Repair and regeneration of functional synaptic connections: Cellular and molecular interactions in the leech

Yuanli Duan, Joseph Panoff, Brian D. Burrell, Christie L. Sahley, Kenneth J. Muller

Research output: Contribution to journalReview article

24 Scopus citations

Abstract

1. 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. 2. 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. 3. 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.

Original languageEnglish (US)
Pages (from-to)441-450
Number of pages10
JournalCellular and molecular neurobiology
Volume25
Issue number2
DOIs
StatePublished - Apr 2005

Keywords

  • Cell migration
  • Microglia
  • Nerve regeneration
  • Neuronal plasticity
  • Nitric oxide
  • Non-associative learning
  • Sensitization
  • Time-lapse video

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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