In contrast to adult mammals, axons of goldfish central neurons are capable of regenerating across spinal cord lesions and establishing neuronal circuits that support behavioral recovery. Our long-term goal is to determine mechanisms underlying both the successful regeneration and recovery of function by identified goldfish CNS neurons, in order to develop strategies that will maximize conditions favoring functional recovery from spinal injury in mammals.. For this purpose we use the goldfish Mauthner (M-) cell, an identifiable reticulospinal neuron that mediates a defined behavior, the C-start, and whose inputs and outputs are precisely known. A few months after spinal cord injury, the M-axon regenerates across the lesion, stimulation of the regenerated axon can produce trunk electromyographic responses, and the C-start behavior returns. The experiments proposed here are designed to elucidate the role of the M-axon and its output connections in this behavioral recovery, and to determine if the new connectivity mimic that established normally or whether alternative strategies are adopted.
Specific Aim 1 uses behavioral, morphological and electrophysiological measurements to test the hypothesis that the M-cell contributes to the recovery of the C-start behavior following a spinal cord crush.
In Specific Aim 2, intracellular recordings will be used as well, to determine if the regenerating M-axon reestablishes functional synapses with motoneurons and/or descending spinal interneurons that synapse with motoneurons. Similarly, in Aim 3 we will correlate the changes in the C-start and in the functional properties of identified supraspinal output synapses of the M-axon with the process of axonal regeneration. Finally, in Aim 4 we will test the hypothesis that nonneuronal cells support regeneration of the M-axon by providing an environment conductive to growth. The results of these studies will provide important insight concerning the clinical problem of the recovery of locomotor function following spinal cord injury.
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