Microtubules as Regulators of Neural Network Shape and Function: Focus on Excitability, Plasticity and Memory

Neuronal microtubules (MTs) are complex cytoskeletal protein arrays that undergo activity-dependent changes in their structure and function as a response to physiological demands throughout the lifespan of neurons. Many factors shape the allostatic dynamics of MTs and tubulin dimers in the cytosolic microenvironment, such as protein-protein interactions and activity-dependent shifts in these interactions that are responsible for their plastic capabilities. Recently, several findings have reinforced the role of MTs in behavioral and cognitive processes in normal and pathological conditions. In this review, we summarize the bidirectional relationships between MTs dynamics, neuronal processes, and brain and behavioral states. The outcomes of manipulating the dynamicity of MTs by genetic or pharmacological approaches on neuronal morphology, intrinsic and synaptic excitability, the state of the network, and behaviors are heterogeneous. We discuss the critical position of MTs as responders and adaptative elements of basic neuronal function whose impact on brain function is not fully understood, and we highlight the dilemma of artificially modulating MT dynamics for therapeutic purposes.