TDK conference 2017

Synaptic plasticity and activity-dependent morphological variability which underlie the function of neuronal networks in the mammalian brain have long been the focus of scientific interest. Particularly the organization of the synaptic actin-cytoskeleton, the dynamic scaffold of all neuronal contacts have recently been studied extensively since cytoskeletal dysfunctions are heavily implicated in psychiatric and neurodegenerative disorders. The synapses of the cerebellar parallel fibers (PF) and Purkinje cells (PC) play a key role in motor learning; interestingly structural and molecular abnormalities have been observed in these type of synaptic contacts in a number of neurodegenerative disorders. As very little is known about the molecular organization of the cytoskeleton in these PF-PC connections, we have studied the subcellular distribution of one of the main actin-regulatory proteins cortactin in the postsynaptic dendritic spines, the target of the excitatory PF input. This protein is responsible for the stabilization of actin filaments during plasticity. Previously-published evidence suggests that in the forebrain cortactin concentrates mainly in the core of dendritic spines, where it stabilizes actin-branchpoints. However, synaptic and structural plasticity and the molecular composition of the cerebellar PF-PC synapses significantly differs from that of the forebrain. Because of these known functional differences, we used immunocytochemistry and quantitative immunoelectron microscopy to elucidate the organization of cortactin in PC spines. Our data indicate, that cortactin is situated not only at the synapse and but also at the periphery of the spinoplasm (spine shell), closely associated with the non-synaptic plasma membrane. The present data from PC spines indicate, that – among others - the distribution of cortactin may underlie the unique cerebellar synaptic plasticity.