Mechanisms of rebound excitation following spinal cord stimulation

Spinal cord stimulation (SCS) is currently a promising therapeutic approach for spinal cord injury (SCI). However, it does not generate enough muscle activation in some patients to enable them to stand and step. The ultimate goal of this proposal is to enhance the effectiveness of SCS in patients with SCI. Our studies have uncovered a new type of response to SCS, a potent post-stimulation rebound excitation (PSRE) evoked immediately following the stimulation train. PSRE is directed solely to extensor muscles, and is highly controllable via changing stimulation parameters. Therefore, it has great clinical potential to assist postural movements, such as sit-to-stand transitions. The proposed study characterizes this new behavior and defines criteria for consistently evoking it. Our preliminary investigations of PSRE mechanisms show that it involves an excitatory synaptic current mediated by interneurons. In order to determine the circuit mechanisms, we plan to combine intracellular recording of motoneuron with intraspinal microelectrode arrays to record interneuronal activity during PSRE. We are also examining the role of intrinsic motoneuron properties. The PSRE has not been previously seen because most studies of SCS rely on anesthetized preparation in which spinal networks are continually suppressed by anesthesia. Our work utilizes the decerebrate unanesthetized cat preparation, which has the advantage of intact and active brainstem neuromodulatory systems. This neuromodulation is fundamental to the excitability of spinal neurons in normal movements. In fact, PSRE disappeared after acute transection of the spinal cord at the T12 thoracic segment, which is most probably due to loss of descending neuromodulation. Although, motoneuron excitability has been shown to recover following chronic SCI, PSRE was not restored after chronic (1 month) spinal transection in the cat. In this proposal, we examine pharmacological neuromodulators that can restore PSRE after SCI.