strychnine and Magnesium-Deficiency

Rat spinal networks generate a spontaneous rhythmic output directed to motoneurons under conditions of increased excitation or of disinhibition. It is not known whether these differently induced rhythms are produced by a common rhythm generator. To investigate the generation and the propagation of rhythmic activity in spinal networks, recordings need to be made from many neurons simultaneously. Therefore extracellular multisite recording was performed in slice cultures of embryonic rat spinal cords grown on multielectrode arrays. In these organotypic cultures most of the spontaneous neural activity was nearly synchronized. Waves of activity spread from a source to most of the network within 35-85 ms and died out after a further 30-400 ms. Such activity waves induced the contraction of cocultured muscle fibres. Several activity waves could be grouped into aperiodic bursts. Disinhibition with bicuculline and strychnine or increased excitability with high K(+) or low Mg(2+) solutions could induce periodic bursting with bursts consisting of one or several activity waves. Whilst the duration and period of activity waves were similar for all protocols, the duration and period of bursts were longer during disinhibition than during increased excitation. The sources of bursting activity were mainly situated ventrally on both sides of the central fissure. The pathways of network recruitment from one source were variable between bursts, but they showed on average no systematic differences between the protocols. These spatiotemporal similarities under conditions of increased excitation and of disinhibition suggest a common spinal network for both types of rhythmic activity.

Topics: Action Potentials; Animals; Bicuculline; Biological Clocks; Electrophysiology; Fetus; GABA Antagonists; Glycine Agents; Locomotion; Magnesium Deficiency; Motor Neurons; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Nerve Net; Neural Inhibition; Neurons; Organ Culture Techniques; Periodicity; Potassium; Rats; Reaction Time; Spinal Cord; Strychnine

Locomotion in vertebrates is controlled by central pattern generators in the spinal cord. The roles of specific network architecture and neuronal properties in rhythm generation by such spinal networks are not fully understood. We have used multisite recording from dissociated cultures of embryonic rat spinal cord grown on multielectrode arrays to investigate the patterns of spontaneous activity in randomised spinal networks. We were able to induce similar patterns of rhythmic activity in dissociated cultures as in slice cultures, although not with the same reliability and not always with the same protocols. The most reliable rhythmic activity was induced when a partial disinhibition of the network was combined with an increase in neuronal excitability, suggesting that both recurrent synaptic excitation and neuronal excitability contribute to rhythmogenesis. During rhythmic activity, bursts started at several sites and propagated in variable ways. However, the predominant propagation patterns were independent of the protocol used to induce rhythmic activity. When synaptic transmission was blocked by CNQX, APV, strychnine and bicuculline, asynchronous low-rate activity persisted at approximately 50% of the electrodes and approximately 70% of the sites of burst initiation. Following the bursts, the activity in the interval was transiently suppressed below the level of intrinsic activity. The degree of suppression was proportional to the amount of activity in the preceding burst. From these findings we conclude that rhythmic activity in spinal cultures is controlled by the interplay of intrinsic neuronal activity and recurrent excitation in neuronal networks without the need for a specific architecture.

Topics: Action Potentials; Animals; Bicuculline; Biological Clocks; Cell Culture Techniques; Cells, Cultured; Electrophysiology; Excitatory Amino Acid Antagonists; Fetus; GABA Antagonists; GABA-A Receptor Antagonists; Glycine Agents; Locomotion; Magnesium Deficiency; Nerve Net; Neurons; Periodicity; Potassium; Rats; Receptors, GABA-A; Receptors, Glutamate; Receptors, Glycine; Spinal Cord; Strychnine; Synaptic Transmission

Topics: Adolescent; Adult; Animals; Apnea; Bradycardia; Child; Disease Models, Animal; Electrocardiography; Female; Humans; Infant; Infant, Newborn; Magnesium; Magnesium Deficiency; Male; Pregnancy; Rats; Respiratory System; Strychnine; Sudden Infant Death