Biomedical subjects

Nicholas Dale

Publications and source records attributed to Nicholas Dale.

21 records · Page 2Linked to original sources

PubMed2002

Spike-independent release of ATP from Xenopus spinal neurons evoked by activation of glutamate receptors.

As the release of ATP from neurons has only been directly studied in a few cases, we have used patch sniffing to examine ATP release from Xenopus spinal neurons. ATP release was detected following intracellular current injection to evoke spikes. However, spiking was not essential as both glutamate and NMDA could evoke release of ATP in the presence of TTX. Neither acetylcholine nor high K(+) was effective at inducing ATP release in the presence of TTX. Although Cd(2+) blocked glutamate-evoked release of ATP suggesting a dependence on Ca(2+) entry, neither omega-conotoxin-GVIA nor nifedipine prevented ATP release. N-type and L-type channels are thus not essential for glutamate-evoked ATP release. That glutamate receptors can elicit release in the absence of spiking suggests a close physical relationship between these receptors, the Ca(2+) channels and release sites. As the dependence of ATP release on the influx of Ca(2+) through Ca(2+) channel subtypes differs from that of synaptic transmitter release, ATP may be released from sites that are distinct from those of the principal transmitter. In addition to its role as a fast transmitter, ATP may thus be released as a consequence of the activation of excitatory glutamatergic synapses and act to signal information about activity patterns in the nervous system.

Adenosine Triphosphate↗

PubMed1991

The Isolation and Identification of Spinal Neurons That Control Movement in the Xenopus Embryo.

A procedure for isolating spinal neurons of the Xenopus embryo has been devised. Using a variety of methods four of the eight previously described categories of neuron can be distinguished in vitro. Firstly, since many anatomical features of the neurons survived dissociation, sensory neurons and glycinergic inhibitory interneurons could be identified after isolation using anatomical criteria. Secondly, by selective labelling of the neurons in the intact spinal cord with fluorescein-conjugated dextran amines prior to dissociation, three classes of isolated neuron could be identified: motoneurons, putative excitatory interneurons and, once again, inhibitory interneurons. The identity of the inhibitory interneurons has been confirmed using glycine immunocytochemistry. The physiological properties of the isolated neurons were similar to those of their in vivo counterparts. The dissociated neurons exhibited strong membrane accommodation and outward rectification, both of which could be blocked by the injection of Cs+ ions. The neurons also retained their receptors for the agonists N-methyl-d-aspartate, kainate, quisqualate, glycine and GABA. Both the membrane properties and pharmacological sensitivity of the isolated neurons therefore appeared to be unaltered by the dissociation procedure. Thus the four classes of neuron from the Xenopus embryonic nervous system that can be identified after isolation constitute the basis for a valid model for detailed study of how the properties of individual neurons contribute to the functioning of the circuitry that underlies locomotor pattern generation in vertebrates.

Journal Article↗

PubMedDate not supplied

Coordinated motor activity in simulated spinal networks emerges from simple biologically plausible rules of connectivity.

The spinal motor circuits of the Xenopus embryo have been simulated in a 400-neuron network. To explore the consequences of differing patterns of synaptic connectivity within the network for the generation of the motor rhythm, a system of biologically plausible rules was devised to control synapse formation by three parameters. Each neuron had an intrinsic probability of synapse formation (P(soma), specified by a space constant lambda) that was a monotonically decreasing function of its soma location in the rostro-caudal axis of the simulated network. The neurons had rostral and caudal going axons of specified length (L(axon)) associated with a probability of synapse formation (P(axon)). The final probability of synapse formation was the product of P(soma) and P(axon). Realistic coordinated activity only occurred when L(axon) and the probabilities of interconnection were sufficiently high. Increasing the values of the three network parameters reduced the burst duration, cycle period, and rostro-caudal delay and increased the reliability with which the network functioned as measured by the coefficient of variance of these parameters. Whereas both L(axon) and P(axon) had powerful and consistent effects on network output, the effects of lambda on burst duration and rostro-caudal delay were more variable and depended on the values of the other two parameters. This network model can reproduce the rostro-caudal coordination of swimming without using coupled oscillator theory. The changes in network connectivity and resulting changes in activity explored by the model mimic the development of the motor pattern for swimming in the real embryo.

Animals↗