Sten Grillner

On the central generation of locomotion in the low spinal cat

SummaryA central network of neurones in the spinal cord has been shown to produce a rhythmic motor output similar to locomotion after suppression of all afferent inflow. The experiments were performed mainly in acute spinal cats (th. 12), which had received DOPA i.v. and the monoamine oxidase inhibitor Nialamide. In some preparations all dorsal roots supplying the spinal cord were transected, in others phasic afferent activity was suppressed by curarization. The activity was recorded as neurograms from nerve filaments or as electromyograms.It is concluded that:1.alternating activity between flexors and extensors of foot, ankle, knee, and hip of one limb can still occur2.the duration of the flexor discharges vary less with the cycle duration than the extensor discharges3.different flexor muscles may retain individual patterns4.the activity at different joints can be dissociated5.there is at least one network for each limb6.the coordination between the two hindlimbs can be alternating as in walking or be more closely spaced as in galloping7.alternating activity in the ankle remains even when only segments L6, L7 and S1 are intact.

THE MOTOR INFRASTRUCTURE: FROM ION CHANNELS TO NEURONAL NETWORKS

The vertebrate motor system is equipped with a number of neuronal networks that underlie different patterns of behaviour, from simple protective reflexes to complex movements. The current challenge is to understand the intrinsic function of these networks: that is, the cellular basis of motor behaviour. In one vertebrate model system, the lamprey, it has been possible to make the connection between different subtypes of ion channels and transmitters and their roles at the cellular and network levels. It is therefore possible to link the role of certain genes or molecules to motor behaviour in this system.

Biological Pattern Generation: The Cellular and Computational Logic of Networks in Motion

In 1900, Ramón y Cajal advanced the neuron doctrine, defining the neuron as the fundamental signaling unit of the nervous system. Over a century later, neurobiologists address the circuit doctrine: the logic of the core units of neuronal circuitry that control animal behavior. These are circuits that can be called into action for perceptual, conceptual, and motor tasks, and we now need to understand whether there are coherent and overriding principles that govern the design and function of these modules. The discovery of central motor programs has provided crucial insight into the logic of one prototypic set of neural circuits: those that generate motor patterns. In this review, I discuss the mode of operation of these pattern generator networks and consider the neural mechanisms through which they are selected and activated. In addition, I will outline the utility of computational models in analysis of the dynamic actions of these motor networks.

On the initiation of the swing phase of locomotion in chronic spinal cats.

In chronic spinal cats walking with the hind legs on a treadmill, one limb can be stopped by holding the paw while the other limb continues to walk. If the held limb is slowly brought backwards at one point the limb flexes and continues walking. It was found that the hip position at which the leg lifts off during such reaction is very close to the hip angle at the initiation of swing during locomotion. Similar findings were obtained by extending only the femur. The hand-held limb tends to initiate lift-off during the midstance or the midswing of the contralateral limb step cycle. It is concluded that hip position and the contralateral step cycle phase are two important factors determining the initiation of swing in one leg.

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.

Mechanisms for selection of basic motor programs - roles for the striatum and pallidum

The nervous system contains a toolbox of motor programs in the brainstem and spinal cord--that is, neuronal networks designed to handle the basic motor repertoire required for survival, including locomotion, posture, eye movements, breathing, chewing, swallowing and expression of emotions. The neural mechanisms responsible for selecting which motor program should be recruited at a given instant are the focus of this review. Motor programs are kept under tonic inhibition by GABAergic pallidal neurons (the output nuclei of the basal ganglia). The motor programs can be relieved from pallidal inhibition through activation of striatal neurons at the input stage of the basal ganglia. It is argued that the striatum has a prominent role in selecting which motor program should be called into action.

Excitatory amino acids and synaptic transmission: the evidence for a physiological function

For 30 years physiological techniques have been used to investigate excitatory amino acids as neurotransmitters. In the last ten years progress on the definition of receptor subtypes and the availability of more selective agonists and antagonists has fuelled physiological, neurochemical and histochemical approaches to elucidating the involvement of excitatory amino acids at synaptic sites throughout the vertebrate CNS. Here Max Headley and Sten Grillner assess the advances made in defining the roles of excitatory amino acids as functional transmitters, taking examples mainly from studies on the spinal cord, and comment on the limitations of the types of approach that are used in such studies.

Measured motion: searching for simplicity in spinal locomotor networks.

Spinal interneurons are organized into networks that control the activity and output of the motor system. This review outlines recent progress in defining the rules that govern the assembly and function of spinal motor networks, focusing on three main areas. We first examine how subtle variations in the wiring diagrams and organization of locomotor networks in different vertebrates permits animals to adapt their motor programs to the demands of their physical environment. We discuss how the membrane properties of spinal interneurons, and their synaptic interactions, underlie the modulation of motor circuits and encoded motor behaviors. We also describe recent molecular genetic approaches to map and manipulate the connectivity and interactions of spinal interneurons and to assess the impact of such perturbations on network function and motor behavior.

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.