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Synaptic elimination and protection after minimal injury depend on cell type and their prelesion structural dynamics in the adult cerebral cortex

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posted on 2023-05-17, 20:06 authored by Alison CantyAlison Canty, Teles-Grilo Ruivo, LM, Nesarajah, C, Song, S, Jackson, JS, Little, GE, De Paola, V
The axonal and synaptic mechanisms underlying dysfunction and repair of the injured CNS are poorly understood. Unresolved issues include to what degree, when, and how the surviving neurons degenerate and the extent of synaptic remodeling both along the severed axon and in the nearby area. One of the main reasons is the lack of tools to study the complex asynchronous and dynamic features of individual lesioned axon responses in the intact brain. To address these issues, we combined two-photon microscopy and laser microsurgery to image the real-time reorganization of cortical circuitry at synaptic resolution for periods of up to 1 year in the brain of living mice. Injured cortical axons were eliminated proximally through a two-phase retraction process, which continued for at least 3 months postlesion and was independent of the presence of scar tissue. Remarkably, axons which later attempt to regenerate in both the mature and juvenile brain retracted less, raising the possibility that targeting retraction may improve the chances of axon regrowth after axotomy. Comparing prelesion and postlesion dynamics on the same axons over several days and weeks revealed that, although synapse formation rates were unaffected, boutons on injured axons were either rapidly and persistently lost, or extremely resistant, depending on cell-type and their prelesion structural dynamics. Our data suggest a lasting deficiency in synaptic output on surviving injured cortical axons and a surprising difference in the vulnerability of synaptic boutons after axotomy, which depend on cell-type and their recent history.

History

Publication title

Journal of Neuroscience

Volume

33

Issue

25

Pagination

10374-83

ISSN

0270-6474

Department/School

Tasmanian School of Medicine

Publisher

Soc Neuroscience

Place of publication

11 Dupont Circle, Nw, Ste 500, Washington, USA, Dc, 20036

Rights statement

Copyright 2013 the authors

Repository Status

  • Open

Socio-economic Objectives

Clinical health not elsewhere classified

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