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Repair and Regeneration of Functional Synaptic Connections: Cellular and Molecular Interactions in the Leech

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Abstract

A major problem for neuroscience has been to find a means to achieve reliable regeneration of synaptic connections following injury to the adult CNS. This problem has been solved by the leech, where identified neurons reconnect precisely with their usual targets following axotomy, re-establishing in the adult the connections formed during embryonic development.

It cannot be assumed that once axons regenerate specific synapses, function will be restored. Recent work on the leech has shown following regeneration of the synapse between S-interneurons, which are required for sensitization of reflexive shortening, a form of non-associative learning, the capacity for sensitization is delayed.

The steps in repair of synaptic connections in the leech are reviewed, with the aim of understanding general mechanisms that promote successful repair. New results are presented regarding the signals that regulate microglial migration to lesions, a first step in the repair process. In particular, microglia up to 900 μm from the lesion respond within minutes by moving rapidly toward the injury, controlled in part by nitric oxide (NO), which is generated immediately at the lesion and acts via a soluble guanylate cyclase (sGC). The cGMP produced remains elevated for hours after injury. The relationship of microglial migration to axon outgrowth is discussed.

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Authors and Affiliations

  1. Department of Physiology & Biophysics, University of Miami School of Medicine, Miami, Florida, 33136

    Yuanli Duan, Joseph Panoff & Kenneth J. Muller

  2. Neuroscience Group, Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, South Dakota, 57069

    Brian D. Burrell

  3. Department of Biological Sciences, Purdue University, West Lafayette, Indiana, 47907

    Christie L. Sahley

  4. Neuroscience Program, University of Miami School of Medicine, Miami, Florida, 33136

    Kenneth J. Muller

  5. RMSB 5089, Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10 Avenue, Miami, Florida, 33136

    Kenneth J. Muller

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  1. Yuanli Duan
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  2. Joseph Panoff
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  4. Christie L. Sahley
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  5. Kenneth J. Muller
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Correspondence to Kenneth J. Muller.

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Duan, Y., Panoff, J., Burrell, B.D. et al. Repair and Regeneration of Functional Synaptic Connections: Cellular and Molecular Interactions in the Leech. Cell Mol Neurobiol 25, 441–450 (2005). https://doi.org/10.1007/s10571-005-3152-x

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