Mechanisms underlying axonal plasticity and computational abilities

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Nervous functions rely on the ability of neurons to communicate, and this communication mode is thought to rely on the capacity of neurons to integrate inputs impinging on their soma and dendritic processes and to transmit this information through their axonal arbors if the changes in membrane potential bring the axon initial segment (AIS) to threshold. Action potentials (APs) generated at the AIS are thought to propagate uniformly across the axonal tree, but growing evidence incite revisions of these "dogmas". Studies have shown that: 1) AIS are plastic: Under or over stimulation of neurons lead to changes in their length, position and ion channel composition. 2) Axons are not "passively" conducting APs: Activation of transmitter receptors located on the axonal trunk can alter AP propagation, and 3) By controlling the ionic extracellular environment, the thickness of the myelin and the size of Ranvier nodes, glial cells affect AP speed of propagation (with consequences on synchrony in an ensemble). Oligodendrocytes forming the myelin interact with (perinodal) astrocytes at Ranvier nodes through gap junctions and coupled astrocytes and oligodendrocytes form what are called panglial networks. Here we propose to use electrophysiology, optogenetic, imaging and immunohistochemistry to examine how glial cells and panglial networks contribute to: 1) plasticity of the AIS and 2) Compartmentalization of the axonal arbor of primary afferent neurons located in the mesenscephalic trigeminal nucleus (NVmes), and 3) Regulation of conduction velocity of APs. NVmes represent a unique opportunity to address these questions because of their large axons that can be maintained and easily targeted for recording in brainstem slices. In Aim 1) we will examine how short term increase of their activity affects the length and position of their AIS using a method to vary focally the extracellular Ca2+ concentration or using Na+ indicators. Live measurements will be confirmed with post-hoc immuno-histochemical labelling with antibodies against Ankyrin G or BetaIV spectrin. AIS changes obtained with these methods will be compared before and after activation or inactivation of astrocytes and/or their coupling with oligodendrocytes. Aims 2 and 3) will examine how astrocytes/oligodendrocytes interactions can affect propagation and conduction velocity of APs in a branch specific manner. There is evidence of GABA dependent decoupling between different compartments of NVmes axons. Here we will examine the effect of astrocytes and/or oligodendrocytes manipulations on propagation of orthodromic and antidromic APs in different axonal branches of NVmes cells and will try to identify the gliotransmitter underlying any observed effect. These experiments raise novel and original questions that may have wide implications on our understanding of factors determining the most basic neuronal functions of computation and communication.