Spike timing-dependent plasticity in the adult rat with chronic cervical spinal cord contusion

Authors: *N. DE LA OLIVA1, A. E. HAGGERTY1, M. A. PEREZ1,2, M. OUDEGA1,2,3,4;
1 Miami Project To Cure Paralysis, Univ. of Miami, Miami, FL;
2 Bruce W. Carter Dept. of Veterans Affairs Med. Ctr., Miami, FL;
3 Affiliated Cancer Hosp. & Inst. of Guangzhou Med.Univ., Guangzhou, China;
4 Neurolog. Surgery, Miller Sch. of Medicine, Univ. of Miami, Miami,FL

Lab Abstract: Spinal cord injury (SCI) damages descending and ascending axons resulting in motor and sensory function impairments. Histological and electrophysiological data revealed that in most SCI patients residual axonal connections between the brain and the spinal cord below the injury exist, which opens avenues for neuromodulatory therapies for recovering function. electrical stimulation of residual axonal connections is a promising strategy to recover lost function. Repetitive electrical stimulation results in persistent increase or decrease of synaptic efficacy (i.e., long-term potentiation or depression, respectively). Previous studies demonstrated that the arrival of repeated pairs of precisely timed presynaptic and postsynaptic action potentials to a given synapse changes synaptic strength. This process is known as spike timing-dependent plasticity (STDP). The direction of the effects of STDP stimulation protocols depends on the spike order and time between the central and peripheral stimuli, as well as on the frequency and duration of the stimulation. Importantly, it was shown that STDP protocols can enhance motor function after paired corticospinal tract (CST) and peripheral nerve stimuli in people with and without SCI, although with transient effects. In this study, we aimed to elucidate the cellular and molecular mechanisms underlying STDP aftereffects in a cervical SCI rat model. First, we traced the CST and the reticulospinal tract (RST), which are both involved in forelimb reach and grasp behavior in rats, along with the motoneurons of targeted forelimb muscles, to evaluate the spinal connections before and after 12 weeks C5 chronic injury. Based on these results, an STDP stimulation protocol was applied to maximize the synaptic strength in those connections. Electrophysiological and histological techniques were used to evaluate changes after the stimulation. We hypothesize that higher frequency and longer stimulation will result in longerlasting functional and cellular aftereffects. The ultimate goal is to use the data from our animal studies to improve the efficacy of STDP protocol on improving function in SCI patients.

Program #/Poster #: 051.18/H4
Topic: C.11. Spinal Cord Injury and Plasticity
Support: VA Grant I01BX007080
Society for Neuroscience

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