Peter Wallén

Neural networks that co-ordinate locomotion and body orientation in lamprey

The networks of the brainstem and spinal cord that co-ordinate locomotion and body orientation in lamprey are described. The cycle-to-cycle pattern generation of these networks is produced by interacting glutamatergic and glycinergic neurones, with NMDA receptor-channels playing an important role at lower rates of locomotion. The fine tuning of the networks produced by 5-HT, dopamine and GABA systems involves a modulation of Ca2+-dependent K+ channels, high- and low-threshold voltage-activated Ca2+ channels and presynaptic inhibitory mechanisms. Mathematical modelling has been used to explore the capacity of these biological networks. The vestibular control of the body orientation during swimming is exerted via reticulospinal neurones located in different reticular nuclei. These neurones become activated maximally at different angles of tilt.

Neural bases of goal-directed locomotion in vertebrates--an overview.

The different neural control systems involved in goal-directed vertebrate locomotion are reviewed. They include not only the central pattern generator networks in the spinal cord that generate the basic locomotor synergy and the brainstem command systems for locomotion but also the control systems for steering and control of body orientation (posture) and finally the neural structures responsible for determining which motor programs should be turned on in a given instant. The role of the basal ganglia is considered in this context. The review summarizes the available information from a general vertebrate perspective, but specific examples are often derived from the lamprey, which provides the most detailed information when considering cellular and network perspectives.

Intrinsic function of a neuronal network — a vertebrate central pattern generator

The cellular bases of vertebrate locomotor behaviour is reviewed using the lamprey as a model system. Forebrain and brainstem cell populations initiate locomotor activity via reticulospinal fibers activating a spinal network comprised of glutamatergic and glycinergic interneurons. The role of different subtypes of Ca2+ channels, Ca2+ dependent K+ channels and voltage dependent NMDA channels at the neuronal and network level is in focus as well as the effects of different metabotropic, aminergic and peptidergic modulators that target these ion channels. This is one of the few vertebrate networks that is understood at a cellular level.

A computer based model for realistic simulations of neural networks

The use of computer simulations as a neurophysiological tool creates new possibilities to understand complex systems and to test whether a given model can explain experimental findings. Simulations, however, require a detailed specification of the model, including the nerve cell action potential and synaptic transmission. We describe a neuron model of intermediate complexity, with a small number of compartments representing the soma and the dendritic tree, and equipped with Na+, K+, Ca2+, and Ca2+ dependent K+ channels. Conductance changes in the different compartments are used to model conventional excitatory and inhibitory synaptic interactions. Voltage dependent NMDA-receptor channels are also included, and influence both the electrical conductance and the inflow of Ca2+ ions. This neuron model has been designed for the analysis of neural networks and specifically for the simulation of the network generating locomotion in a simple vertebrate, the lamprey. By assigning experimentally established properties to the simulated cells and their synapses, it has been possible to verify the sufficiency of these properties to account for a number of experimental findings of the network in operation. The model is, however, sufficiently general to be useful for realistic simulation also of other neural systems.

Cellular bases of a vertebrate locomotor system – steering, intersegmental and segmental co-ordination and sensory control

The isolated brainstem-spinal cord of the lamprey is used as an experimental model in the analysis of the cellular bases of vertebrate locomotor behaviour. In this article we review the neural mechanisms involved in the control of steering, intersegmental co-ordination, as well as the segmental burst generation and the sensory contribution to motor pattern generation. Within these four components of the control system for locomotion, we now have good knowledge of not only the neurones that take part and their synaptic interactions, but also the membrane properties of these neurones, including ion channel subtypes, and their contribution to motor pattern generation.

Activation of NMDA receptors elecits fictive locomotion and bistable membrane properties in the lamprey spinal cord

The motor pattern underlying locomotion in the lamprey can be elicited in the spinal cord in vitro by applying excitatory amino acids that activate NMDA receptors. When this is done oscillatory membrane potentials phase-linked with the locomotory rhythm can be recorded in different types of neurones. In some spinal neurones large amplitude oscillation continues after elimination of synaptic input with application of TTX. This oscillatory pacemaker-like activity is dependent on an activation of NMDA receptors, and is probably important in the generation of locomotion.

The intrinsic function of a motor system — from ion channels to networks and behavior

The forebrain, brainstem and spinal cord contribution to the control of locomotion is reviewed in this article. The lamprey is used as an experimental model since it allows a detailed cellular analysis of the neuronal network underlying locomotion. The focus is on cellular mechanisms that are important for the pattern generation, as well as different types of pre- and postsynaptic modulation. This experimental model is bridging the gap between the molecular and cellular level to the network and behavioral level.

Transmitters, membrane properties and network circuitry in the control of locomotion in lamprey

Abstract The lamprey brainstem and spinal cord can be maintained in vitro . It is a simple vertebrate preparation with comparatively few neurones. The neural correlates of different patterns of behaviour can be elicited in this in-vitro preparation. The subject of this review is the neuronal organization underlying locomotion, and, in particular, the role of different types of interneurones and their transmitters and mode of synaptic interaction. Excitatory amino acids, glycine, GABA, 5-HT, tachykinins and CCK have been implied as putative transmitters. The activation of one type of excitatory amino acid receptor, the NMDA receptor, can elicit TTX-resistant pacemaker-like membrane, potential oscillations. 5-HT can exert indirectly a potentiating effect via a depression of the postspike after-hyperpolarization (Ca 2+ -dependent potassium channels).

Ion channels of importance for the locomotor pattern generation in the lamprey brainstem-spinal cord.

The intrinsic function of the spinal network that generates locomotion can be studied in the isolated brainstem‐spinal cord of the lamprey, a lower vertebrate. The motor pattern underlying locomotion can be elicited in the isolated spinal cord. The network consists of excitatory glutamatergic and inhibitory glycinergic interneurones with known connectivity. The current review addresses the different subtypes of ion channels that are present in the cell types that constitute the network. In particular the roles of the different subtypes of Ca2+ channels and potassium channels that regulate integrated neuronal functions, like frequency regulation, spike frequency adaptation and properties that are important for generating features of the motor pattern (e.g. burst termination), are reviewed. By knowing the role of an ion channel at the cellular level, we also, based on previous knowledge of network connectivity, can understand which effect a given ion channel may exert at the different levels from molecule and cell to network and behaviour.

The ionic mechanisms underlying N-methyl-d-aspartate receptor-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion

Activation of N-methyl-D-aspartate (NMDA) receptors can induce tetrodotoxin (TTX)-resistant membrane potential oscillations as well as fictive locomotion in the in vitro preparation of the lamprey spinal cord. The ionic basis of these oscillations were investigated in the presence of N-methyl-D,L-aspartate and TTX. Addition of blocking agents (2-amino-5-phosphonovalerate and tetraethylammonium (TEA)) and selective removal or substitution of certain ions (Mg2+, Ca2+, Na+, Ba2+) were used in the analysis of the oscillations. The depolarizing phase of the oscillation requires Na+ ions but not Ca2+ ions. The depolarization becomes larger if TEA is administered in the bath, which presumably is due to a blockade of potassium (K+) channels activated during the depolarizing phase. The repolarization appears to depend on a Ca2+ entry, which presumably acts indirectly by an activation of Ca2+-dependent K+ channels. Together with the NMDA-induced voltage dependence, this will bring the membrane potential back down to a hyperpolarized level.