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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

Ocular dominance plasticity (ODP) is attenuated in MMP9 KO mice. (A–F) Representative examples of visually-evoked amplitude maps measured using intrinsic signal optical imaging (iOS) in control (C57Bl/6) and MMP9 KO mice. (G) Quantitative analysis of ODP comparing changes in the ocular dominance index (ODI). Values above 0 denote an ODI with a contralateral bias, while values below value suggest an ODI with an ipsilateral bias. CTL ND (black bar) have a characteristic and expected contralateral bias that significantly shifts to an ipsilateral bias after both 4dMD (CTL 4dMD, white hatched bar) and 7dMD (CTL 7dMD, white dotted bars). MMP9 KO ND (gray bar) displayed a contralateral bias, similar to CTL ND. Following 4dMD (gray hatched bar), MMP9 KO mice failed to demonstrate an ODP shift. ODP was apparent in MMP9 KO 7dMD (gray dotted bar). Statistics = Two-Way ANOVA with bonferroni multiple comparisons. All values reported are the mean ± SEM. *p < 0.05, **p < 0.001.
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Figure 5: Ocular dominance plasticity (ODP) is attenuated in MMP9 KO mice. (A–F) Representative examples of visually-evoked amplitude maps measured using intrinsic signal optical imaging (iOS) in control (C57Bl/6) and MMP9 KO mice. (G) Quantitative analysis of ODP comparing changes in the ocular dominance index (ODI). Values above 0 denote an ODI with a contralateral bias, while values below value suggest an ODI with an ipsilateral bias. CTL ND (black bar) have a characteristic and expected contralateral bias that significantly shifts to an ipsilateral bias after both 4dMD (CTL 4dMD, white hatched bar) and 7dMD (CTL 7dMD, white dotted bars). MMP9 KO ND (gray bar) displayed a contralateral bias, similar to CTL ND. Following 4dMD (gray hatched bar), MMP9 KO mice failed to demonstrate an ODP shift. ODP was apparent in MMP9 KO 7dMD (gray dotted bar). Statistics = Two-Way ANOVA with bonferroni multiple comparisons. All values reported are the mean ± SEM. *p < 0.05, **p < 0.001.

Mentions: Next we wanted to determine whether MMP9-mediated ECM degradation contributes to functional OD shifts. Therefore we performed intrinsic signal optical imaging (iOS) on control (C57Bl/6; CTL) and MMP9 KO mice following 4 days of monocular deprivation (4dMD) and quantified binocularity by calculating an ODI. An ODI above 0 represent a contralateral bias, while values below 0 represent an ipsilateral bias (Cang et al., 2005). CTL mice showed the expected contralateral bias in the absence of MD (Figures 5A,G, black bar, 0.163 ± 0.03). Following MD, responsiveness shifted from a contralateral to ipsilateral bias (Figures 5B,G, white hatched bar (−0.06 ± 0.06), white dotted bar (−0.07 ± 0.04). Non-deprived MMP9 KO mice also showed a strong contralateral response, with an ODI comparable to CTL ND mice (Figures 5D,G, gray bar, 0.212 ± 0.02). After 4 days of MD, however, ODIs failed to shift towards the ipsilateral eye (Figures 5E,G, gray hatched bar, 0.135 ± 0.04). To determine whether plasticity was reduced or slowed by the absence of MMP9, we repeated the experiment after 7 days of MD. By 7dMD, MMP9 KO mice displayed a significant ipsilateral shift similar to that observed in CTL 7dMD mice (Figures 5C,F,G, gray dotted bar, −0.02 ± 0.04, p < 0.05, two-way ANOVA, Bonferroni multiple comparisons) suggesting that MMP9 deficiency delays the induction or manifestation of ODP.


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)

Ocular dominance plasticity (ODP) is attenuated in MMP9 KO mice. (A–F) Representative examples of visually-evoked amplitude maps measured using intrinsic signal optical imaging (iOS) in control (C57Bl/6) and MMP9 KO mice. (G) Quantitative analysis of ODP comparing changes in the ocular dominance index (ODI). Values above 0 denote an ODI with a contralateral bias, while values below value suggest an ODI with an ipsilateral bias. CTL ND (black bar) have a characteristic and expected contralateral bias that significantly shifts to an ipsilateral bias after both 4dMD (CTL 4dMD, white hatched bar) and 7dMD (CTL 7dMD, white dotted bars). MMP9 KO ND (gray bar) displayed a contralateral bias, similar to CTL ND. Following 4dMD (gray hatched bar), MMP9 KO mice failed to demonstrate an ODP shift. ODP was apparent in MMP9 KO 7dMD (gray dotted bar). Statistics = Two-Way ANOVA with bonferroni multiple comparisons. All values reported are the mean ± SEM. *p < 0.05, **p < 0.001.
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Figure 5: Ocular dominance plasticity (ODP) is attenuated in MMP9 KO mice. (A–F) Representative examples of visually-evoked amplitude maps measured using intrinsic signal optical imaging (iOS) in control (C57Bl/6) and MMP9 KO mice. (G) Quantitative analysis of ODP comparing changes in the ocular dominance index (ODI). Values above 0 denote an ODI with a contralateral bias, while values below value suggest an ODI with an ipsilateral bias. CTL ND (black bar) have a characteristic and expected contralateral bias that significantly shifts to an ipsilateral bias after both 4dMD (CTL 4dMD, white hatched bar) and 7dMD (CTL 7dMD, white dotted bars). MMP9 KO ND (gray bar) displayed a contralateral bias, similar to CTL ND. Following 4dMD (gray hatched bar), MMP9 KO mice failed to demonstrate an ODP shift. ODP was apparent in MMP9 KO 7dMD (gray dotted bar). Statistics = Two-Way ANOVA with bonferroni multiple comparisons. All values reported are the mean ± SEM. *p < 0.05, **p < 0.001.
Mentions: Next we wanted to determine whether MMP9-mediated ECM degradation contributes to functional OD shifts. Therefore we performed intrinsic signal optical imaging (iOS) on control (C57Bl/6; CTL) and MMP9 KO mice following 4 days of monocular deprivation (4dMD) and quantified binocularity by calculating an ODI. An ODI above 0 represent a contralateral bias, while values below 0 represent an ipsilateral bias (Cang et al., 2005). CTL mice showed the expected contralateral bias in the absence of MD (Figures 5A,G, black bar, 0.163 ± 0.03). Following MD, responsiveness shifted from a contralateral to ipsilateral bias (Figures 5B,G, white hatched bar (−0.06 ± 0.06), white dotted bar (−0.07 ± 0.04). Non-deprived MMP9 KO mice also showed a strong contralateral response, with an ODI comparable to CTL ND mice (Figures 5D,G, gray bar, 0.212 ± 0.02). After 4 days of MD, however, ODIs failed to shift towards the ipsilateral eye (Figures 5E,G, gray hatched bar, 0.135 ± 0.04). To determine whether plasticity was reduced or slowed by the absence of MMP9, we repeated the experiment after 7 days of MD. By 7dMD, MMP9 KO mice displayed a significant ipsilateral shift similar to that observed in CTL 7dMD mice (Figures 5C,F,G, gray dotted bar, −0.02 ± 0.04, p < 0.05, two-way ANOVA, Bonferroni multiple comparisons) suggesting that MMP9 deficiency delays the induction or manifestation of ODP.

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