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RGMa inhibition enhances synapse formation of the cortico-spinal axons after spinal cord injury
S190
Abstracts / Neuroscience Research 58S (2007) S1–S244
9 Activation of presynaptically silent synapses—One of P3-b0 underlying mechanisms enhancing mossy fiber transmission in the hippocampus
P3-b12 Trapping of the Vesl-1S protein into dendritic spines is input-specific
1
Daisuke Okada 1 , Fumiko Ozawa 1 , Kaoru Inokuchi 1,2 1 Mitsubishi Kagaku Inst Life Sciences, Machida, Japan; JST, Japan
The activation of presynaptically silent synapses is hypothesized to be one of mechanisms of the synaptic enhancement. This hypothesis was tested for the PKC-dependent enhancement of mossy fiber (MF)-CA3 synaptic transmission in the hippocampus. Individual large MF boutons were identified in the acute slice of hippocampus and the activity-dependent changes of synaptopHluorin were measured. We found that the individual MF boutons are variably responsive to PKC. Among them some presynaptically silent boutons became active. The individual MF bouton consists of dozens of active zones. It is possible that each active zone has at least two states, releasable and non-releasable. These MF boutons may have mostly non-releasable active zones which become releasable by a PKC-dependent mechanism. All animal procedures were conducted in accordance with the guiding principles of NIH.
Input-specificity of late-phase plasticity involves yet-unknown mechanisms that permit somatically synthesized plasticity-related proteins (PRPs) to function locally in the activated synapses. Although synaptic tagging hypothesis has been proposed to solve this central problem, molecular identity of the tag, signals that tag a synapse and PRPs that substantiate the hypothesis are not known. We hypothesized that the regulated entry of PRPs into dendritic spines works as a synaptic tag. We previously reported that entry of Vesl-1S (Homer 1a)-EGFP (VE) proteins into spines of rat hippocampal neurons in culture was regulated by preand postsynaptic activities, and fulfilled some standards of synaptic tag. Here we applied microperfusion techniques to test whether VE trapping is input-specific. NMDA receptors in limited numbers of spines within a diameter of 10 micrometers were stimulated by microperfusion, which activated VE trapping only in the stimulated area. These results further supported that VE trapping works as a synaptic tag.
Research funds: KAKENHI (17659061), Novartis Foundation Japan, Suzuken Memorial Foundation
Research funds: Special Coordinate Funds for Promoting Science and Technology, MEXT
P3-b10 cAMP signaling cascade is reduced in hippocampal
P3-b13 Proteolytic cleavage of telencephalin by plasmin in
Takuya Hikima 1 , Rikita Araki 2 , Toru Ishizuka 1 , Hiromu Yawo 1 Dept of Dev Biol and Neurosci, Tohoku Univ Grad Sch of Life Sci, Sendai, Japan; 2 Laboratory for Neuronal Circuit Daynamics, BSI, RIKEN, Wako-shi, Japan
LTP of HPC-1/syntaxin 1A knock-out mice Mishima 1 ,
Fujiwara 1 ,
Kofuji 2 ,
Tatsuya Tomonori Takefumi Kimio Akagawa 1 1 Department of Cell Physiology, Kyorin University School of Medicine, Tokyo, Japan; 2 Division of Radioisotope Research, Kyorin University School of Medicine, Tokyo, Japan
2
CREST,
mouse visual cortex
Nobuko Mataga 1 , James Poyer 1 , Kensaku Mori 3 , Yoshihiro Yoshihara 2,4 , Takao K. Hensch 1,4 1 Neuronal Circuit Dev., Japan; 2 Neurobiol. Synapse, RIKEN BSI, Saitama, Japan; 3 University Tokyo, Japan; 4 CREST, JST, Osaka, Japan
The membrane protein HPC-1/syntaxin 1A believed to plays a key role in synaptic vesicle exocytosis. Previously we reported that HPC-1/syntaxin 1A knock-out mice had impaired learning and behavioral abnormality which was recovered by administration of serotonin selective reuptake inhibitor. Moreover, although the properties of basic synaptic transmission of the matured hippocampal neurons in vitro was normal, the knock-out mice exhibit impairment in induction of long-lasting potentiation in the CA1 of hippocampal slice. In this study, we examined the effect of several agents which affect signal transudation pathways mediating LTP in the CA1. Among them the adenylyl cyclase activator forskolin rescued this impairment of LTP in knock-out mice. This result suggests that cAMP/protein kinase A signaling cascade may be disturbed in LTP of knock-out mice.
Ocular dominance (OD) plasticity reflects a transient loss of dendritic spines in the binocular zone of mouse visual cortex (VC) mediated by tissue-type plasminogen activator (tPA) (Mataga et al., 2004), whose molecular substrates remain unknown. The cell adhesion molecule, telencephalin (TLCN), is a negative regulator of spine maturation (Matsuno et al., 2006) and contributes to hippocampal plasticity (Nakamura et al., 2001). Here, we examined tPA-mediated proteolysis of TLCN as a potential substrate in the VC. TLCN expression emerged before eye-opening and independent of sensory experience. Partial proteolytic cleavage of TLCN was observed in vitro in a dose- and time-dependent manner by plasmin, but not by tPA alone or in the presence of serine protease inhibitor, aprotinin. TLCN was more sensitive to plasmin-dependent proteolysis than another candidate substrate, NCAM. Abnormal accumulation of TLCN was seen in tPA KO beyond the critical period (>P28). Thus, TLCN may be a site of tPA action during OD plasticity.
P3-b11 RGMa inhibition enhances synapse formation of the
P3-b14
Research funds: RIKEN BSI, KAKENHI
cortico-spinal axons after spinal cord injury Akihiro Kyoto, Toshihide Yamashita Department of Neurobiology, Graduate School of Medicine, University of Chiba, Chiba, Japan Several proteins have been identified as inhibitors of axonal regeneration following injury of the adult vertebrate central nervous system. The repulsive guidance molecule (RGMa) is considered a potent myelinderived neurite outgrowth inhibitor. In rats, RGMa inhibition enhances the growth of injured axons and promotes functional recovery after spinal cord injury (SCI). Here, we demonstrate that RGMa inhibition induces synaptic rearrangements of spared axonal projections after SCI. Intrathecal administration of a function-blocking antibody to RGMa enhances anatomical synapse formation of the cortico-spinal tract in the cervical region of rats with thoracic spinalcord hemisection. These findings suggest that the suppression of synapticre arrangements as well as axon growth inhibition in the adult spinal cord may contribute to the limitation of functional recovery after SCI.
Rapid morphological changes of dendritic spines induced by corticosteroids in rat hippocampus
Yoshimasa Komatsuzaki 1,2,3 , Yasushi Hojo 2,3 , Suguru Kawato 2,3 CHS, Nihon University, Tokyo, Japan; 2 Department of Biophys. & Life Sci., University of Tokyo, Tokyo, Japan; 3 CREST, Bioinfomatics Project, JST, Japan
1
Modulation of hippocampal synaptic plasticity by corticosteroids has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. We investigated the effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor, on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM DEX induced rapid modulation of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1 h. Because the presence of cycloheximide, an inhibitor of protein synthesis, did not suppress the DEX effect, these responses are probably non-genomic and not mediated via slow genetic processes. We further examined the effects of corticosterone, on dendritic spine in hippocampal neurons. We found that corticosterone also significantly increased the density of CA1 dendritic spines and changed the morphology of dendritic spines.
Abstracts / Neuroscience Research 58S (2007) S1–S244
9 Activation of presynaptically silent synapses—One of P3-b0 underlying mechanisms enhancing mossy fiber transmission in the hippocampus
P3-b12 Trapping of the Vesl-1S protein into dendritic spines is input-specific
1
Daisuke Okada 1 , Fumiko Ozawa 1 , Kaoru Inokuchi 1,2 1 Mitsubishi Kagaku Inst Life Sciences, Machida, Japan; JST, Japan
The activation of presynaptically silent synapses is hypothesized to be one of mechanisms of the synaptic enhancement. This hypothesis was tested for the PKC-dependent enhancement of mossy fiber (MF)-CA3 synaptic transmission in the hippocampus. Individual large MF boutons were identified in the acute slice of hippocampus and the activity-dependent changes of synaptopHluorin were measured. We found that the individual MF boutons are variably responsive to PKC. Among them some presynaptically silent boutons became active. The individual MF bouton consists of dozens of active zones. It is possible that each active zone has at least two states, releasable and non-releasable. These MF boutons may have mostly non-releasable active zones which become releasable by a PKC-dependent mechanism. All animal procedures were conducted in accordance with the guiding principles of NIH.
Input-specificity of late-phase plasticity involves yet-unknown mechanisms that permit somatically synthesized plasticity-related proteins (PRPs) to function locally in the activated synapses. Although synaptic tagging hypothesis has been proposed to solve this central problem, molecular identity of the tag, signals that tag a synapse and PRPs that substantiate the hypothesis are not known. We hypothesized that the regulated entry of PRPs into dendritic spines works as a synaptic tag. We previously reported that entry of Vesl-1S (Homer 1a)-EGFP (VE) proteins into spines of rat hippocampal neurons in culture was regulated by preand postsynaptic activities, and fulfilled some standards of synaptic tag. Here we applied microperfusion techniques to test whether VE trapping is input-specific. NMDA receptors in limited numbers of spines within a diameter of 10 micrometers were stimulated by microperfusion, which activated VE trapping only in the stimulated area. These results further supported that VE trapping works as a synaptic tag.
Research funds: KAKENHI (17659061), Novartis Foundation Japan, Suzuken Memorial Foundation
Research funds: Special Coordinate Funds for Promoting Science and Technology, MEXT
P3-b10 cAMP signaling cascade is reduced in hippocampal
P3-b13 Proteolytic cleavage of telencephalin by plasmin in
Takuya Hikima 1 , Rikita Araki 2 , Toru Ishizuka 1 , Hiromu Yawo 1 Dept of Dev Biol and Neurosci, Tohoku Univ Grad Sch of Life Sci, Sendai, Japan; 2 Laboratory for Neuronal Circuit Daynamics, BSI, RIKEN, Wako-shi, Japan
LTP of HPC-1/syntaxin 1A knock-out mice Mishima 1 ,
Fujiwara 1 ,
Kofuji 2 ,
Tatsuya Tomonori Takefumi Kimio Akagawa 1 1 Department of Cell Physiology, Kyorin University School of Medicine, Tokyo, Japan; 2 Division of Radioisotope Research, Kyorin University School of Medicine, Tokyo, Japan
2
CREST,
mouse visual cortex
Nobuko Mataga 1 , James Poyer 1 , Kensaku Mori 3 , Yoshihiro Yoshihara 2,4 , Takao K. Hensch 1,4 1 Neuronal Circuit Dev., Japan; 2 Neurobiol. Synapse, RIKEN BSI, Saitama, Japan; 3 University Tokyo, Japan; 4 CREST, JST, Osaka, Japan
The membrane protein HPC-1/syntaxin 1A believed to plays a key role in synaptic vesicle exocytosis. Previously we reported that HPC-1/syntaxin 1A knock-out mice had impaired learning and behavioral abnormality which was recovered by administration of serotonin selective reuptake inhibitor. Moreover, although the properties of basic synaptic transmission of the matured hippocampal neurons in vitro was normal, the knock-out mice exhibit impairment in induction of long-lasting potentiation in the CA1 of hippocampal slice. In this study, we examined the effect of several agents which affect signal transudation pathways mediating LTP in the CA1. Among them the adenylyl cyclase activator forskolin rescued this impairment of LTP in knock-out mice. This result suggests that cAMP/protein kinase A signaling cascade may be disturbed in LTP of knock-out mice.
Ocular dominance (OD) plasticity reflects a transient loss of dendritic spines in the binocular zone of mouse visual cortex (VC) mediated by tissue-type plasminogen activator (tPA) (Mataga et al., 2004), whose molecular substrates remain unknown. The cell adhesion molecule, telencephalin (TLCN), is a negative regulator of spine maturation (Matsuno et al., 2006) and contributes to hippocampal plasticity (Nakamura et al., 2001). Here, we examined tPA-mediated proteolysis of TLCN as a potential substrate in the VC. TLCN expression emerged before eye-opening and independent of sensory experience. Partial proteolytic cleavage of TLCN was observed in vitro in a dose- and time-dependent manner by plasmin, but not by tPA alone or in the presence of serine protease inhibitor, aprotinin. TLCN was more sensitive to plasmin-dependent proteolysis than another candidate substrate, NCAM. Abnormal accumulation of TLCN was seen in tPA KO beyond the critical period (>P28). Thus, TLCN may be a site of tPA action during OD plasticity.
P3-b11 RGMa inhibition enhances synapse formation of the
P3-b14
Research funds: RIKEN BSI, KAKENHI
cortico-spinal axons after spinal cord injury Akihiro Kyoto, Toshihide Yamashita Department of Neurobiology, Graduate School of Medicine, University of Chiba, Chiba, Japan Several proteins have been identified as inhibitors of axonal regeneration following injury of the adult vertebrate central nervous system. The repulsive guidance molecule (RGMa) is considered a potent myelinderived neurite outgrowth inhibitor. In rats, RGMa inhibition enhances the growth of injured axons and promotes functional recovery after spinal cord injury (SCI). Here, we demonstrate that RGMa inhibition induces synaptic rearrangements of spared axonal projections after SCI. Intrathecal administration of a function-blocking antibody to RGMa enhances anatomical synapse formation of the cortico-spinal tract in the cervical region of rats with thoracic spinalcord hemisection. These findings suggest that the suppression of synapticre arrangements as well as axon growth inhibition in the adult spinal cord may contribute to the limitation of functional recovery after SCI.
Rapid morphological changes of dendritic spines induced by corticosteroids in rat hippocampus
Yoshimasa Komatsuzaki 1,2,3 , Yasushi Hojo 2,3 , Suguru Kawato 2,3 CHS, Nihon University, Tokyo, Japan; 2 Department of Biophys. & Life Sci., University of Tokyo, Tokyo, Japan; 3 CREST, Bioinfomatics Project, JST, Japan
1
Modulation of hippocampal synaptic plasticity by corticosteroids has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. We investigated the effect of dexamethasone (DEX), a specific agonist of glucocorticoid receptor, on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 100 nM DEX induced rapid modulation of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1 h. Because the presence of cycloheximide, an inhibitor of protein synthesis, did not suppress the DEX effect, these responses are probably non-genomic and not mediated via slow genetic processes. We further examined the effects of corticosterone, on dendritic spine in hippocampal neurons. We found that corticosterone also significantly increased the density of CA1 dendritic spines and changed the morphology of dendritic spines.