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

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.

Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning

“…After CSPG degradation with ChABC in adult rats, monocular deprivation caused an ocular dominance shift toward the non-deprived eye. Therefore the mature ECM of the adult visual cortex blocks experience-dependent plasticity, and removal of CSPGs reactivates plasticity (Levy et al, 2014; Pizzorusso et al, 2002). Furthermore, during early postnatal development, fear memories are easily erased via extinction paradigms as compared to adulthood (Kim and Richardson, 2007).…”

“…The neural extracellular matrix (ECM) surrounding cells, synapses and processes in the central nervous system, could be one such player in the maintenance of synaptic morphology and memory traces through complex interactions between neurons and molecules (Levy et al, 2014). The ECM is thought to play particularly important roles in spine and synapse stability and plasticity as it provides a scaffold in the extracellular space (Celio and Blumcke, 1994) in addition to regulating neural plasticity through associations with signaling molecules in development and adulthood (Dyck and Karimi-Abdolrezaee, 2015; Sherman and Back, 2008).…”

“…The ECM is thought to play particularly important roles in spine and synapse stability and plasticity as it provides a scaffold in the extracellular space (Celio and Blumcke, 1994) in addition to regulating neural plasticity through associations with signaling molecules in development and adulthood (Dyck and Karimi-Abdolrezaee, 2015; Sherman and Back, 2008). The ECM is composed of a meshwork of interconnected proteins and carbohydrates (Levy et al, 2014) including chondroitin sulphate proteoglycans (CSPGs) of the lectican family. Lecticans such as aggrecan, brevican and neurocan are widely implicated in the organization, development, normal maintenance and pathology of the CNS (Avram et al, 2014; Bandtlow and Zimmermann, 2000).…”

Signals from the Fourth Dimension Regulate Drug Relapse

“…Neuropil ECM is ubiquitous in the extracellular space, and like PNNs, contains collagen, laminin, and fibronectin and associates with pre- and post-synaptic CAMs [90]. Through interactions with CAMs, perisynaptic ECM proteins function in mature brains to stabilize dendritic spine structure, and can be restructured through catabolism to regulate glutamatergic transmission and synaptic plasticity [13]. ECM degradation is accomplished largely by constitutive and inducible activity of MMPs (Box 2) [90].…”

Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer

“…Synapse organization involves physical attachment, and it is not surprising that an adhesion molecule such as RS1 would play a role in stabilizing a functional synapse and also in modulating experience-driven plasticity. Several synaptic celladhesion molecules and ECM components around the synaptic cleft facilitate the organization, alignment, and maturation of synaptic networks, and they are often referred to as synapse adhesion molecules (52)(53)(54)(55). Many are members of the cadherin, integrin, and immunoglobulin super-families.…”