Research Project
10296742
Project Summary/Abstract The inability to maintain upright body posture and balance is one of the major motor disorders following spinal cord injury (SCI). In our previous, NIH-supported studies, specific distortions in operation of spinal postural mechanisms (networks) underlying each of three main phenomena related to SCI ? spinal shock, the development of spasticity, and the recovery of postural functions have been demonstrated in an animal model (rabbit). We also demonstrated a crucial role of supraspinal postural networks in control of posture. A general goal of the present project is to explain effects of SCI on postural functions on the basis of SCI-caused changes in the operation of the corresponding supraspinal neuronal postural networks. Clinical data suggest that most SCIs are incomplete. Incomplete SCIs cause severe distortions in the interaction between the brain and the spinal cord. This leads to a dramatic decrease or asymmetry of muscle tone and postural limb reflexes resulting in the inability to stand and maintain balance. Our Aim 1 is to analyze the effects of incomplete SCIs (lateral and dorsal hemisection, LHS and DHS) on the operation of supraspinal postural networks, and to explain postural deficits by the changes in the activity of specific ascending and descending pathways. We have developed a novel technique that allows to perform ?reversible LHS or DHS? repeatedly many times. This allows studying postural responses and the activity of individual neurons of the ascending and descending pathways under two conditions: (i) when the brain is connected to the spinal cord and (ii) during LHS or DHS, when the connection between the spinal cord and the brain through lateral or dorsal pathways, respectively, is temporarily blocked. Previously we have shown that, after DHS and LHS, postural functions recover in a few weeks. Our Aim 2 is to analyze the activity of supraspinal postural networks in recovered LHS- and DHS- subjects, and to explain the recovery by changes in the activity of specific populations of ascending and descending neurons. For this purpose, we will (i) record the activity of individual neurons of the supraspinal postural networks during postural performance in recovered LHS- and DHS-subjects, and (ii) compare the results with those obtained in intact subjects and in subjects after acute LHS and DHS. Our Aim 3 is to analyze the role of different descending pathways in control of specific aspects of postural behavior in recovered LHS- and DHS-subjects, and to explain the recovery by the changes in the functional role of particular pathways. For this purpose, the effects of the chemogenetic activation/inactivation of different supraspinal pathways on the performance of various postural tasks in intact and recovered LHS- and DHS-subjects will be compared. This study will provide unique information about the SCI-caused changes in the activity of supraspinal neuronal networks, which are responsible for the motor deficits, as well as about the changes underlying functional recovery in subjects with incomplete SCI. This information is clinically relevant as a basis for designing new rehabilitation strategies for recuperating postural functions in patients with postural deficits.
