The long-term goal of this project is to understand the neural mechanisms of local synaptic circuits in the spinal dorsal horn that play vital roles in mediating segmental reflexes and integrating diverse types of incoming sensory information. In the next 3 years we propose to test the general hypothesis that neural networks are assembled from groups of interneurons expressing signature membrane properties and connectivity patterns that correlate with their mechanosensory input. Determining the functional and structural basis of these networks is essential for understanding central mechanisms that underlie long-term alteration of sensory and reflex function and contribute to neuropathic pain syndromes.
The specific aims are to: l) Determine if interneurons that process specific mechanosensory modalities have intrinsic firing properties and ionic conductances different from interneurons that process other modalities. 2) Determine whether differential expression of ionic conductances in interneurons is related to differences in firing properties and/or axonal organization. 3) Determine the characteristics of synaptic transmission between individual pre- and postsynaptic neurons and identify the synaptic mediators involved. 4) Investigate plastic changes in interneuron firing properties and synaptic linkage. An integrated series of in vitro experiments are planned utilizing a unique rodent spinal cord preparation that allows functional identification of sensory inputs. Local circuit interneurons are studied using whole-cell recording methodology and are identified according to their axonal connections and functional inputs. Pharmacological techniques and immunohistochemical staining are used to provide data about the chemical neuroanatomy of network neurons. The results will contribute to a better understanding of network function in spinal cord neuropathies and will provide a blueprint for future efforts to model network information processing in the dorsal horn.
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