Trunk Sensorimotor Cortex Is Essential for Autonomous Weight-Supported Locomotion in Adult Rats Spinalized as P1/P2 Neonates

Abstract

Unlike adult spinalized rats, approximately 20% of rats spinalized as postnatal day 1 or 2 (P1/P2) neonates achieve autonomous hindlimb weight support. Cortical representations of mid/low trunk occur only in such rats with high weight support. However, the importance of hindlimb/trunk motor cortex in function of spinalized rats remains unclear. We tested the importance of trunk sensorimotor cortex in their locomotion using lesions guided by cortical microstimulation in P1/P2 weight-supporting neonatal spinalized rats and controls. In four intact control rats, lesions of hindlimb/trunk cortex caused no treadmill deficits. All spinalized rats lesioned in trunk cortex (n = 16: 4 transplant, 6 transect, 6 transect + fibrin glue) lost an average of about 40% of their weight support. Intact trunk cortex was essential to their level of function. Lesion of trunk cortex substantially increased roll of the hindquarters, which correlated to diminished weight support, but other kinematic stepping parameters showed little change. Embryonic day 14 (E14) transplants support development of the trunk motor representations in their normal location. We tested the role of novel relay circuits arising from the grafts in such cortical representations in E14 transplants using the rats that received (noncellular) fibrin glue grafting at P1/P2 (8 allografts and 32 xenografts). Fibrin-repaired rats with autonomous weight support also had trunk cortical representations similar to those of E14 transplant rats. Thus acellular repair and intrinsic plasticity were sufficient to support the observed features. Our data show that effective cortical mechanisms for trunk control are essential for autonomous weight support in P1/P2 spinalized rats and these can be achieved by intrinsic plasticity.

Functional and Anatomical Reorganization of the Sensory-Motor Cortex after Incomplete Spinal Cord Injury in Adult Rats

“…Improvement in limb placements during overground locomotion by both ipsilesional forelimbs and hindlimbs too may be driven by cortical plasticity. In the neonatally spinalized rats, sensorimotor cortex reorganizes to participate in overground locomotion (Giszter et al, 2008); in intact rats, the cortex is thought to have little role in this form of locomotion.…”

Teaching Adult Rats Spinalized as Neonates to Walk Using Trunk Robotic Rehabilitation: Elements of Success, Failure, and Dependence

“…With the exception of anesthetic method (we used isoflurane as opposed to hypothermia), spinal transection surgery is largely as described in detail in Miya et al (1997) and Giszter et al (1998Giszter et al ( , 2008a. Neonates were placed under isoflurane anesthesia and maintained on an anesthetic plane (0.75%-2% mixed in oxygen), and sterile procedures were used throughout the surgery.…”

“…This was accomplished in a manner similar to Miya et al (1997) and Giszter et al (1998) by determining the proportion of autonomous hindlimb weight-supporting steps (%WSS) taken compared with the sum of hindlimb steps attempted (i.e., sum of weight-supported and non-weight-supported steps) (Miya et al, 1997;Giszter et al, 1998). The classification we used here was based on observations (Giszter et al, 2008a; see Materials and Methods) that most NTX rats showed either good consistent weight-supported stepping of Ͼ50%WSS (weight-supporting NTX rats or WS, usually ϳ20% of rats prepared) or poor weight-supported stepping of Ͻ50%WSS, which was often accompanied with frequent hindlimb scissoring action (NWS) (Giszter et al, 2008a) (usually ϳ80% of rats prepared). In prior work, the WS and NWS rats generated after neonatal spinal transection differed in a range of ways, with a "no-man's land" between the function levels of 20%-25%WSS and 45%-50% or better WSS (Miya et al, 1997;Giszter et al, 1998Giszter et al, , 2007.…”

“…Understanding how to promote such weight support in the other NTX rats may help designing rehabilitation for complete SCI. We have analyzed coordinative mechanisms and spinal and cortical features enabling NTX weight support (Giszter et al, 1998(Giszter et al, , 2007(Giszter et al, , 2008a. A "wheelbarrow race" or "pantomime horse" model of function nicely describes NTX rats weight support performance despite complete transection (Giszter et al, 2010): trunk actions coordinate the two independent neural control systems using the coupled biomechanics fore and aft (Giszter et al, 2007(Giszter et al, , 2008b similar to a children's "wheelbarrow race."…”

“…We have analyzed coordinative mechanisms and spinal and cortical features enabling NTX weight support (Giszter et al, 1998(Giszter et al, , 2007(Giszter et al, , 2008a. A "wheelbarrow race" or "pantomime horse" model of function nicely describes NTX rats weight support performance despite complete transection (Giszter et al, 2010): trunk actions coordinate the two independent neural control systems using the coupled biomechanics fore and aft (Giszter et al, 2007(Giszter et al, , 2008b similar to a children's "wheelbarrow race." This coordination is likely a cortical mediated skill: there is a 1:1 relationship of specific trunk representations in motor cortex with higher function (Giszter et al, 1998(Giszter et al, , 2008a; lesion of these representations and trunk somatosensory overlap cortex abolishes high function (Giszter et al, 1998(Giszter et al, , 2008a; and specific biomechanical coordination associates with function (Giszter et al, 2007).…”