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Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood.

Levy AD, Omar MH, Koleske AJ - Front Neuroanat (2014)

Bottom Line: The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity.While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands.Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Neuroscience Program, Yale University New Haven, CT, USA ; Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA.

ABSTRACT
Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer's disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

No MeSH data available.


Related in: MedlinePlus

Chondroitin sulfate proteoglycans around spines restrict spine dynamics and functional plasticity. (A) In juvenile animals during the critical period, CSPG expression is low and visual monocular deprivation (MD) can increase spine motility in primary visual cortex and drive changes in ocular dominance (OD) plasticity. (B) In adult animals after the critical period, CSPG expression is high and MD can no longer increase spine motility or drive OD plasticity. However, treatment with chondroitinaseABC (chABC) to degrade CSPG glycosaminoglycan (GAG) chains allows MD to once again increase spine motility and drive OD plasticity in adults, demonstrating that CSPGs restrict spine remodeling and functional plasticity in adult animals.
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Figure 3: Chondroitin sulfate proteoglycans around spines restrict spine dynamics and functional plasticity. (A) In juvenile animals during the critical period, CSPG expression is low and visual monocular deprivation (MD) can increase spine motility in primary visual cortex and drive changes in ocular dominance (OD) plasticity. (B) In adult animals after the critical period, CSPG expression is high and MD can no longer increase spine motility or drive OD plasticity. However, treatment with chondroitinaseABC (chABC) to degrade CSPG glycosaminoglycan (GAG) chains allows MD to once again increase spine motility and drive OD plasticity in adults, demonstrating that CSPGs restrict spine remodeling and functional plasticity in adult animals.

Mentions: Chondroitin sulfate proteoglycans normally stabilize dendritic spines. The physiological changes induced by MD are associated with a reduction in spine density of layer II/III visual cortical neurons responsive to the deprived eye (Mataga et al., 2004; Pizzorusso et al., 2006). This loss of spines can be rescued by opening the deprived eye and closing the previously open eye, but only in juvenile animals. However, chABC treatment reinstates this plasticity in adult animals, demonstrating that CSPGs normally stabilize existing spines (Pizzorusso et al., 2006). Loss of CSPGs also enhances spine motility, measured as the magnitude of fluctuations in spine length over time (Figure 1C). Spine motility decreases with age (Majewska and Sur, 2003), but chABC treatment of adult visual cortex in vivo and of hippocampal organotypic slices in vitro enhances spine motility (Orlando et al., 2012; de Vivo et al., 2013), reverting spines to a more immature phenotype. This is similar to the effect of MD, which also increases spine motility (Oray et al., 2004). These results demonstrate that CSPGs stabilize dendritic spine structure and movement (Figures 3A,B).


Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood.

Levy AD, Omar MH, Koleske AJ - Front Neuroanat (2014)

Chondroitin sulfate proteoglycans around spines restrict spine dynamics and functional plasticity. (A) In juvenile animals during the critical period, CSPG expression is low and visual monocular deprivation (MD) can increase spine motility in primary visual cortex and drive changes in ocular dominance (OD) plasticity. (B) In adult animals after the critical period, CSPG expression is high and MD can no longer increase spine motility or drive OD plasticity. However, treatment with chondroitinaseABC (chABC) to degrade CSPG glycosaminoglycan (GAG) chains allows MD to once again increase spine motility and drive OD plasticity in adults, demonstrating that CSPGs restrict spine remodeling and functional plasticity in adult animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202714&req=5

Figure 3: Chondroitin sulfate proteoglycans around spines restrict spine dynamics and functional plasticity. (A) In juvenile animals during the critical period, CSPG expression is low and visual monocular deprivation (MD) can increase spine motility in primary visual cortex and drive changes in ocular dominance (OD) plasticity. (B) In adult animals after the critical period, CSPG expression is high and MD can no longer increase spine motility or drive OD plasticity. However, treatment with chondroitinaseABC (chABC) to degrade CSPG glycosaminoglycan (GAG) chains allows MD to once again increase spine motility and drive OD plasticity in adults, demonstrating that CSPGs restrict spine remodeling and functional plasticity in adult animals.
Mentions: Chondroitin sulfate proteoglycans normally stabilize dendritic spines. The physiological changes induced by MD are associated with a reduction in spine density of layer II/III visual cortical neurons responsive to the deprived eye (Mataga et al., 2004; Pizzorusso et al., 2006). This loss of spines can be rescued by opening the deprived eye and closing the previously open eye, but only in juvenile animals. However, chABC treatment reinstates this plasticity in adult animals, demonstrating that CSPGs normally stabilize existing spines (Pizzorusso et al., 2006). Loss of CSPGs also enhances spine motility, measured as the magnitude of fluctuations in spine length over time (Figure 1C). Spine motility decreases with age (Majewska and Sur, 2003), but chABC treatment of adult visual cortex in vivo and of hippocampal organotypic slices in vitro enhances spine motility (Orlando et al., 2012; de Vivo et al., 2013), reverting spines to a more immature phenotype. This is similar to the effect of MD, which also increases spine motility (Oray et al., 2004). These results demonstrate that CSPGs stabilize dendritic spine structure and movement (Figures 3A,B).

Bottom Line: The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity.While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands.Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

View Article: PubMed Central - PubMed

Affiliation: Interdepartmental Neuroscience Program, Yale University New Haven, CT, USA ; Department of Molecular Biophysics and Biochemistry, Yale University New Haven, CT, USA.

ABSTRACT
Dendritic spines are the receptive contacts at most excitatory synapses in the central nervous system. Spines are dynamic in the developing brain, changing shape as they mature as well as appearing and disappearing as they make and break connections. Spines become much more stable in adulthood, and spine structure must be actively maintained to support established circuit function. At the same time, adult spines must retain some plasticity so their structure can be modified by activity and experience. As such, the regulation of spine stability and remodeling in the adult animal is critical for normal function, and disruption of these processes is associated with a variety of late onset diseases including schizophrenia and Alzheimer's disease. The extracellular matrix (ECM), composed of a meshwork of proteins and proteoglycans, is a critical regulator of spine and synapse stability and plasticity. While the role of ECM receptors in spine regulation has been extensively studied, considerably less research has focused directly on the role of specific ECM ligands. Here, we review the evidence for a role of several brain ECM ligands and remodeling proteases in the regulation of dendritic spine and synapse formation, plasticity, and stability in adults.

No MeSH data available.


Related in: MedlinePlus