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Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex: analysis of matrix metalloproteinase 9 deficient mice.

Kelly EA, Russo AS, Jackson CD, Lamantia CE, Majewska AK - Front Cell Neurosci (2015)

Bottom Line: Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex.We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity.Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9.

View Article: PubMed Central - PubMed

Affiliation: Center for Visual Science, School of Medicine and Dentistry, Department of Neurobiology and Anatomy, University of Rochester Rochester, NY, USA.

ABSTRACT
The extracellular matrix (ECM) is known to play important roles in regulating neuronal recovery from injury. The ECM can also impact physiological synaptic plasticity, although this process is less well understood. To understand the impact of the ECM on synaptic function and remodeling in vivo, we examined ECM composition and proteolysis in a well-established model of experience-dependent plasticity in the visual cortex. We describe a rapid change in ECM protein composition during Ocular Dominance Plasticity (ODP) in adolescent mice, and a loss of ECM remodeling in mice that lack the extracellular protease, matrix metalloproteinase-9 (MMP9). Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex. While we observed no change in the morphology of existing dendritic spines, spine dynamics were altered, and MMP9 knock-out (KO) mice showed increased turnover of dendritic spines over a period of 2 days. We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity. MMP9 KO mice exhibited very limited changes in microglial morphology. Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9. Taken together, our results show that MMP9 contributes to ECM degradation, synaptic dynamics and sensory-evoked plasticity in the mouse visual cortex.

No MeSH data available.


Related in: MedlinePlus

CSPGs composition comparisons between WT and matrix metalloproteinase 9 (MMP9) knock-out (KO) mice. (A–D) Quantitative analysis of PNN intensity, Neuropil intensity, PNN size, and PNN density between WT and MMP9 KO ND mice showing few differences between the ND conditions. Significant decreases were noted in MMP9 KO mice in L5 of PNN intensity, PNN size and PNN density suggesting a laminar effect of MMP9 depletion. Statistics = Two-way ANOVA with Bonferroni multiple comparisons post hoc analysis. All values reported are the mean ± SEM. *p < 0.05.
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Figure 3: CSPGs composition comparisons between WT and matrix metalloproteinase 9 (MMP9) knock-out (KO) mice. (A–D) Quantitative analysis of PNN intensity, Neuropil intensity, PNN size, and PNN density between WT and MMP9 KO ND mice showing few differences between the ND conditions. Significant decreases were noted in MMP9 KO mice in L5 of PNN intensity, PNN size and PNN density suggesting a laminar effect of MMP9 depletion. Statistics = Two-way ANOVA with Bonferroni multiple comparisons post hoc analysis. All values reported are the mean ± SEM. *p < 0.05.

Mentions: For laminar determination, alternating sections were counterstained with a 0.5% Cresyl violet (CV) Acetate stain (1% CV in dH2O in an acetate buffer [9:1 ratio of acidic component (0.6% Glacial acetic acid in dH2O) to basic component (1.36% sodium acetate in dH2O)]. ECM analysis was performed in individual layers (2/3, 4, and 6). Determination of layer was performed based on cellular size and density by an experienced observer using neighboring sections stained with CV. The distinct cytological architecture allowed high magnified image collection at the vertical center of each layer. Layer 2/3 (the external pyramidal layer) contains predominantly small and medium sized pyramidal neurons. Layer 4 (the internal granular layer) contains different types of smaller stellate and pyramidal neurons, providing an obvious cytological transition from L2/3 and a definitive border with L5. L5 (the internal pyramidal layer), contains large pyramidal neurons while L6 (the polymorphic or multiform layer) contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons. (Mountcastle, 1997) For examples see Figures 1A,F, 2A, 4A.


Proteolytic regulation of synaptic plasticity in the mouse primary visual cortex: analysis of matrix metalloproteinase 9 deficient mice.

Kelly EA, Russo AS, Jackson CD, Lamantia CE, Majewska AK - Front Cell Neurosci (2015)

CSPGs composition comparisons between WT and matrix metalloproteinase 9 (MMP9) knock-out (KO) mice. (A–D) Quantitative analysis of PNN intensity, Neuropil intensity, PNN size, and PNN density between WT and MMP9 KO ND mice showing few differences between the ND conditions. Significant decreases were noted in MMP9 KO mice in L5 of PNN intensity, PNN size and PNN density suggesting a laminar effect of MMP9 depletion. Statistics = Two-way ANOVA with Bonferroni multiple comparisons post hoc analysis. All values reported are the mean ± SEM. *p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Figure 3: CSPGs composition comparisons between WT and matrix metalloproteinase 9 (MMP9) knock-out (KO) mice. (A–D) Quantitative analysis of PNN intensity, Neuropil intensity, PNN size, and PNN density between WT and MMP9 KO ND mice showing few differences between the ND conditions. Significant decreases were noted in MMP9 KO mice in L5 of PNN intensity, PNN size and PNN density suggesting a laminar effect of MMP9 depletion. Statistics = Two-way ANOVA with Bonferroni multiple comparisons post hoc analysis. All values reported are the mean ± SEM. *p < 0.05.
Mentions: For laminar determination, alternating sections were counterstained with a 0.5% Cresyl violet (CV) Acetate stain (1% CV in dH2O in an acetate buffer [9:1 ratio of acidic component (0.6% Glacial acetic acid in dH2O) to basic component (1.36% sodium acetate in dH2O)]. ECM analysis was performed in individual layers (2/3, 4, and 6). Determination of layer was performed based on cellular size and density by an experienced observer using neighboring sections stained with CV. The distinct cytological architecture allowed high magnified image collection at the vertical center of each layer. Layer 2/3 (the external pyramidal layer) contains predominantly small and medium sized pyramidal neurons. Layer 4 (the internal granular layer) contains different types of smaller stellate and pyramidal neurons, providing an obvious cytological transition from L2/3 and a definitive border with L5. L5 (the internal pyramidal layer), contains large pyramidal neurons while L6 (the polymorphic or multiform layer) contains few large pyramidal neurons and many small spindle-like pyramidal and multiform neurons. (Mountcastle, 1997) For examples see Figures 1A,F, 2A, 4A.

Bottom Line: Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex.We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity.Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9.

View Article: PubMed Central - PubMed

Affiliation: Center for Visual Science, School of Medicine and Dentistry, Department of Neurobiology and Anatomy, University of Rochester Rochester, NY, USA.

ABSTRACT
The extracellular matrix (ECM) is known to play important roles in regulating neuronal recovery from injury. The ECM can also impact physiological synaptic plasticity, although this process is less well understood. To understand the impact of the ECM on synaptic function and remodeling in vivo, we examined ECM composition and proteolysis in a well-established model of experience-dependent plasticity in the visual cortex. We describe a rapid change in ECM protein composition during Ocular Dominance Plasticity (ODP) in adolescent mice, and a loss of ECM remodeling in mice that lack the extracellular protease, matrix metalloproteinase-9 (MMP9). Loss of MMP9 also attenuated functional ODP following monocular deprivation (MD) and reduced excitatory synapse density and spine density in sensory cortex. While we observed no change in the morphology of existing dendritic spines, spine dynamics were altered, and MMP9 knock-out (KO) mice showed increased turnover of dendritic spines over a period of 2 days. We also analyzed the effects of MMP9 loss on microglia, as these cells are involved in extracellular remodeling and have been recently shown to be important for synaptic plasticity. MMP9 KO mice exhibited very limited changes in microglial morphology. Ultrastructural analysis, however, showed that the extracellular space surrounding microglia was increased, with concomitant increases in microglial inclusions, suggesting possible changes in microglial function in the absence of MMP9. Taken together, our results show that MMP9 contributes to ECM degradation, synaptic dynamics and sensory-evoked plasticity in the mouse visual cortex.

No MeSH data available.


Related in: MedlinePlus