Mechanisms underlying axonal plasticity and computational abilities

轴突可塑性和计算能力的机制

• 批准号: RGPIN-2020-05255
• 负责人: Kolta, Arlette
• 金额: $ 4.23万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716951
• 关键词: Mechanisms; underlying; axonal; plasticity; computational

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.

神经功能依赖于神经元的通信能力，而这种通信模式被认为依赖于神经元整合冲击其体细胞和树突过程的输入的能力，并在膜电位的变化使轴突初始段（AIS）达到阈值时通过其轴突乔木传递该信息。在AIS产生的动作电位（ap）被认为在轴突树中均匀传播，但越来越多的证据激起了对这些“教条”的修订。研究表明：1)AIS具有可塑性：神经元受到或过度刺激导致其长度、位置和离子通道组成发生变化。2)轴突并非“被动”传导AP：位于轴突干上的递质受体的激活可以改变AP的传播。3)通过控制离子胞外环境、髓磷脂的厚度和Ranvier结的大小，胶质细胞影响AP的传播速度（从而影响整体的同步性）。形成髓鞘的少突胶质细胞通过间隙连接与Ranvier节点上的星形胶质细胞相互作用，星形胶质细胞和少突胶质细胞偶联形成所谓的盘状网络。在此，我们建议利用电生理学、光遗传学、成像和免疫组织化学来研究胶质细胞和旁耳网络如何促进：1)AIS的可塑性，2)位于中脑三叉神经核（NVmes）的初级传入神经元轴突轴突的区隔化，以及3)APs传导速度的调节。