Inter- and intralimb adaptations to a sensory perturbation during activation of the serotonin system after a low spinal cord transection in neonatal rats

Abstract

Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during stepping, while the other half did not. Differences in stepping behavior (interlimb coordination) and limb trajectories (intralimb coordination) were found to occur in both intact and spinal subjects. Adaptations were seen in the forelimbs and hindlimbs. Also, real-time and persistent effects of ROM restriction (following removal of the perturbation) were seen in ROM-restricted subjects. This study demonstrates the sensitivity of the isolated spinal cord to sensory feedback in conjunction with serotonin modulation.

Range of motion (ROM) restriction influences quipazine-induced stepping behavior in postnatal day one and day ten rats

“…In general, experience with ROM restriction depressed the frequency of forelimb steps during the period in which it was imposed for P1 and P10 subjects. This replicates a previous study, which showed that P1 subjects decreased their forelimb stepping behavior while suspended over a Plexiglas substrate [16], and a recent study showing that spinal cord transected P10 rats (low thoracic spinal cord transection happened at P1) decrease their stepping behavior as well [31]. …”

“…Both real-time and persistent effects were observed in limb trajectories for P1 and P10 pups that received ROM restriction. This coincides with research in young humans and animals that shows that immature locomotor systems can adapt intralimb coordination to sensory feedback both during and after training [22, 29, 31, 32]. …”

“…Both P1 and P10 pups showed an increase in coordinated movement (i.e., alternated and synchronized steps) as a result of treatment with the 5-HT 2 agonist quipazine, which has been shown in previous research with perinatal and adult rats to primarily increase alternated stepping [11, 12, 15, 16, 31]. Interestingly, a difference was found in the number and time course of quipazine-induced steps between P1 and P10, with P10 pups showing fewer steps and only maintaining a high frequency of steps during the first 15 minutes following treatment with quipazine, compared to P1 pups.…”

“…Immediately following the injection, a 15-min ROM (range of motion) restriction was imposed for half of the subjects. To induce ROM restriction, a piece of Plexiglas was placed beneath the subject’s limbs at 50% of limb length when the limbs were fully extended [31]. The Plexiglas plate was supported by a clamp attached to an adjacent vertical bar.…”

“…Quipazine-induced stepping was examined in postnatal day 1 (P1; 24 hours after birth) and P10 rats during and after a period of altered sensory feedback using ROM (range of motion) restriction. ROM restriction was enforced by placing a stiff substrate (Plexiglas plate) at a distance of 50% of limb length from the body [31], thus limiting the range of motion available during quipazine-induced stepping behavior. Persistent effects of the ROM restriction were investigated here to see if the perturbation produced a change in subsequent motor behavior, after the ROM restriction was removed.…”