Developmental Changes in Locomotion and Sensorimotor Reflexes Following Spinal Cord Transection.

The developmental trajectory of weight-bearing locomotion and sensorimotor reflexes following a spinal cord injury, as well as the mechanisms for plasticity, remain unclear. In rats, the second postnatal week is a critical period for the development and recovery of spinal sensorimotor function. The purpose of the present study was to characterize developmental changes during this time frame to provide a basis for potential interventions and future research.

Epigenetic processes associated with neonatal spinal transection.

In early development, the spinal cord in healthy or disease states displays remarkable activity-dependent changes in plasticity, which may be in part due to the increased activity of brain derived neurotrophic factor (BDNF). Indeed, BDNF delivery has been efficacious in partially ameliorating many of the neurobiological and behavioral consequences of spinal cord injury (SCI), making elucidating the role of BDNF in the normative developing and injured spinal cord a critical research focus. Recent work in our laboratory provided evidence for aberrant global and locus-specific epigenetic changes in methylation of the Bdnf gene as a consequence of SCI.

Visualization of rat tendon in three dimensions using micro-Computed Tomography.

Micro-computed tomography (CT) is an X-ray-based imaging modality that produces three-dimensional (3D), high-resolution images of whole-mount tissues, but is typically limited to dense tissues, such as bone. The X-rays readily pass-through tendons, rendering them transparent. Contrast-enhancing chemical stains have been explored, but their use to improve contrast in different tendon types and across developmental stages for micro-CT imaging has not been systematically evaluated.

A preliminary investigation of high retinoic acid exposure during fetal development on behavioral competency and litter characteristics in newborn rats.

Myelomeningocele (MMC) is the most common and severe type of spina bifida in which the developing spine and neural tube fail to close during prenatal development. This typically results in a small portion of the lower spinal cord and meninges protruding from the back of the individual, accompanied by severe motor and sensory deficits. In rats, retinoic acid (RA) exposure in high doses during fetal development has been shown to induce morphologic and clinical symptoms similar to humans with MMC.

Acute intrathecal administration of quipazine elicits air-stepping behavior.

Serotonin plays a pivotal role in the initiation and modulation of locomotor behavior in the intact animal, as well as following spinal cord injury. Quipazine, a serotonin 2 receptor agonist, has been used successfully to initiate and restore motor behavior in rodents. Although evidence suggests that the effects of quipazine are spinally mediated, it is unclear whether intrathecal (IT) quipazine administration alone is enough to activate locomotor-like activity or whether additional stimulation is needed.

Neonatal Spinal Cord Transection Decreases Hindlimb Weight-Bearing and Affects Formation of Achilles and Tail Tendons.

Mechanical loading may be required for proper tendon formation. However, it is not well understood how tendon formation is impacted by the development of weight-bearing locomotor activity in the neonate. This study assessed tendon mechanical properties, and concomitant changes in weight-bearing locomotion, in neonatal rats subjected to a low thoracic spinal cord transection or a sham surgery at postnatal day (P)1.

Pericytes improve locomotor recovery after spinal cord injury in male and female neonatal rats.

Objective: It is not known how activation of the hypoxia-inducible factor (HIF) pathway in pericytes, cells of the microvascular wall, influences new capillary growth. We tested the hypothesis that HIF-activated pericytes promote angiogenesis in a neonatal model of spinal cord injury (SCI).

Methods: Human placental pericytes stimulated with cobalt chloride and naïve pericytes were injected into the site of a thoracic hemi-section of the spinal cord in rat pups on postnatal day three (P3).

A Cohort Study of Relations Among Caregiver-Infant Co-Occupation and Reciprocity.

Co-occupation is the mutual engagement of two people in a shared occupation. Recent research has investigated co-occupational activities during sensitive periods to inform clinical practice. However, there remains a dearth of applied research to bridge gaps between research and practice within salient co-occupational relationships between caregivers and infants.

Low-cost, open-source, variable speed and incline treadmill for studying impacts of neonatal locomotion.

There is a need for a small-scale, laboratory treadmill to investigate impacts of neonatal locomotion on neuromuscular and musculoskeletal development in small animal models. Adult mice and rats are routinely assessed using commercially available treadmills, but these treadmills can be relatively expensive and they may lack features needed to evaluate developing animals. Therefore, to overcome these limitations, a new treadmill was designed, built and calibrated.

Onset of neonatal locomotor behavior and the mechanical development of Achilles and tail tendons.

Tendon tissue engineering approaches are challenged by a limited understanding of the role mechanical loading plays in normal tendon development. We propose that the increased loading that developing postnatal tendons experience with the onset of locomotor behavior impacts tendon formation. The objective of this study was to assess the onset of spontaneous weight-bearing locomotion in postnatal day (P) 1, 5, and 10 rats, and characterize the relationship between locomotion and the mechanical development of weight-bearing and non-weight-bearing tendons.

DNA methylation and behavioral changes induced by neonatal spinal transection.

Although the importance of epigenetic mechanisms in behavioral development has been gaining attention in recent years, research has largely focused on the brain. To our knowledge, no studies to date have investigated epigenetic changes in the developing spinal cord to determine the dynamic manner in which the spinal epigenome may respond to environmental input during behavioral development. Animal studies demonstrate that spinal cord plasticity is heightened during early development, is somewhat preserved following neonatal transection, and that spinal injured animals are responsive to sensory feedback.

The Spinal Cord, Not to Be Forgotten: the Final Common Path for Development, Training and Recovery of Motor Function.

Research on learning, memory, and neural plasticity has long focused on the brain. However, the spinal cord also exhibits these phenomena to a remarkable degree. Following a spinal cord injury, the isolated spinal cord in vivo can adapt to the environment and benefit from training.

Locomotion and posture development in immature male and female rats (Rattus norvegicus): Comparison of sensory-enriched versus sensory-deprived testing environments.

The aim of the current study was to provide normative data on spontaneous locomotion and posture behavior in developing rats (Rattus norvegicus), during the first 2 postnatal weeks. Male and female rat pups were tested daily from P1 (postnatal day 1; ∼24 hr after birth) to P15 in a sensory-enriched or sensory-deprived testing environment, which was enclosed in a temperature-controlled incubator. Pups in the sensory-deprived condition were tested individually and placed in a square, Plexiglas box (open-field) for a 20-min test period.

Responsiveness of rat fetuses to sibling motor activity: Communication in utero?

Previous research has revealed that fetuses detect and respond to extrauterine stimuli such as maternal movement and speech, but little attention has been cast on how fetuses may directly influence and respond to each other in the womb. This study investigated whether motor activity of E20 rat fetuses influenced the behavior of siblings in utero. Three experiments showed that; (a) contiguous siblings expressed a higher frequency of synchronized movement than noncontiguous siblings; (b) fetuses that lay between two siblings immobilized with curare showed less movement relative to fetuses between saline or uninjected controls; and (c) fetuses between two siblings behaviorally activated by the opioid agonist U50,488 also showed less activity and specific behavioral changes compared to controls.

Histamine modulates spinal motoneurons and locomotor circuits.

Spinal motoneurons and locomotor networks are regulated by monoamines, among which, the contribution of histamine has yet to be fully addressed. The present study investigates histaminergic regulation of spinal activity, combining intra- and extracellular electrophysiological recordings from neonatal rat spinal cord in vitro preparations. Histamine dose-dependently and reversibly generated motoneuron depolarization and action potential firing.

Stimulation of 5-HT2A receptors recovers sensory responsiveness in acute spinal neonatal rats.

Quipazine is a 5-HT-receptor agonist that has been used to induce motor activity and promote recovery of function after spinal cord injury in neonatal and adult rodents. Sensory stimulation also activates sensory and motor circuits and promotes recovery after spinal cord injury. In rats, tail pinching is an effective and robust method of sacrocaudal sensory afferent stimulation that induces motor activity, including alternating stepping.

Multilevel Analysis of Locomotion in Immature Preparations Suggests Innovative Strategies to Reactivate Stepping after Spinal Cord Injury.

Locomotion is one of the most complex motor behaviors. Locomotor patterns change during early life, reflecting development of numerous peripheral and hierarchically organized central structures. Among them, the spinal cord is of particular interest since it houses the central pattern generator (CPG) for locomotion.

Serotonergic activation of locomotor behavior and posture in one-day old rats.

The purpose of this study was to determine what dose of quipazine, a serotonergic agonist, facilitates air-stepping and induces postural control and patterns of locomotion in newborn rats. Subjects in both experiments were 1-day-old rat pups. In Experiment 1, pups were restrained and tested for air-stepping in a 35-min test session.

Posture effects on spontaneous limb movements, alternated stepping, and the leg extension response in neonatal rats.

The development of postural control is considered an important factor for the expression of coordinated behavior such as locomotion. In the natural setting of the nest, newborn rat pups adapt their posture to perform behaviors of ecological relevance such as those related to suckling. The current study explores the role of posture in the expression of three behaviors in the newborn rat: spontaneous limb activity, locomotor-like stepping behavior, and the leg extension response (LER).

Developmental plasticity of coordinated action patterns in the perinatal rat.

Some of the most simple, stereotyped, reflexive, and spinal-mediated motor behaviors expressed by animals display a level of flexibility and plasticity that is not always recognized. We discuss several examples of how coordinated action patterns have been shown to be flexible and adaptive in response to sensory feedback. We focus on interlimb and intralimb coordination during the expression of two action patterns (stepping and the leg extension response) in newborn rats, as well as interlimb motor learning.

Sensorimotor training during expression of the leg extension response (LER) in 1-day-old rats.

In newborn rats, the leg extension response (LER) is a coordinated hyperextension of the hindlimbs that is shown in response to anogenital stimulation. Here we examined the influence of sensorimotor training on LER expression in postnatal day 1 rats. In Experiment 1, we examined if proprioceptive feedback facilitates LER expression.

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

Previous research has shown that neonatal rats can adapt their stepping behavior in response to sensory feedback in real-time. The current study examined real-time and persistent effects of ROM (range of motion) restriction on stepping in P1 and P10 rats. On the day of testing, rat pups were suspended in a sling.