BMI SEMINAR // Extracellular matrix and neuroplasticity in health and disease

Neural extracellular matrix (ECM) molecules derived from neurons and glial cells accumulate in the extracellular space and regulate synaptic plasticity through modulation of perisomatic GABAergic inhibition, intrinsic dendritic and axonal excitability, lateral diffusion of synaptic molecules, integrin signaling, as well as activities of L-type Ca2+ channels, NMDA receptors, and small GTPases (Dityatev et al., Nat Rev Neurosci, 2010). Genetic or enzymatic targeting of ECM molecules proved to bi-directionally modulate synaptic plasticity and acquisition/recall of memories, depending on experimental conditions, and to promote cognitive flexibility and extinction of fear and drug memories (Senkov et al., Progr Brain Res, 2014). Upregulation of ECM expression is associated with aging and dementia, while epileptic seizures and schizophrenia may result in attenuation of ECM. Thus, the neural ECM appeared as a key component of synaptic plasticity, learning and memory, and may be linked to cognitive dysfunctions in major brain disorders.