Synaptic connections within the adult brain are not fixed and stable but remarkably flexible. This reorganisation of synaptic connectivity is a basic principle of neuronal plasticity and believed to represent the cellular basis for learning and memory function. Dendritic spines form the dynamic postsynaptic component of most excitatory synapses in the brain. Recent studies from the host laboratory revealed the invasion of microtubules (MT) into dendritic spines. Several lines of evidence indicate that synaptic activation increases MT entry in spines. However, it remains unclear how synaptic signals trigger intraspinal MTs and what is the effect of MT invasion for spine structure and function.The proposed project is aimed to investigate the functional consequences of dynamic microtubules in spine plasticity. We will combine molecular biology, organotypic slice cultures, quantitative/high resolution microscopy, and electrophysiology to investigate the role of MT based mechanisms in synaptic plasticity. In this application we propose to: Objective 1. Characterise synaptic signals that control MT spine entry. We will analysis different neuronal activation patterns as potential triggers of MT spine invasions. Objective 2. Determine the role of MT spine entry for structural spine plasticity. Functionally, dynamic MTs can contribute to dendritic spine plasticity by regulating intraspinal actin dynamics or cargo transport into spines. We will test whether MT entry stabilize/modify the invaded spine in slice cultures and analyse the role of dynamic MT in the development of immature dendritic protrusions. Objective 3. Examine the role of dynamic MT for cargo trafficking into spines. The role of dynamic MT for transport of cargo into spines will be studied by analysing kinesin/dynein motor dynamics during spine invasion of MTs. The results of this project will contribute to the fundamental understanding of spine and synapse plasticity.