Neuronal injuries induce profound changes in axons, dendrites, and synapses that usually lead to a devastating loss of function. While a large amount of research has broadened our understanding of axonal regeneration, very little is known about the ability of dendrites to regenerate after injury or deafferentation. Obviously, any successful clinical strategy will eventually need to consider the regeneration of dendrites and synapses if the full complexity of neuronal circuitry is to be restored. Crickets possess unusually robust responses to neuronal injury. Deafferented cricket auditory neuron dendrites grow across the boundary of the midline and form functional synaptic connections with the auditory afferents from the opposite ear. However, injury to the cercal escape system shows an entirely different type of recovery, consisting of physiological instead of structural reorganization. The long-term goal of our research is to understand the molecular control of dendritic growth and plasticity. The objective of this proposal is to identify key differences that underlie the distinctive responses of deafferented dendrites in the prothoracic and terminal ganglia. The aims of this project are: 1) Do identified protein candidates display predictable expression differences between the prothoracic and terminal ganglia that correlate with differential responses to injury?; 2) What similarities and differences exist between deafferented prothoracic AN neurons and deafferented terminal MGI neurons at the transcriptional level?; and 3) Are identified protein candidates necessary for the compensatory responses in these ganglia? Custom antibodies and RNAseq will be utilized in the first two aims. For the third aim, identified candidates will be manipulated using dsRNA and we will assess the behavioral, physiological and anatomical recovery. The research proposed in this application is significant because it will begin to identify components of two different mechanisms that both lead to successful responses to injury within one organism. An investigation of these invertebrate regeneration phenomena will advance our fundamental understanding of the plasticity of dendrites, and reveal principles governing dendritic responses to input loss that may be applicable to all neuronal systems, including mammals. mammalemammals.
Relevance of Research
Spinal cord injuries are devestating to humans because injured nerve cells can’t grow and reconnect. The simple nervous system of the cricket, on the other hand, recovers from injury remarkably well by compensating for sensory loss. It is our hope that exploring the strategies used in the injured cricket nervous system will give us tools that will be applicable to human spinal cord injuries.