The focus of research in our lab is on the role of neural circuits in the mammalian spinal cord for the control of movement. We are interested in both basic and clinical research. The latter is aimed at understanding the impairment of spinal circuits in spasticity, which develops following injuries to the spinal cord. A variety of techniques are utilized, ranging from single electrode voltage clamp studies of spinal motoneurons to extracellular recordings of discharge patterns of spinal interneurons to measurements of mechanical behaviors of muscle fibers and whole muscles.
We have also developed computer simulations that use our data measured in individual cells to realistically reconstruct the behavior of entire neural networks controlling motor output. Recently, we developed a reversible spinal lesion using cooling of the upper surface of the cord, allowing intracellular recording from single neurons both before and after this acute spinal injury. This technique has allowed us to identify promising new pharmacological agents to control spasticity.
Our primary goal at present is to use voltage clamp techniques and highly specific pharmacological blockers to identify the contributions of voltage-sensitive channels in the dendrites of spinal neurons to motor output.

Figure: Amplification and prolongation of synaptic input by a persistent inward current in the dendrites of a motoneuron.

All motor commands pass through motoneurons in the spinal cord or brainstem. Motoneuron axons then innervate muscle fibers to generate force. Traditionally motoneurons have been considered to be passive followers of motor commands. However, it has recently been shown that the dendrites of motoneurons contain L-type calcium channels that are voltage-sensitive and highly persistent - that is, once activated, these channels tend to stay open.

Thus, when a synaptic input is applied to the motoneuron, the persistent inward current from the L-type channel markedly amplifies the synaptic current while the input is maintained and then continues to generate current on its own after the input ceases (see the bottom trace in the figure; current measured during voltage clamp).

Alternatively, if voltage is allowed to change in response to the input, the persistent inward current produces a sustained plateau potential (middle trace - action potentials in this cell have been eliminated by the intracellular sodium channel blocker QX-314). If the cell is allowed to discharge action potentials normally, the persistent inward current produces strong firing during the input and then generates self-sustained firing for a long period after the input ends.

Therefore, the motoneuron can dramatically alter the motor commands it receives. (The synaptic input for all traces in this figure was generated by steady firing in sensory axons from muscle spindles.The upper and lower traces are taken from the same cell; the middle trace is from a different cell and experiment).