TY - JOUR
T1 - Repair and regeneration of functional synaptic connections
T2 - Cellular and molecular interactions in the leech
AU - Duan, Yuanli
AU - Panoff, Joseph
AU - Burrell, Brian D.
AU - Sahley, Christie L.
AU - Muller, Kenneth J.
N1 - Funding Information:
Supported in part by grants from NIH NINDS to CLS and KJM. JP supported by an NIH Training Grant and BDB by an NSF Grant. We thank Ms. Georgina Cruz, Dr. Brenda Moss, Dr. Emmanuel Ngu, Ms. Bertina Scott and Dr. Alec Urazaev for helpful discussions.
PY - 2005/4
Y1 - 2005/4
N2 - 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.
AB - 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.
KW - Cell migration
KW - Microglia
KW - Nerve regeneration
KW - Neuronal plasticity
KW - Nitric oxide
KW - Non-associative learning
KW - Sensitization
KW - Time-lapse video
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U2 - 10.1007/s10571-005-3152-x
DO - 10.1007/s10571-005-3152-x
M3 - Review article
C2 - 16047551
AN - SCOPUS:20044379233
SN - 0272-4340
VL - 25
SP - 441
EP - 450
JO - Cellular and molecular neurobiology
JF - Cellular and molecular neurobiology
IS - 2
ER -