Mechanical properties of perineuronal nets and their effect on synaptic plasticity

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This project aims to use atomic force microscopy (AFM) to probe the mechanical properties (stiffness, elasticity) of adult PNN-bearing neurons and to investigate if mechanical properties of the PNNs affect number of synapses contacting the PNN-neuron.PNNs are condensed extracellular matrix structures that encase neurons in the central nervous system (CNS). THey appear during natural development and terminate periods of juvenile plasticity in the CNS. How the PNNs cause this restriction of plasticity is still being investigated. One theory is that the PNNs act as a mechanical barrier to synaptic connections from other neurons thus reducing synaptic plasticity. Tenascin-R and link proteins are known to cross-link components of the PNNs and thus may confer rigidity to PNNs. We shall investigate if knocking out these proteins would effect the mechanical properties of the PNN. The results will allow us a better understanding of the basic biological process of synaptic plasticity within the CNS, and its modulation by the expression of cross-linking molecules. Understanding synaptic plasticity relates to understanding the molecular basis for learning and memory, and also diseases of aberrant plasticity i.e. addiction, post-traumatic stress disorder. This is an interdisciplinary project in which AFM methods will be developed to study the mechanobiology of neurons and the PNNs surrounding them, which has not previously been achieved.