Structural and functional restoration by collateral sprouting of hippocampal 5-HT axons

Abstract

DAMAGED 5-HT (5-hydroxytryptamine) axons in the central nervous system have been observed to undergo vigorous sprouting^1,2. Regeneration of these axons to their original termination sites has been seen several months after intraventricular administration of selective 5-HT neurotoxic drugs; and in the spinal cord this regrowth has been correlated with a return of normal 5-HT receptor function as measured by a hindlimb stretch reflex³. These findings raise two questions. First, is the pattern of re-innervation after injury dependent on some regenerative property of the damaged axons themselves, or is it primarily controlled by the denervated terminal field? And second, can re-innervation take place not only by regeneration of the original axons but also by collateral sprouting of chemically identical but anatomically separate undamaged fibres; and , if so, will function be restored? In the work reported here we have taken advantage of the fact that the hippocampus receives two separate inputs of 5-HT fibres from the median raphe nucleus, and we have shown that the unilateral removal of one input induces re-innervation of the unoccupied sites by the other. This collateral sprouting occuring in a single hippocampus is accompanied by disappearance of an asymmetrical behavioural response, suggesting that not only structural but functional recovery has occurred. Our results, therefore, suggest that the 5-HT terminal field plays a major part in the reorganisation of this system after injury to the brain.