Faculty Opinions recommendation of Basis of changes in left-right coordination of rhythmic motor activity during development in the rat spinal cord.

Author(s):  
Keith Sillar
2004 ◽  
Vol 92 (1) ◽  
pp. 648-652 ◽  
Author(s):  
Kiyomi Nakayama ◽  
Hiroshi Nishimaru ◽  
Norio Kudo

Networks generating locomotor-like rhythmic motor activity are formed during the last week of the fetal period in the rat spinal cord. We investigated the coordinated rhythmic motor activity induced in transverse slice preparations of the lumbar spinal cord taken from fetal rats as early as embryonic day (E) 16.5. In slices as thin as 100 μm, bath-application of 5-hydroxytryptamine (5-HT) induced rhythmic [Ca2+]i elevations in motoneurons labeled with Calcium Green-1 dextran. The rhythmic [Ca2+]i elevations were similar in frequency to that in the intact lumbar spinal cord, although there was no temporal correlation between the activity in the left and right sides of 100-μm slices. Such rhythmic [Ca2+]i elevations were observed in the slices taken from all lumbar segments. Moreover, the rhythmic activity was abolished by simultaneous blockade of glutamate, glycine, and GABAA receptors, indicating that synaptic transmission mediated by these receptors is important for the generation of the rhythm in these slices. Synchronous rhythmic activity between the left-right sides was found in slices thicker than 200 μm taken from any segmental level of the lumbar spinal cord. In these preparations, commissural neurons were activated synchronously with ipsilateral motoneurons. These results indicate that the neuronal networks sufficient to generate coordinated rhythmic activity are contained in one-half of a single lumbar segment at E16.5. Such spinal cord slices are a promising experimental model to investigate the neuronal mechanisms and the development of rhythm generation in the spinal cord.


1995 ◽  
Vol 74 (3) ◽  
pp. 1109-1117 ◽  
Author(s):  
K. C. Cowley ◽  
B. J. Schmidt

1. The role of inhibitory amino acid transmission in the coordination and generation of rhythmic motor activity was examined with the use of an in vitro neonatal rat spinal cord preparation. Before adding gamma-aminobutyric acid (GABA) or glycine receptor agonists and antagonists, rhythmic motor activity was induced by bath application of acetylcholine (ACh), N-methyl-D,L-aspartate (NMA), or serotonin (5-HT) while monitoring bilateral ankle flexor and extensor electroneurograms (ENGs). The timing of rhythmic flexor and extensor discharge was consistent with that seen during overground locomotion in 27% of 84 bath applications of these substances (n = 65 preparations). 2. Subsequent addition of the GABAA receptor agonist muscimol, the GABAB receptor agonist baclofen, or glycine, abolished rhythmic activity in 95% of the tested applications. 3. GABAB receptor blockade did not disrupt alternating patterns of ENG discharge. However, addition of the GABAA receptor antagonist bicuculline, or the glycine receptor antagonist strychnine, transformed alternating flexor-extensor and left-right activity into patterns characterized by bilaterally synchronous rhythmic activation of all hindlimb ENGs. The onset of individual ENG bursts was more abrupt following bicuculline or strychnine. Strychnine also synchronized high-frequency (4-8 Hz) packets of rhythmic discharge within ENG bursts. 4. Some preparations developed synchronous, but unstable, rhythmic activity in the presence of bicuculline or strychnine alone. However, NMA, 5-HT, or ACh was usually required in addition to these antagonists to promote sustained rhythmic activity.(ABSTRACT TRUNCATED AT 250 WORDS)


1999 ◽  
Vol 82 (2) ◽  
pp. 741-746 ◽  
Author(s):  
Ole Kiehn ◽  
Keith T. Sillar ◽  
Ole Kjaerulff ◽  
Jonathan R. McDearmid

We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5–50 μM) elicited either no measurable root activity, or activity of a highly variable nature. When present, the NA-induced activity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony between antagonistic motor pools. Finally, in a few cases, NA induced a slow locomotor-like rhythm, in which activity alternated between the left and right sides, and between rostral and caudal roots on the same side. As shown previously, stable locomotor activity could be induced by bath application of N-methyl-d-aspartate (NMDA; 4–8.5 μM) and/or serotonin (5-HT; 4–20 μM). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1–5 μM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background activity of the ongoing rhythm. Moreover, NA did not obviously affect the left/right and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT locomotor rhythm sometimes displayed a time-dependent breakdown in coordination, ultimately resulting in tonic ventral root activity. However, the addition of NA to the NMDA/5-HT saline could reinstate a well-coordinated locomotor rhythm. We conclude that exogenously applied NA can elicit tonic activity or can trigger a slow, irregular and often synchronous motor pattern. When NA is applied during ongoing locomotor activity, the amine has a distinct slowing effect on the rhythm while preserving the normal coordination between flexors and extensors. The ability of NA to “rescue” rhythmic locomotor activity after its time-dependent deterioration suggests that the amine may be important in the maintenance of rhythmic motor activity.


2003 ◽  
Vol 89 (3) ◽  
pp. 1187-1195 ◽  
Author(s):  
Jun Ren ◽  
John J. Greer

Patterned spontaneous activity is generated in developing neuronal circuits throughout the CNS including the spinal cord. This activity is thought to be important for activity-dependent neuronal growth, synapse formation, and the establishment of neuronal networks. In this study, we examine the spatiotemporal distribution of motor patterns generated by rat spinal cord and medullary circuits from the time of initial axon outgrowth through to the inception of organized respiratory and locomotor rhythmogenesis during late gestation. This includes an analysis of the neuropharmacological control of spontaneous rhythms generated within the spinal cord at different developmental stages. In vitro spinal cord and medullary-spinal cord preparations isolated from rats at embryonic ages (E)13.5–E21.5 were studied. We found age-dependent changes in the spatiotemporal pattern, neurotransmitter control, and propensity for the generation of spontaneous rhythmic motor discharge during the prenatal period. The developmental profile of the neuropharmacological control of rhythmic bursting can be divided into three periods. At E13.5–E15.5, the spinal networks comprising cholinergic and glycinergic synaptic interconnections are capable of generating rhythmic activity, while GABAergic synapses play a role in supporting the spontaneous activity. At late stages (E18.5–E21.5), glutamate drive acting via non- N-methyl-d-aspartate (non-NMDA) receptors is primarily responsible for the rhythmic activity. During the middle stage (E16.5–E17.5), the spontaneous activity results from the combination of synaptic drive acting via non-NMDA glutamatergic, nicotinic acetylcholine, glycine, and GABAA receptors. The modulatory actions of chloride-mediated conductances shifts from predominantly excitatory to inhibitory late in gestation.


Author(s):  
V. Kriho ◽  
H.-Y. Yang ◽  
C.-M. Lue ◽  
N. Lieska ◽  
G. D. Pappas

Radial glia have been classically defined as those early glial cells that radially span their thin processes from the ventricular to the pial surfaces in the developing central nervous system. These radial glia constitute a transient cell population, disappearing, for the most part, by the end of the period of neuronal migration. Traditionally, it has been difficult to definitively identify these cells because the principal criteria available were morphologic only.Using immunofluorescence microscopy, we have previously defined a phenotype for radial glia in rat spinal cord based upon the sequential expression of vimentin, glial fibrillary acidic protein and an intermediate filament-associated protein, IFAP-70/280kD. We report here the application of another intermediate filament-associated protein, IFAP-300kD, originally identified in BHK-21 cells, to the immunofluorescence study of radial glia in the developing rat spinal cord.Results showed that IFAP-300kD appeared very early in rat spinal cord development. In fact by embryonic day 13, IFAP-300kD immunoreactivity was already at its peak and was observed in most of the radial glia which span the spinal cord from the ventricular to the subpial surfaces (Fig. 1). Interestingly, from this time, IFAP-300kD immunoreactivity diminished rapidly in a dorsal to ventral manner, so that by embryonic day 16 it was detectable only in the maturing macroglial cells in the marginal zone of the spinal cord and the dorsal median septum (Fig. 2). By birth, the spinal cord was essentially immuno-negative for this IFAP. Thus, IFAP-300kD appears to be another differentiation marker available for future studies of gliogenesis, especially for the early stages of radial glia differentiation.


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