Recovery of the electric organ discharge after spinal cord transection in the weakly electric fish Apteronotus leptorhynchus.

摘要

Spinal cord injury in adult mammals can result in irreversible impairment or abolishment of motor function. Unlike mammals, lower vertebrates regenerate spinal cord tissue in damaged areas and gradually recovery behavioral function. The electromotor system, a bulbospinal circuit that controls the electric organ discharge (EOD) in weakly electric fish is ideally suited for studying anatomical and functional recovery after spinal cord injury for several reasons: (1) the neural circuit is simple, (2) the EOD provides a clear, noninvasive index of physiological and functional recovery, and (3) the continuous EOD has been extensively characterized in normal animals. Regeneration of spinal cord following tail amputation has been well studied in the electric fish, Apteronotus leptorhynchus. Structural and functional recovery is achieved through proliferation of endogenous precursor cells and differentiation of their progeny. This dissertation focuses on quantifying cellular proliferation and recovery of the EOD after complete spinal transection rather than amputation. Using bromodeoxyuridine (BrdU), I quantified proliferating cell number throughout the spinal cord following injury. Spinal transection significantly increased proliferation and/or survival as indicated by an elevated density of BrdU cells along the entire length of the spinal cords of spinally transected compared to sham and un-operated fish. In the second experiment, I examined recovery of locomotion and the EOD. I used two different procedures: local EOD recordings measured the output of each rostro-caudal segment of the electric organ and global EOD recordings measured the coherent output of the entire electric organ. Locomotion was restored between 35-45 days post-transection (dpt). The power of the local discharge gradually increased before reaching a plateau at 180 dpt. The results of these experiments suggest that A. leptorhynchus can reestablish functional locomotor and electromotor circuits following spinal cord transection. These findings indicate that spinal cord injury stimulates widespread cellular proliferation along the entire length of the apteronotid spinal cord. It is likely that the BrdU-labeled cells found 30 days after the injury participate in spinal cord repair and functional recovery.