Catecholaminergic axons in the neocortex of adult mice regrow following brain injury

Serotonin axons in the adult rodent brain can regrow and recover their function following several forms of injury including controlled cortical impact (CCI), a neocortical stab wound, or systemic amphetamine toxicity. To assess whether this capacity for regrowth is unique to serotonergic fibers, we used CCI and stab injury models to assess whether fibers from other neuromodulatory systems can also regrow following injury. Using tyrosine-hydoxylase (TH) immunohistochemistry we measured the density of catecholaminergic axons before and at various time points after injury. One week after CCI injury we observed a pronounced loss, across cortical layers, of TH+ axons posterior to the site of injury. One month after CCI injury the same was true of TH+ axons both anterior and posterior to the site of injury. This loss was followed by significant recovery of TH+ fiber density across cortical layers, both anterior and posterior to the site of injury, measured three months after injury. TH+ axon loss and recovery over weeks to months was also observed throughout cortical layers using the stab injury model. Double label immunohistochemistry revealed that nearly all TH+ axons in neocortical layer 1/2 are also dopamine-beta-hyroxylase+ (DBH+; presumed norepinephrine), while TH+ axons in layer 5 are a mixture of DBH+ and dopamine transporter+ types. This suggests that noradrenergic axons can regrow following CCI or stab injury in the adult mouse neocortex and leaves open the question of whether dopaminergic axons can do the same. Highlights We measured catecholaminergic axon density using tyrosine hydroxylase immunohistochemistry following two forms of brain injury. Both controlled cortical impact and cortical stab injuries caused extensive damage to catecholaminergic axons in the neocortex of adult mice. Following both types of injury, axon density slowly returned to control values over many weeks, including, in the case of stab injury, regrowth across the stab rift. Together with previous results showing serotonin axon regrowth, these findings suggest that monaminergic axons have an unusual capacity for regrowth following injury in the adult mammalian brain