Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system

Associations between Quantitative Mobility Measures Derived from Components of Conventional Mobility Testing and Parkinsonian Gait in Older Adults

Objective: To provide objective measures which characterize mobility in older adults assessed in the community setting and to examine the extent to which these measures are associated with parkinsonian gait. Methods: During conventional mobility testing in the community-setting, 351 ambulatory non-demented Memory and Aging Project participants wore a belt with a whole body sensor that recorded both acceleration and angular velocity in 3 directions. We used measures derived from these recordings to quantify 5 subtasks including a) walking, b) transition from sit to stand, c) transition from stand to sit, d) turning and e) standing posture. Parkinsonian gait and other mild parkinsonian signs were assessed with a modified version of the original Unified Parkinson’s Disease Rating Scale (mUPDRS). Results: In a series of separate regression models which adjusted for age and sex, all 5 mobility subtask measures were associated with parkinsonian gait and accounted for 2% to 32% of its variance. When all 5 subtask measures were considered in a single model, backward elimination showed that measures of walking sit to stand and turning showed independent associations with parkinsonian gait and together accounted for more than 35% of its variance. Cross-validation using data from a 2nd group of 258 older adults showed similar results. In similar analyses, only walking was associated with bradykinesia and sway with tremor. Interpretation Quantitative mobility subtask measures vary in their associations with parkinsonian gait scores and other parkinsonian signs in older adults. Quantifying the different facets of mobility has the potential to facilitate the clinical characterization and understanding the biologic basis for impaired mobility in older adults

Nucleus Retroambiguus Projections To Lumbosacral Mononeuronal Cell Groups In The Male Cat.

Recently, in the female cat, nucleus retroambiguus (NRA) projections have been described as distinct motoneuronal cell groups in the lumbar enlargement, possibly involved in lordosis behavior. The present study deals with the NRA-lumbosacral pathway in the male cat. Lumbosacral injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were made to localize and quantify retrogradely labeled neurons in the caudal medulla. These injections were preceded by spinal hemisections to distinguish between neurons with ipsi- and contralaterally descending axons. The NRA-lumbosacral fibers descended almost exclusively contralaterally, but neurons in areas surrounding the NRA projected mainly ipsilaterally. Injections of WGA-HRP werc made in the region of the NRA to determine its targets in the lumbosacral cord. To distinguish between the contralateral NRA pathways and the ipsilateral projections from neurons in the adjoining lateral tegmentum, the injections were preceded by ipsilateral hemisections in C2. A new scaling method was used to compare the results of the different cases, despite variations in size and segmental organization. The results show that the distribution pattern of anterogradely labeled fibers in the lumbosacral cord matched precisely the location of certain motoneuronal cell groups. The NRA projected densely to the abdominal wall and pelvic floor rnotoneurons in Onuf's nucleus, moderately to adductor longus, semimembranosus, and biceps femoris anterior motoneuronal cell groups, and only sparsely to iliopsoas and semitendinosus motoneuronal cell groups. Compared with the findings in the female, the NRA in the male cat projects more heavily to the biceps anterior and adductor lolgus and only sparsely to the iliopsoas and semitendinosus motoneuronal cell groups. These male-female differences are discussed.

Large Segmental Differences In The Spinal Projections To The Periaqueductal Gray In The Cat

The periaqueductal gray (PAG) is involved in motor activities, such as movements of the neck, back and hind limbs, cardiovascular regulation, micturition, vocalization, and mating behavior, as well as in nociception control. To accomplish these functions the PAG uses information from other parts of the limbic system, from the lower brainstem, and from the spinal cord. To study the ascending projections from the spinal cord to the PAG, tracer was injected in different parts of the PAG, and the number of retrogradely labeled neurons were counted for each spinal segment. Results show that large segmental differences exist in the number of PAG projecting neurons throughout the length of the spinal cord and that different parts of the spinal cord project to specific areas in the PAG.

Spatiotemporal activation of lumbosacral motoneurons in the locomotor step cycle

The aim of this study was to produce a dynamic model of the spatiotemporal activation of ensembles of alpha motoneurons (MNs) in the cat lumbosacral spinal cord during the locomotor step cycle. The coordinates of MNs of 27 hindlimb muscles of the cat were digitized from transverse sections of spinal cord spanning the entire lumbosacral enlargement from the caudal part of L-4 to the rostral part of S-1 segments. Outlines of the spinal cord gray matter were also digitized. Models of the spinal cord were generated from these digitized data and displayed on a computer screen as three-dimensional (3-D) images. We compiled a chart of electromyographic (EMG) profiles of the same 27 muscles during the cat step cycle from previous studies and used these to modulate the number of active MNs in the 3-D images. The step cycle was divided into 100 equal intervals corresponding to about 7 ms each for gait of moderate speed. For each of these 100 intervals, the level of EMG of each muscle was used to scale the number of dots displayed randomly within the volume of the corresponding MN pool in the digital model. One hundred images of the spinal cord were thereby generated, and these could be played in sequence as a continuous-loop movie representing rhythmical stepping. A rostrocaudal oscillation of activity in hindlimb MN pools emerged. This was confirmed by computing the locus of the center of activation of the MNs in the 100 consecutive frames of the movie. The caudal third of the lumbosacral enlargement showed intense MN activity during the stance phase of locomotion. During the swing phase, the focus of activation shifted abruptly to the rostral part of the enlargement. At the stance-swing transition, a transient focus of activity formed in the most caudal part of the lumbosacral enlargement. This was associated with activation of gracilis, posterior biceps, posterior semimembranosus, and semitendinosus muscles. These muscles move the foot back and up to clear the ground during locomotion, a role that could be described as retraction. The spatiotemporal distribution of neuronal activity in the spinal cord during normal locomotion with descending control and sensory inputs intact has not been visualized before. The model can be used in the future to characterize spatiotemporal activity of spinal MNs in the absence of descending and sensory inputs and to compare these to spatiotemporal patterns in spinal MNs in normal locomotion