Novel Synapses Compensate for a Neuron Ablated in Embryos

In leeches, as well as mammals, neuronal death in adults produces lasting deficits, whereas the embryonic nervous system is believed to be more plastic. Killing the single S interneuron in an adult leech ganglion permanently interrupts the chain of S cells linked by electrical synapses along the entire animal. Axons that synapsed with the ablated neuron do not change length in response to cell ablation, but they will grow if another axon of the same neuron is injured. In the present experiments, the S cell and surrounding cells in one ganglion were ablated with a fine pin during embryogenesis (day 8-11). Effects were evaluated 1-4 months later. Cell-specific monoclonal antibody confirmed S cell deletions. Intracellular injection of horseradish peroxidase and 6-carboxyfluorescein dye showed that intact S cells' axons projected twice their usual length into the lesioned ganglion and formed electrical synapses with homologues of their usual synaptic targets. Conduction was often restored by these connections, which replaced those of the deleted S cell. Therefore, in both adults and embryos, growing S interneurons respond to loss of a target by greater growth. However, only on the small scale of the embryo is growth sufficient to reach suitable targets. In leeches, as well as mammals, neuronal death in adults produces lasting deficits, whereas the embryonic nervous system is believed to be more plastic. Killing the single S interneuron in an adult leech ganglion permanently interrupts the chain of S cells linked by electrical synapses along the entire animal. Axons that synapsed with the ablated neuron do not change length in response to cell ablation, but they will grow if another axon of the same neuron is injured. In the present experiments, the S cell and surrounding cells in one ganglion were ablated with a fine pin during embryogenesis (day 8-11). Effects were evaluated 1-4 months later. Cell-specific monoclonal antibody confirmed S cell deletions. Intracellular injection of horseradish peroxidase and 6-carboxyfluorescein dye showed that intact S cells' axons projected twice their usual length into the lesioned ganglion and formed electrical synapses with homologues of their usual synaptic targets. Conduction was often restored by these connections, which replaced those of the deleted S cell. Therefore, in both adults and embryos, growing S interneurons respond to loss of a target by greater growth. However, only on the small scale of the embryo is growth sufficient to reach suitable targets

Regeneration of a Central Synapse Restores Nonassociative Learning

Sensitization is a form of nonassociative learning in which a strong or noxious stimulus persistently enhances the response produced by a weaker stimulus. In the leech Hirudo medicinalis , the S-interneuron is required for sensitization of the shortening response. A single S-cell axon was surgically separated from its sole synaptic partner, the neighboring S-cell. This consistently eliminated sensitization without impairing reflexive shortening itself, as measured in semi-intact specimens. Sensitization of the shortening reflex returned after 3 weeks when the severed axon grew and regenerated its specific electrical synapse within the nerve cord, as shown by restored conduction of impulses between S-cells. This confirms the essential role of one neuron, the S-cell, in sensitization, and it demonstrates that regeneration of the synapse between S-cells restores this example of nonassociative learning

Atypical embryonic synapses fail to regenerate in adulthood

Functional recovery following central nervous system (CNS) injury in adult animals may depend on the reestablishment of the precise pattern of connections made during development. When the nervous system is injured during embryonic development, functional recovery may involve the formation of atypical connections. Can such atypical synapses regenerate in adults, particularly in a nervous system known for its capacity for repair? When the S interneuron in one segmental ganglion of the leech Hirudo is killed during development, two neighboring S cells extend their axons into the ganglion and restore function by making electrical synapses with the usual synaptic targets of the killed S cell. Although adult S-cell axons reliably regenerated their usual synaptic connections, the novel synapses induced following embryonic injury failed to regenerate in adults. In these preparations severed S-cell axons did not reach the denervated ganglion but grew close to it, independent of the distance required to grow. Thus, the developmental changes that permit aberrant but functional connections in embryos do not lead to a similar change in the capacity for axon growth and subsequent synapse regeneration in adults