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.
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.
|Ferré, Sergi; Díaz-Ríos, Manuel; Salamone, John D et al. (2018) New Developments on the Adenosine Mechanisms of the Central Effects of Caffeine and Their Implications for Neuropsychiatric Disorders. J Caffeine Adenosine Res 8:121-131|
|Delgado-Vélez, Manuel; Lasalde-Dominicci, José A (2018) The Cholinergic Anti-Inflammatory Response and the Role of Macrophages in HIV-Induced Inflammation. Int J Mol Sci 19:|
|Rivera-Oliver, Marla; Moreno, Estefanía; Álvarez-Bagnarol, Yocasta et al. (2018) Adenosine A1-Dopamine D1 Receptor Heteromers Control the Excitability of the Spinal Motoneuron. Mol Neurobiol :|
|Capó-Vélez, Coral M; Delgado-Vélez, Manuel; Báez-Pagán, Carlos A et al. (2018) Nicotinic Acetylcholine Receptors in HIV: Possible Roles During HAND and Inflammation. Cell Mol Neurobiol :|
|Saxena, Manoj; Delgado, Yamixa; Sharma, Rohit Kumar et al. (2018) Inducing cell death in vitro in cancer cells by targeted delivery of cytochrome c via a transferrin conjugate. PLoS One 13:e0195542|
|Thapa, Bibek; Diaz-Diestra, Daysi; Santiago-Medina, Carlene et al. (2018) T1- and T2-weighted Magnetic Resonance Dual Contrast by Single Core Truncated Cubic Iron Oxide Nanoparticles with Abrupt Cellular Internalization and Immune Evasion. ACS Appl Bio Mater 1:79-89|
|Vaasjo, Lee O; Quintana, Alexandra M; Habib, Mohamed R et al. (2018) GABA-like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase-like immunoreactivity in the feeding motor systems of panpulmonate snails. J Comp Neurol 526:1790-1805|
|Capó-Vélez, Coral M; Morales-Vargas, Bryan; García-González, Aurian et al. (2018) The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders. Sci Rep 8:1829|
|Colón, Jennifer M; González, Pablo A; Cajigas, Ámbar et al. (2018) Continuous tamoxifen delivery improves locomotor recovery 6h after spinal cord injury by neuronal and glial mechanisms in male rats. Exp Neurol 299:109-121|
|Alicea, Daniel; Perez, Marizabeth; Maldonado, Carolina et al. (2017) Cortactin Is a Regulator of Activity-Dependent Synaptic Plasticity Controlled by Wingless. J Neurosci 37:2203-2215|
Showing the most recent 10 out of 82 publications