controls growth cone motility, yet the effects of axon guidance cues on adhesion site dynamics are poorly understood. Here we show that ephrin-A1 reduces retinal ganglion cell (RGC) axon outgrowth by stabilizing existing adhesions and inhibiting new adhesion assembly. Ephrin-A1 activates focal adhesion kinase (FAK) in an integrin- and Src-dependent manner and the effects of ephrin-A1 on growth cone motility require FAK activation. We also find that FAK is expressed in a high temporal to low nasal gradient in RGCs, similar to EphA receptors, and that balanced FAK activation is necessary for optimal axon outgrowth. Last, we find that FAK is required for proper topographic positioning of retinal axons along the anterior-posterior axis of the optic tectum in both Xenopus and zebrafish, a guidance decision mediated in part by A-type ephrins. Together, our data suggest that ephrin-A1 controls growth cone advance by modulating adhesive point contacts through FAK activation and that graded FAK signaling is an important component of ephrin-A-mediated retinotopic mapping.
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Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis.
Publication Date: 2009 Nov 4 PMID: 19890007
Authors: Parisiadou, L. - Xie, C. - Cho, H. J. - Lin, X. - Gu, X. L. - Long, C. X. - Lobbestael, E. - Baekelandt, V. - Taymans, J. M. - Sun, L. - Cai, H.
Journal: J Neurosci
Leucine-rich repeat kinase 2 (LRRK2) functions as a putative protein kinase of ezrin, radixin, and moesin (ERM) family proteins. A Parkinson's disease-related G2019S substitution in the kinase domain of LRRK2 further enhances the phosphorylation of ERM proteins. The phosphorylated ERM (pERM) proteins are restricted to the filopodia of growing neurites in which they tether filamentous actin (F-actin) to the cytoplasmic membrane and regulate the dynamics of filopodia protrusion. Here, we show that, in cultured neurons derived from LRRK2 G2019S transgenic mice, the number of pERM-positive and F-actin-enriched filopodia was significantly increased, and this correlates with the retardation of neurite outgrowth. Conversely, deletion of LRRK2, which lowered the pERM and F-actin contents in filopodia, promoted neurite outgrowth. Furthermore, inhibition of ERM phosphorylation or actin polymerization rescued the G2019S-dependent neuronal growth defects. These data support a model in which the G2019S mutation of LRRK2 causes a gain-of-function effect that perturbs the homeostasis of pERM and F-actin in sprouting neurites critical for neuronal morphogenesis.
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Authors: Parisiadou, L. - Xie, C. - Cho, H. J. - Lin, X. - Gu, X. L. - Long, C. X. - Lobbestael, E. - Baekelandt, V. - Taymans, J. M. - Sun, L. - Cai, H.
Journal: J Neurosci
Leucine-rich repeat kinase 2 (LRRK2) functions as a putative protein kinase of ezrin, radixin, and moesin (ERM) family proteins. A Parkinson's disease-related G2019S substitution in the kinase domain of LRRK2 further enhances the phosphorylation of ERM proteins. The phosphorylated ERM (pERM) proteins are restricted to the filopodia of growing neurites in which they tether filamentous actin (F-actin) to the cytoplasmic membrane and regulate the dynamics of filopodia protrusion. Here, we show that, in cultured neurons derived from LRRK2 G2019S transgenic mice, the number of pERM-positive and F-actin-enriched filopodia was significantly increased, and this correlates with the retardation of neurite outgrowth. Conversely, deletion of LRRK2, which lowered the pERM and F-actin contents in filopodia, promoted neurite outgrowth. Furthermore, inhibition of ERM phosphorylation or actin polymerization rescued the G2019S-dependent neuronal growth defects. These data support a model in which the G2019S mutation of LRRK2 causes a gain-of-function effect that perturbs the homeostasis of pERM and F-actin in sprouting neurites critical for neuronal morphogenesis.
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Stimulus-induced and state-dependent sustained gamma activity is tightly coupled to the hemodynamic response in humans.
Publication Date: 2009 Nov 4 PMID: 19890006
Authors: Koch, S. P. - Werner, P. - Steinbrink, J. - Fries, P. - Obrig, H.
Journal: J Neurosci
A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.
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Authors: Koch, S. P. - Werner, P. - Steinbrink, J. - Fries, P. - Obrig, H.
Journal: J Neurosci
A prompt behavioral response to a stimulus depends both on the salience of the stimulus as well as the subject's preparedness. Thus, both stimulus properties and cognitive factors, such as attention, may determine the strength of neuronal synchronization in the gamma range. For a comprehensive investigation of stimulus-response processing through noninvasive imaging, it is, however, a crucial issue whether both kinds of gamma modulation elicit a hemodynamic response. Here, we show that, in the human visual cortex, stimulus strength and internal state modulate sustained gamma activity and hemodynamic response in close correspondence. When participants reported velocity changes of gratings varying in contrast, gamma activity (35-70 Hz) increased systematically with contrast. For stimuli of constant contrast, the amplitude of gamma activity before the behaviorally relevant velocity change was inversely correlated to the behavioral response latency. This indicates that gamma activity also reflects an overall attentive state. For both sources of variance, gamma activity was tightly coupled to the hemodynamic response measured through optical topography. Because of the close relationship between high-frequency neuronal activity and the hemodynamic signal, we conclude that both stimulus-induced and state-dependent gamma activity trigger a metabolic demand and are amenable to vascular-based imaging.
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Decreased firing of striatal neurons related to licking during acquisition and overtraining of a licking task.
Publication Date: 2009 Nov 4 PMID: 19890005
Authors: Tang, C. C. - Root, D. H. - Duke, D. C. - Zhu, Y. - Teixeria, K. - Ma, S. - Barker, D. J. - West, M. O.
Journal: J Neurosci
Neurons that fire in relation to licking, in the ventral part of the dorsolateral striatum (DLS), were studied during acquisition and performance of a licking task in rats for 14 sessions (2 h/d). Task learning was indicated by fewer errors of omission of licking and improved movement efficiency (i.e., shorter lick duration) over sessions. Number of licks did not change over sessions. Overtraining did not result in habit formation, as indicated by similar reductions of licking responses following devaluation by satiety in both early and late sessions. Twenty-nine lick neurons recorded and tracked over sessions exhibited a significant linear decrease in average firing rate across all neurons over sessions, correlating with concurrent declines in lick duration. Individually, most neurons (86%) exhibited decreased firing rates, while a small proportion (14%) exhibited increased firing rates, during lick movements that were matched over sessions. Reward manipulations did not alter firing patterns over sessions. Aside from the absence of habit formation, striatal processing during unconditioned movements (i.e., licking) was characterized by high activity of movement-related neurons during early performance and decreased activity of the same neurons during overtraining, similar to our previous report of head movement neurons during acquired, skilled, instrumental head movements that ultimately became habitual (Tang et al., 2007). Decreased activity in DLS neurons may reflect a common neural mechanism underlying improvement in movement efficiency with overtraining. Nonetheless, the decreased striatal firing in relation to a movement that did not become habitual demonstrates that not all DLS changes reflect habit formation.
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Authors: Tang, C. C. - Root, D. H. - Duke, D. C. - Zhu, Y. - Teixeria, K. - Ma, S. - Barker, D. J. - West, M. O.
Journal: J Neurosci
Neurons that fire in relation to licking, in the ventral part of the dorsolateral striatum (DLS), were studied during acquisition and performance of a licking task in rats for 14 sessions (2 h/d). Task learning was indicated by fewer errors of omission of licking and improved movement efficiency (i.e., shorter lick duration) over sessions. Number of licks did not change over sessions. Overtraining did not result in habit formation, as indicated by similar reductions of licking responses following devaluation by satiety in both early and late sessions. Twenty-nine lick neurons recorded and tracked over sessions exhibited a significant linear decrease in average firing rate across all neurons over sessions, correlating with concurrent declines in lick duration. Individually, most neurons (86%) exhibited decreased firing rates, while a small proportion (14%) exhibited increased firing rates, during lick movements that were matched over sessions. Reward manipulations did not alter firing patterns over sessions. Aside from the absence of habit formation, striatal processing during unconditioned movements (i.e., licking) was characterized by high activity of movement-related neurons during early performance and decreased activity of the same neurons during overtraining, similar to our previous report of head movement neurons during acquired, skilled, instrumental head movements that ultimately became habitual (Tang et al., 2007). Decreased activity in DLS neurons may reflect a common neural mechanism underlying improvement in movement efficiency with overtraining. Nonetheless, the decreased striatal firing in relation to a movement that did not become habitual demonstrates that not all DLS changes reflect habit formation.
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