Canadian Institutes of Health Research Group in Sensory-Motor Systems

REGULATION OF SPINAL INTERNEURON INPUT/OUTPUT FUNCTIONS

                This is an integrated proposal that combines the expertise of our lab in computational models of single neuron function with the unique skills of members of Dr. Robert Fyffe’s lab (Wright State University, Ohio; www.med.wright.edu/cbr/) in quantitative light and electron microscopy, immunocytochemistry, and  electrophysiology.

                The long-term goal of this project is to define the structural and functional properties that underly the integrative functions and general excitability of spinal cord interneurons involved in the control of locomotion and posture in mammals. Superficially, a great deal is known about spinal interneurons in general, and about certain classes of interneurons in particular. Their pivotal role(s) in motor control are well recognized, as is the notion that changes in interneuron excitability are likely to be contributing factors in a variety of locomotor and postural disturbances consequent to disease or trauma.  But critical details of the functional and structural architecture of interneurons are lacking, particularly concerning the mode of action of descending control systems and cellular input-output characteristics. These gaps are a significant impediment in designing studies of the effects of spinal injury and the cellular/network mechanisms that underlie the resulting functional impairments.

                Although different classes of interneurons may share some common features, it is accepted, but not well documented, that there exist striking differences in synaptology, receptor and ion channel expression, and, of course, dendritic structure and axonal connectivity patterns. It is our hypothesis that such diversity is functionally meaningful, and as a consequence provides different classes of cells with a broad repertoire of input/output fumctions. Thus, we believe it is essential to perform a focussed and intensive study of the structural and functional architecture of identified interneurons at the cellular level. Specific hypotheses and goals are:

1) Dendritic structure and synapse distribution are two of the key factors that determine the relative amount of synaptic current that reaches the cell soma and controls cell firing. 

To test these hypotheses we will determine the input-output properties of physiologically-identified interneurons, using computer models based on detailed measurement of interneuronal dendritic geometry and innervation.

2) Different classes of ventral horn interneurons are differentially innervated by descending motor control systems and display unique patterns of synaptic organization.

We will determine:

A) the synaptic relationships between neurochemically- and anatomically-identified descending control systems and identified interneurons and

B) the density and ultrastructural features of synaptic inputs that converge on the soma, dendrites and axon initial segment of identified interneurons.