Modulation of cellular mechanisms in a spinal locomotor network

Neuronal networks generate behaviour. Thus, to understand behaviour requires information on how neuronal networks work in terms of their cellular components. The overall aim of this work has been to link processes occurring at an ionic level to the operation of a neural network specialized for undulatory locomotion. To this end, we have combined physiological experiments with computational techniques in the analysis, using the lamprey spinal locomotor network as a model system.

The present study is focused on the importance of membrane properties for the operation of the spinal neural network working through reciprocal inhibition. In particular, the roles of low-voltage--activated (LVA) calcium currents and the different subtypes of calcium--dependent potassium (KCa) currents for the alternation between the left and right hemisegment are examined. The influence of KCa channels on the burst rate depends not only on which subtype of KCa that is modulated but also how and to what degree this network is activated. The spinal network can be activated by excitatory amino acids including, N-methyl-D aspartate (NMDA) which give rise to an alternating burst activity in a low-frequency range (0--3 Hz) whereas a burst range between 1-8 Hz is provided by an AMPA/kainate drive. A reduction of the conductance of the KCasub type, responsible for the spike frequency adaptation, could either decrease or increase the burst rate depending on the level of AMPA/kainate used to drive the network. Moreover, when the network is driven by NMDA the influence on the burst rate of this KCQ subtype decline as the NMDA drive increased as revealed both in experiments and computer simulations. A reduction of the conductance of the other KCa subtype instead increase the burst rate. Thus, one essential finding was the distinction between processes occurring with slow versus fast dynamics. This was found to apply both at a neuronal level, in the analysis of neuronal membrane potential oscillations, along with the network level, as revealed by the different roles of the two subtypes of KCa conductances on the burst rate.

This type of ion channel-cellular analysis is important as the operation of neural networks is affected by neuromodulators which target specific cellular mechanisms. Particularly GABA is described in the present work. We show that GABA could play a modulatory role in the regulation of the burst rate, the regularity of the burst pattern, and the intersegmental coordination between the spinal segments. The cellular mechanisms underlying the modulation of the network are also examined. Activation of GABA II receptors reduce the high--voltage-activated (HVA) calcium current and indirectly the KCa current (after hyperpolarization and frequency regulation), thus increasing the gain of the conversion from synaptic input to a train of action potentials. The tendency for post inhibitory rebound depolarization is also reduced due to a decreased LVA calcium current. By extending the neuronal simulation model with an LVA conductance we show that this will increase the reciprocal alternation rate on the network Ievel.