Abstract
AbstractSuccessful neuronal regeneration requires the re-establishment of synaptic connectivity. Crucial to this process is the reconstitution of presynaptic machinery responsible for controlling neurotransmitter release. In the mammalian adult CNS post-injury regeneration is usually only possible after extensive experimental intervention, and it is unknown how presynaptic function is re-established, let alone how it might be optimised to promote functional recovery. Here we addressed these questions by studying presynaptic maturation during a regenerative process that occurs entirely naturally. After toxin-induced injury, olfactory sensory neurons in the adult mouse olfactory epithelium can regenerate fully, sending axons to the brain to re-establish synaptic contact with postsynaptic partners in the olfactory bulb. Using electrophysiological recordings in acute slices, we found that after initial re-contact, functional connectivity in this system was rapidly established. Moreover, re-connecting presynaptic terminals had almost mature functional properties, including high release probability and a strong capacity for presynaptic inhibition. Release probability then matured quickly, rendering re-established terminals functionally indistinguishable from controls just one week after initial contact. These data show that successful synaptic regeneration in the adult mammalian brain is not quite a ‘plug-and-play’ process; instead, almost-mature presynaptic terminals undergo a rapid phase of functional maturation to re-integrate into established target networks.
Publisher
Cold Spring Harbor Laboratory