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J F Wedderburn

Publications and source records attributed to J F Wedderburn.

10 recordsLinked to original sources
PubMed1995

Involvement of brainstem serotonergic interneurons in the development of a vertebrate spinal locomotor circuit.

Brainstem neurons modulate the rhythmic output of spinal locomotor circuitry in adult vertebrates, but how these influences develop is largely unknown. We demonstrate that the ingrowth of serotonergic axons to the spinal cord of Xenopus tadpoles plays a critical role in locomotor burst development by transforming the output of embryonic amphibian swimming circuitry into a more mature and flexible form. Our experiments show that exposure to a monoamine neurotoxin (5,7 dihydroxytryptamine) deletes serotonergic raphespinal projections and prevents the normal maturation of larval swimming. Furthermore, the mature larval rhythm resumes an embryo-like form following either a pharmacological blockade of serotonin receptors or when receptor activation is prevented by acute spinalization.

5,7-Dihydroxytryptamine↗
PubMed1994

Modulation of rhythmic swimming activity in post-embryonic Xenopus laevis tadpoles by 5-hydroxytryptamine acting at 5HT1a receptors.

5HT modulates the rhythmic locomotor output of most vertebrates by enhancing the duration and intensity of motor bursts in each cycle, but there is little clear evidence on the pharmacological profile of the 5HT receptor subtype(s) involved. In this study we extend our previous work on the role of 5HT in the development and modulation of locomotor behaviour in newly hatched Xenopus tadpoles by examining the 5HT receptor type responsible for enhancing the swimming activity in immobilized preparations. By applying a range of agonists and antagonists against different 5HT receptor subtypes, we conclude that serotonergic modulation of swimming activity is accomplished via the activation of just one receptor type with a pharmacological profile similar to the mammalian 5HT1a receptor. The effects of 5HT on burst duration (an increase) and on episode length (a decrease) are mimicked by the 5HT1a receptor agonists, 5-carboxamidotryptamine (5CT) and R(+)-8-OH-DPAT, and reversed by the 5HT1a receptor antagonist NAN-190. Agents acting at other 5HT1, as well as 5HT2 and 5HT3, receptor subtypes were without noticeable effect on the 5HT-enhanced swimming rhythm.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1994

Descending serotonergic spinal projections and modulation of locomotor rhythmicity in Rana temporaria embryos.

The neuroanatomy of descending spinal projections from serotonergic raphe interneurons in embryos of the amphibian, Rana temporaria, has been examined around the time of hatching by using immunocytochemical techniques. The results illustrate that at this early stage in development the ventrolateral spinal cord is richly innervated by 5HT immunoreactive (5HTi) raphe spinal axons and associated growth cones. Other regions are devoid of processes. In conjunction, the effects of bath applied 5-hydroxytryptamine (5HT, serotonin) and its metabolic precursor, 5-hydroxytryptophan (5HTP) on locomotor activity, was also investigated by monitoring ventral root activity during fictive swimming in immobilized animals. Fictive swimming activity is similarly modulated by both exogenously applied 5HT and enhanced endogenous release of 5HT (using 5HTP). These agents increase the duration and intensity of ventral root burst, decrease cycle frequency, lengthen rostrocaudal phase delays and reduce swimming episode duration. We conclude that by the time of hatching in Rana temporaria a functional endogenous serotonergic system is established in the spinal cord which modulates the output of the central pattern generator for swimming. We compare and contrast these results with homologous descending pathways in other vertebrates, especially in a related amphibian Xenopus laevis at equivalent stages in development.

Animals↗
PubMed1992

Modulation of swimming rhythmicity by 5-hydroxytryptamine during post-embryonic development in Xenopus laevis.

During the first 24 h of post-embryonic development in Xenopus laevis, a rapid change in the neural activity underlying swimming occurs in which the duration of ventral root discharge on each cycle increases from a single compound impulse to discrete bursts of activity. Moreover, this change in motor output progresses rostrocaudally, suggesting that it could result from the influence of a descending neural pathway upon the spinal rhythm-generating circuitry during early post-embryonic development. To begin to examine whether serotonergic neurons of brainstem raphe nuclei might have a role in this swimming development, we have studied the effects of 5-hydroxytryptamine (5HT) on fictive swimming in embryonic and larval animals. As previously demonstrated for other vertebrate locomotor rhythms, we find that bath-applied 5HT enhances the duration of motor activity on each cycle of larval fictive swimming. In addition, our results show that the sensitivity of the swimming rhythm to exogenous 5HT follows a strict rostrocaudal gradient. In young embryos (stages 32-36) 5HT does not affect the duration of ventral root impulses per cycle; by the time of hatching (stage 37/38), rostral but not caudal discharge is enhanced, and by stage 42 (24 h post-hatching) 5HT can increase motor burst durations along most of the length of the animal. These reversible changes induced by bath-applied 5HT closely resemble the normal rostrocaudal development of burst discharge during swimming in animals some 12 h older.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The post-embryonic development of cell properties and synaptic drive underlying locomotor rhythm generation in Xenopus larvae.

In the first 24 h of post-embryonic development, the motor rhythm underlying swimming in Xenopus laevis tadpoles changes from brief (ca. 7 ms) ventral root discharge in each cycle to bursts of activity lasting around 20 ms (Sillar et al. 1991). Because individual motoneurons in the spinal cord of newly hatched embryos normally fire only a single impulse per cycle, two possible changes underly the transition to motor bursts seen in larval ventral roots; desynchronization of neurons in a given ventral root which continue to fire once per cycle, or the developmental acquisition of a multiple spike capability in individual motoneurons. Here we have recorded intracellularly from ventrally positioned spinal neurons, presumed to be myotomal motoneurons, in stage 37/38 embryos and 24 h later in development in stage 42 larvae. We find that (i) larval neurons are able to fire more than one impulse per cycle of fictive swimming activity; (ii) unlike in the embryo, they generally will fire multiple impulses in response to injected depolarizing current; (iii) the synaptic drive to motoneurons during swimming increases dramatically in complexity, although it still consists of alternating phases of synaptic excitation and chloride-dependent inhibition, superimposed upon tonic synaptic depolarization. The results therefore suggest a developmental change in the membrane properties of rhythmically active neurons as a major factor in the post-embryonic development of swimming in Xenopus larvae. This change appears to occur in premotor rhythm generating interneurons as well as in the motoneurons themselves and may satisfy a demand for behavioural flexibility that allows larvae to survive in a complex and changing environment.

Animals↗
PubMed1991

The development of swimming rhythmicity in post-embryonic Xenopus laevis.

The post-embryonic development of 'fictive' swimming in immobilized Xenopus laevis tadpoles has been examined during the first day of larval life. In Xenopus embryos (stage 37-38; Nieuwkoop & Faber 1956), the rhythmic ventral root activity underlying swimming occurs as single brief (ca. 7 ms) compound impulses on each cycle. However, by stage 42 (about 24 h after hatching), ventral root discharge consists of bursts lasting around 20 ms per cycle. In addition to increased burst duration in each cycle of larval swimming, the range of cycle periods within an episode increases, although mean period values (ca. 70-80 ms) remain similar to those of the younger animal. Consequently, motoneurons at developmental stage 42 are active during swimming for a greater percentage (ca. 25%) of cycle time than at stage 37-38 (ca. 10%). Developmental stage 40 (ca. 12 h post-hatching) is an intermediate stage in rhythm development. Ventral root discharge varies from bursts of 10-20 ms at the start of an episode to embryonic (ca. 7 ms) spikes at the end of an episode. Furthermore, discharge varies from bursts of activity in rostral segments of stage 40 larvae to 7 ms spikes more caudally, as in embryos. The data thus suggest that Xenopus swimming rhythmicity develops relatively rapidly, along a rostrocaudal gradient, and may involve acquisition of multiple spiking in spinal neurons.

Animals↗