Refinement of an Inhibitory Interneuronal Circuit in the Embryonic Spinal Cord

Emory University, Atlanta GA

Investigators

Abstract

Synaptic refinement is the process of pruning back an initially exuberant neuronal projection pattern. This process is thought to be important in allowing developing circuits to adjust to their environment and it eliminates the need to genetically specify every detail of a neuron's connectivity. This process has been studied extensively in excitatory neurons that set up topographic projections to another part of the nervous system (e.g. retinal map formed in the visual cortex). To understand the development of neural networks, however, of we must appreciate how both excitatory and inhibitory elements within a network develop. Recently, inhibitory neurons in the auditory system have been shown to refine their tonotopic projections, demonstrating that inhibitory refinement can occur. The functional meaning and the underlying mechanisms of inhibitory refinement are completely unknown. Further, it had been unknown whether locally projecting inhibitory interneurons undergo refinement. Dr. Wenner's lab has characterized the connections of a locally projecting inhibitory interneuron in the chick embryo spinal cord called the R-interneuron, and have shown that these R-interneurons refine their connections with spinal motoneurons. The PI proposes a set of experiments to assess the function of inhibitory refinement (objective 1) and test whether the refinement process of this inhibitory interneuron is dependent on spiking activity (objective 2) and inhibitory neurotransmitter signaling (objective 3). This will provide important information about the similarities and differences in inhibitory and excitatory synaptic plasticity during development. The study will give insights into how a developmental balance between excitatory and inhibitory systems is achieved, and a better understanding of why this developmental balance may not be realized in certain disease states. In addition, this project will foster education on several levels within and beyond the PI's lab. meeting. Although recently arrived at Emory University, Dr. Wenner has mentored undergraduate students, including those from underrepresented minorities, in his lab. Dr. Wenner also participates in Atlanta's Brain Awareness Month by visiting K-12 classrooms. The proposed project will allow scientific education for an undergraduate student, graduate student, and a postdoctoral fellow as they participate in research, publishing, and presenting to the local community, as well as an international community at the annual neuroscience