Functional repair of motor endplates after botulinum neurotoxin type A poisoning: Biphasic switch of synaptic activity between nerve sprouts and their parent terminals

Blockade of acetylcholine release by botulinum neurotoxin type A at the neu romuscular junction induces the formation of an extensive network of nerve- terminal sprouts. By repeated in I ilo imaging of N-(3-triethyl ammonium pr opyl)-4-(4-(dibutylamino)styryl) pyridinium dibromide uptake into identifie d nerve endings of the mouse sternomastoid muscle after a single intramuscu lar injection of the toxin, inhibition of stimulated uptake of the dye at t he terminals was detected within a few days, together with an increase in s taining of the newly formed sprouts. After 28 days, when nerve stimulation again elicited muscle contraction, regulated vesicle recycling occurred onl y; in the sprouts [shown to contain certain soluble N-ethylmaleimide-sensit ive factor attachment proteins (SNAREs) and to abut acetylholine receptors] and not at the parent terminals. Therefore. only these sprouts could be re sponsible for nerve-muscle transmission at this time. However, a second, di stinct phase of the rehabilitation process followed with a return of vesicl e turnover to the original terminals, accompanied by an elimination of the by then superfluous sprouts. This extension and later removal of "functiona l"? sprouts indicate their fundamental importance in the repair of paralyze d endplates, a finding,vith ramifications for the vital process of nerve re generation.