Impaired axon regeneration and heightened synaptic dynamics in the injured aged mammalian cortex

Abstract

How aging affects axon regeneration and synaptic repair in the brain is poorly understood. To study age-related changes in neural circuits, we developed a model of axonal injury in the aged (> 2 years) mouse somatosensory cortex. By directly tracking fluorescently labelled injured axons by multiphoton imaging, we find that while axon degeneration in the aged brain is comparable to the young adult brain, axon regeneration is impaired. We further examine changes in the most common type of cortical synapses, En Passant Boutons (EPBs), and observe a transient and significant increase in the number and size of boutons 6 hours post-lesion. Using a computational model of a recurrent neural network, we examined the functional consequences of these synaptic increases on memory, comparing results to models of the young adult brain. The results suggest that increased synaptic dynamics might enable partial recovery from injury via synaptic re-wiring in the aged brain. HighlightsO_LIImpaired axon regeneration in the aged brain is not due to slowed degeneration. C_LIO_LISynaptic reorganization occurs following axon injury in the aged brain. C_LIO_LISynaptic reorganization may serve as a compensatory mechanism after injury. C_LI