C02: The role of mechanics for neuronal ‘plasticity’

Activity-dependent structural rearrangements of the neuronal network are fundamental for correct wiring in juvenile brain. Upon their establishment, the neuronal network needs to be stabilised to guarantee circuit functional fidelity, which is achieved by the formation of a perineuronal extracellular matrix (ECM) during adolescence. The perineuronal ECM is a mesh-like structure with a backbone composed of hyaluronic acid and chondroitin sulphate proteoglycans, interacting with various secreted and membrane-associated molecules. This phase of brain development coincides with changes in mechanical properties of brain tissue, which may be due to the physical properties of the perineuronal ECM. Thus, ECM-derived changes in the mechanical properties of the brain tissue may contribute to network stabilisation and the decline in neuronal ‘plasticity’ observed in the adult brain. However, up to date this link has not been tested directly. To close this gap, C02 will analyse the effect of unilateral enzymatic ECM removal on the mechanical properties of the brain tissue using atomic force microscopy (AFM) indentation and Brillouin microscopy (BM). In the second step, we will culture neurons in artificial ECM with variable mechanic properties but similar composition to address the effect of varying viscoelasticity on synapse formation and activity-dependent structural ‘plasticity’ assessed by monitoring the dynamic formation and growths of dendritic spines. Finally, we will increase instantaneously and reversibly the density (hence, mechanical properties) of the endogenous ECM by optogenetic means and monitor effect of these manipulation on activity-dependent spine dynamics. Taken together, these results will provide valuable information about the contribution of the ECM to brain mechanics and the role of the viscoelastic properties of the ECM in neuronal ‘plasticity’.

Project leader: Dr. Renato Frischknecht

Positions: 1 doctoral researcher