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Review
. 2022 Mar 8;11(6):923.
doi: 10.3390/cells11060923.

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

Fernando Peña-Ortega  1 , Ángel Abdiel Robles-Gómez  1 , Lorena Xolalpa-Cueva  1
Affiliations
Review

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

Fernando Peña-Ortega et al. Cells. .

Abstract

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.

Keywords: excitability; memory; microtubules; protein Tau; synaptic plasticity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Microtubules (MTs) function in different neuronal compartments. In physiological conditions (A), MTs allow synaptic vesicles’ transport and recycling for proper synaptic transmission and plasticity. MTs contribute to the organization of the axon initial segment for action potential initiation and plasticity of intrinsic excitability. MTs are also capable of invading dendritic spines in an activity-dependent manner, for cargo delivery and postsynaptic plasticity regulation. However, when MTs dynamics and stability processes exceed the normal homeostatic range, under pathological conditions (B), there are MTs-dependent alterations in synaptic transmission due to inefficient synaptic vesicles’ transport, aberrant firing activity due to the relocation of the axon initial segment, loss of postsynaptic plasticity and alterations in dendritic spines due to reduced responsivity of MTs located in the dendritic shaft.
Figure 2
Figure 2
Differential effects caused by Paclitaxel. Paclitaxel is a microtubules stabilizer used in chemotherapy, which is capable of exerting both negative and positive effects on neural function and shape. (A) The most common negative effects associated with PTX are neuronal death, cognitive impairment, and sensory abnormalities (i.e., allodynia), that correlate with changes in brain activity and connectivity. (B) On the other hand, some positive effects of PTX are the enhancement of regeneration and elongation of axonal processes, restoration of axonal transport, and the reduction of glutamate-induced neurotoxicity.
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