Integrative function in the dorsal horn is mediated through complex neural circuits formed by synaptic connections between interneurons having diverse physiological and neurochemical properties. Work in our laboratory has contributed to a better understanding of these properties and shed light on fundamental mechanisms underlying neuronal connectivity in this important region. Our past studies have elucidated intrinsic signaling properties of local interneurons and organization of their connections, information that is crucial for understanding how sensory information is transformed under normal circumstances, and how it can be disturbed when normal function is disrupted.
The specific aims of the renewal period build upon our previous work and test the general hypotheses that: i) synaptic connections between dorsal horn interneurons exhibit short-term activity-dependent fluctuations that influence integration of sensory information in local neural networks and ii) dorsal horn interneurons may have multiple actions at the same synapse and that function at these connections can be differentially regulated by level of presynaptic activity. Accordingly, the following Specific Aims are proposed: 1) Determine properties of short-term facilitation and depression of connections between dorsal horn interneurons. 2) Identify local circuit neurons with presumptive dual excitatory and inhibitory functions. 3) Determine postsynaptic actions of putative 'dual function' lamina II synapses.
These Aims will be accomplished using in vitro preparations of rodent spinal cord. Short-term plasticity and function of individual synaptic connections between neurons will be investigated using a combination of dual recording techniques, pharmacological analyses and confocal microscopic analyses of immunostaining at the single neuron level. The studies will provide essential information about dynamic modulation of synaptic function underlying spinal integration of innocuous and noxious sensory information.
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