Fictive Locomotor Activity Research Articles

A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey.

1. To analyze the function of the spinal interneuronal network generating locomotion in the lamprey CNS, a vertebrate model system, we performed computer simulations with realistic model neurons possessing the essential properties of their biological counterparts. 2. The segmental network has been simulated by modeling experimentally established types of neurons with their specific membrane properties and synaptic interconnections. Fictive locomotor activity, which can be experimentally induced by elevating the background excitability by bath application of excitatory amino acids, was simulated by opening membrane conductances for kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. Kainate/AMPA receptor activation induced a rhythm in the middle and upper part of the physiological burst frequency range, whereas NMDA receptor activation evoked bursting in the lower part of the range, which corresponds well to earlier experimental findings. 3. Several factors contributing to the termination of the burst were studied and their interaction was assessed in simulations of the network. 1) The summation of spike afterhyperpolarizations (late AHPs), leading to adaptation of the discharge, acts as a primary burst-terminating factor at lower rates of kainate/AMPA-induced bursting, and it also interacts with the NMDA-induced oscillatory membrane properties during slow rhythmicity. 2) The termination of the depolarized NMDA plateau is another important factor during NMDA-evoked rhythmicity. 3) The synaptic inhibition from lateral interneurons to the interneurons mediating reciprocal inhibition is important at higher rates of kainate/AMPA-induced bursting. 4. The mechanism of action of 5-hydroxytryptamine (5-HT) on the lamprey segmental network was further investigated by simulation. 5-HT is known to lower the burst frequency during fictive locomotion and also to decrease the conductance through the Ca(2+)-dependent K+ channels, and thereby the size of the late AHP that follows the action potential. Decreasing this conductance in the network simulations resulted in a lesser amount of AHP summation and thereby less frequency adaptation during the burst, longer bursts, and a lower locomotor frequency. Thus the selective action of 5-HT on the Ca(2+)-dependent K+ channels, and hence on the AHP, can account for the modulatory effect on the fictive locomotor rhythm seen experimentally. 5. The results demonstrate that the present simulation of the segmental network can account for essential features of the motor pattern seen experimentally during lamprey locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of an NMDA-receptor antagonist, MK-801, on central locomotor programming in the rabbit

NMDA has been shown to disclose spinal fictive locomotor activity in various in vitro preparations. In the present work the NMDA-mediated effects of endogenously released excitatory aminoacids (EAA) on fictive locomotion in the adult rabbit preparation were assessed in vivo using systemic injections of a non competitive NMDA-antagonist, MK-801. In acute low spinal and curarized preparations, the amplitude of the "spontaneous" fictive locomotor activities recorded from hindlimb muscle nerves after nialamide-DOPA pretreatment was much decreased in flexor and extensor nerves after MK-801 administration (0.25 mg/kg i.v.) whereas the locomotor period increased slightly. The more potent locomotor bursts, evoked by repetitive sural nerve stimulation at 10 Hz during 10 s, were differently affected after MK-801: the main effect was a lengthening of the locomotor period and a less drastic drop in the burst amplitude. These changes in the burst period were maximal for activities evoked by A fibre group stimulation (+100%) and less when C fibres were recruited (+70%). In decerebrate curarized preparations where the locomotor sequences were evoked either by sural nerve stimulation or by stimulation of the mesencephalic locomotor region, MK-801 (0.25 mg/kg i.v.) caused the same drop in burst amplitude (by at least 50%) as in the spinal preparation but, in contrast, it reinforced rhythmic bursting: this was revealed by a clear shortening (up to -65%) of the locomotor period and by the prolongation of rhythmic bursting after stimulation. All these effects obtained in decerebrate preparations were maximal 20-30 min after MK-801 injection.(ABSTRACT TRUNCATED AT 250 WORDS)

N-methyl-D-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey

Bath application of N-methyl-aspartate induces fictive locomotor activity in the isolated spinal cord preparation of the lamprey, as well as TTX-resistant membrane potential oscillations in many individual neurons. This inherent oscillatory activity is shown to depend on a specific activation of N-methyl-D-aspartate (NMDA) receptors. This activation initiates voltage-dependent, magnesium-requiring membrane potential bistability, presumably due to a development of a region of negative slope conductance in the current-voltage relation of the neuron. When sodium ions were removed from the bathing solution, oscillations disappeared, and the membrane potential was maintained at a hyperpolarized level, suggesting that the depolarizing current during the oscillatory cycle is mainly carried by sodium ions. Replacing Ca2+ with Ba2+ also leads to a cessation of oscillatory activity, with the membrane potential remaining at the more depolarized level. This indicates an involvement of a Ca2+-dependent K+ current during the repolarization phase. These findings, together with the voltage dependence, can account for the main characteristics of the NMDA receptor-induced, TTX-resistant membrane potential oscillations. This oscillatory behavior has been demonstrated in motoneurons and in several interneurons including CC interneurons but has not been found in edge cells, dorsal cells, or lateral interneurons. The possibility that inherent oscillatory membrane properties may contribute to the activity pattern during fictive locomotion was investigated in experiments with intracellular current injection in the absence of TTX. The stimulation effects obtained required the presence of magnesium ions and were analogous to the stimulation effects seen during oscillations after TTX blockade. Together with similarities in, for instance, frequency and amplitude between the locomotor oscillatory activity and the TTX-resistant oscillations, the results are compatible with an involvement of inherent, oscillatory membrane properties during fictive locomotion in the lamprey spinal cord.

Müller cells and other reticulospinal neurones are phasically active during fictive locomotion in the isolated nervous system of the lamprey

Reticulospinal neurones were studied during fictive locomotion in the lamprey brainstem-spinal cord in vitro preparation. Intracellular recordings were made from the large reticulospinal Müller cells located in the mesencephalon (M 1–3), rostral (I 1) and middle (B 1–5) rhombencephalon, the Mauthner cells, and the V cells located within the posterior reticular nucleus during fictive locomotor activity. All cells were depolarized during motor activity on either the ipsilateral (M 1–3, I 1, B 1–5 and V cells) or the contralateral (Mauthner cell (crossed axon)) side. During locomotor activity and long-lasting burst activity, phasic membrane potential oscillations occurred well correlated to the ventral root activity.

Peripheral control of the cat's step cycle. I. Phase dependent effects of ramp-movements of the hip during "fictive locomotion".

Acute spinal and curarized cats can generate "fictive locomotor activity" after an i.v. injection of Nialamid followed by 4-AP and L-DOPA. The efferent burst activity to flexors and extensors can be recorded in peripheral nerve filaments. Ramp-formed movements were applied in the hip at constant angular velocity in different phases of the spontaneous efferent burst activity. The cycle duration was markedly influenced. A flexion or an extension ramp applied in the early part of the "step-cycle" (during flexor activity) will prolong the cycle duration, but in the later part of the cycle instead a marked shortening effect will occur. The transition from a prolongation to a shortening is very steep for the extensive-ramps, with a subsequent gradual increase from a shortening to a lengthening of the cycle. This type of phase response curve expresses a potent peripheral modulatory effect on the central pattern generator. A ramp movement (flexion or extension) applied in the beginning of the flexor burst will reinforce the flexor activity. In the end of the flexor burst instead there is a directional sensitivity with positive feedback, resulting in an excitation of the flexor activity for flexion ramps, but a depression of the flexor activity for extension-ramps. Extension-ramps also show a position dependent effect which enhances the response in the flexors for more extended hip positions.