The basic motor patterns driving the rhythmic movements of our lower limbs during walking are generated by groups of neurons termed central pattern generators (CPGs) which are located within the spinal cord. The Iocomotor CPG is strongly influenced by timing information from ongoing afferent feedback, particularly those provided by hip flexion and limb loading, but also by more specialized 'resetting'responses (e.g. stumble-corrective). After a complete thoracic spinal cord injury (SCI), control of the hindlimb CPG is wholly dependent on remaining sensory afferent activity patterns, and under the right conditions, the sensorimotor transformations are so well encoded that treadmill locomotion in the adult rat is almost indistinguishable from a normal animal (Courtine et al. 2009). Limb afferent feedback alone was able not only to encode treadmill speed changes, but also produced movement synergies needed for sideways and backward stepping. The spinalized thoracolumbar neonatal rat spinal cord can be maintained in vitro with the hindlimbs attached. While the neonate is incapable of weight bearing locomotion, the isolated in vitro preparation is capable of generating complex hindlimb locomotor patterns with motor synergies that are surprisingly similar to those observed electromyographically and kinematically in the adult. If the afferent encoding properties are also similar at this age, there is an opportunity to study afferent control of locomotor spinal networks with the mechanistic strength on an in vitro preparation. We have developed a neonatal mouse locomotor preparation that features an optimized peripheral nerve dissection for selective stimulation of cutaneous and muscle afferents and are thus in an unprecedented position to characterize afferent actions on the CPG. Advances in our understanding of sensory input on movement control will allow us to define more precisely the requirements for the rehabilitation of patients with SCI. There is increasing evidence that in order to treat patients that have suffered an SCI more effectively, therapeutic strategies should include a combination sensory afferent stimulation techniques (e.g. epidural stimulation) and assisted physical therapy. Our findings will have direct implications for better designing these therapeutic strategies designed to take advantage of the plasticity of the spinal CPG network for locomotion.

Public Health Relevance

A detailed understanding of the pathways enabling sensory-motor transformations during locomotion promises to provide a roadmap for designing effective interventions to promote locomotor function following SCI. The advantage of this animal model system is the ability to use approaches and technologies that promise to greatly accelerate our discovery of these essential pathways.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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University of Puerto Rico Med Sciences
San Juan
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Padilla-Morales, Luis F; Colón-Sáez, José O; González-Nieves, Joel E et al. (2016) Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology. Data Brief 6:433-7
Duprey-Díaz, Mildred V; Blagburn, Jonathan M; Blanco, Rosa E (2016) Exogenous Modulation of Retinoic Acid Signaling Affects Adult RGC Survival in the Frog Visual System after Optic Nerve Injury. PLoS One 11:e0162626
Melendez, Roberto I; Roman, Cristina; Capo-Velez, Coral M et al. (2016) Decreased glial and synaptic glutamate uptake in the striatum of HIV-1 gp120 transgenic mice. J Neurovirol 22:358-65
Colón, Jennifer M; Torrado, Aranza I; Cajigas, Ámbar et al. (2016) Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats. J Neurotrauma 33:1696-708
Ramos, Félix M; Delgado-Vélez, Manuel; Ortiz, Ángel L et al. (2016) Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder. J Neurovirol 22:327-35
Nogueras-Ortiz, Carlos; Yudowski, Guillermo A (2016) The Multiple Waves of Cannabinoid 1 Receptor Signaling. Mol Pharmacol 90:620-626
Morales-Cruz, Moraima; Cruz-Montañez, Alejandra; Figueroa, Cindy M et al. (2016) Combining Stimulus-Triggered Release and Active Targeting Strategies Improves Cytotoxicity of Cytochrome c Nanoparticles in Tumor Cells. Mol Pharm 13:2844-54
Báez-Pagán, Carlos A; Del Hoyo-Rivera, Natalie; Quesada, Orestes et al. (2016) Heterogeneous Inhibition in Macroscopic Current Responses of Four Nicotinic Acetylcholine Receptor Subtypes by Cholesterol Enrichment. J Membr Biol 249:539-49
Martinez, Namyr A; Ayala, Alondra M; Martinez, Magdiel et al. (2016) Caveolin-1 Regulates the P2Y2 Receptor Signaling in Human 1321N1 Astrocytoma Cells. J Biol Chem 291:12208-22

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