Progressive recovery of learning during regeneration of a single synapse in the medicinal leech

The leech escape reflex—shortening of the body—can change with nonassociative conditioning, including sensitization, habituation, and dishabituation. Capacity for sensitization, which is an enhancement of the reflex, is lost when a single S‐interneuron is ablated, but the reflex response itself remains. In the present experiments, the S‐interneuron's axon in the living leech was filled with 6‐carboxyfluorescein (6‐CF) dye and cut with an argon laser microbeam (λ = 488 nm). In contrast to sham‐operated animals, axotomized preparations did not sensitize, reflecting the key role of the S‐cell. By 2 weeks or more, S‐cell axons had regenerated and reestablished synapses at their usual locations with neighboring S‐cells. By 4 weeks, this restored the ability to sensitize to a level indistinguishable from that of controls, but an intermediate state of recovery was seen from 2–3 weeks after injury—a period not previously examined. The small capacity for sensitization among newly regenerated preparations was significantly lower than in sham controls but appeared higher than in animals whose cut S‐cell axon had not regenerated its synapse. The results confirm the crucial role of the S‐cell in sensitization. Moreover, full sensitization does not occur immediately upon synapse regeneration. J. Comp. Neurol. 457:67–74, 2003. © 2003 Wiley‐Liss, Inc.