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Canadian Institutes of Health Research Group in Sensory-Motor Systems


     The axons of spinal motoneurons provide the sole link between all premotor pathways and the effectors for movement: skeletal muscles.  This special role was recognized almost 100 years ago by Sherrington (1906), who enshrined this role by describing the motoneuron as the ‘final common pathway’.  The term ‘common’ emphasizes that each spinal motoneuron receives tens of thousands of synapses from many different pathways.  Yet, with few exceptions, the actions of these pathways have been studied with the assumption that their effect on motoneuron activity is independent of the activity in other pathways.  This custom ignores two fundamental features of motoneurons: 1) synaptic activity on the dendrites will cause large changes in driving potential and, therefore, summation of synaptic currents may be highly sub-linear; 2) synaptic activity may activate or inactivate  voltage-dependent channels on the dendrites and the current from these channels may boost or reduce synaptic currents generated by other pathways.  This proposal is founded on the hypothesis that the integrative capacity of motoneurons is not limited to simple linear summation of synaptic inputs.  Instead, due to local changes in driving potential and activation or inactivation of voltage-dependent channels, motoneurons can adjust their input/output properties depending on the spatial distribution of the active synapses.

Specific Hypotheses

     The influence of non-linear summation of synaptic currents on motoneuron input/output properties is poorly understood.  Quantitative measurements of non-linear summation are rare and can only be interpreted in the context of a detailed knowledge of the dendritic distribution of the active synapses.  Moreover, the measurements may be confounded by simultaneous activation of voltage-dependent channels.  Thus, the first two series of experiments will address the following hypotheses:

1)  In the absence of voltage-dependent channels, summation of synaptic currents generated by functionally related pathways can be sub-linear.  The magnitude of the sub-linearity depends on the distribution of the active  synapses on the dendritic tree.

2)  Voltage-dependent potassium and Ih channels are activated by synaptic currents on the dendritic tree and act to moderate changes in driving potential, leading to linear summation of synaptic currents reaching the soma.

The final series of experiments are designed to test the hypotheses that:

3)  Tonic stimulation of serotonergic neurons in the caudal raphe nuclei amplifies synaptic currents.  The amplification depends on the relative distribution of serotonergic synapses and the synapses responsible for the synaptic currents.


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Updated Aug 9, 2001