Synapse Specification for Regenerated Motoneurons in Crayfish muscle

Abstract

Crustacean motoneurons fall into two broad classes of phasic and tonic, and within each class individual neurons show considerable differentiation of their synapses. Hence, regeneration of adult crustacean neuromuscular systems provides opportunities for assessing the role of the neuron and its target in specifying synapses. The crayfish abdominal superficial flexor muscle (SFM) is a particularly profitable preparation for examining the regeneration of tonic synapses. Here, a small population of tonic axons sprout from their cut proximal ends and reinnervate the linearly arranged glow muscle fibers, with differentiated synapses that resemble those formed by the original innervation. Manipulation of the nerve or of the target muscle revealed that some neurons regenerate synapses which are differentiated in a regional manner similar to the synapses of the intact axon, implying a retrograde signaling mechanism. Other regenerating neurons, however, deviate from their intact regional distribution, implying a cell autonomous mechanism for specification of synaptic properties. Selective operation of either presynaptic or postsynaptic influences may account for synapse specification of individual motoneurons. Conversely, regeneration and differentiation of phasic and tonic synapses appear to be intrinsically regulated, as demonstrated by allotransplanting a donor tonic or phasic nerve with its attendant ganglion onto a denervated host SFM. Compared to normal tonic synapses, regenerated phasic synapses show a greater initial release of transmitter, have thinner, mitochondria-sparse terminals, and exhibit synapses with more active zones. These properties are reminiscent of native phasic synapses. Thus, regeneration of phasic and tonic synapses appears to be regulated by the neuron itself, while synapse differentiation within each neuronal class appears to be regulated by the target muscle. Evidence for both regulatory mechanisms was found inDrosophilamotoneurons, which develop a fixed number of active zones in the absence of a target, suggesting an intrinsic mechanism, while their synaptic transmitter release is heavily modulated by a retrograde signaling mechanism. Such combinatorial effects in synapse specification may permit an optimal match between neuron and target.

Acknowledgements. I am indebted to Sam Velez for pioneering studies of crayfish neuromuscular regeneration, Kristin Krause for allotranplanting foreign nerves and Joanne Pearce, Rosalind Coulthard, and Rahim Hirji for defining the fine structure of regenerated synapses. Research support was provided by the Natural Sciences and Engineering Research Council of Canada.