Measured motion: searching for simplicity in spinal locomotor networks

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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.

Introduction

Because movement sets the tone for animal behavior, nervous systems need to devote a considerable fraction of their computational power to the job of activating muscles in precise temporal and spatial patterns that drive coordinated motor activity. Even the simplest of motor tasks, in the most primitive of animals, demands the integrated activity of a diverse set of neural circuits. In vertebrates, the planning of movement before overt muscle activity involves the recruitment of many supraspinal networks. But the executive element of motor control  the task of determining which muscles are to be activated, how intensely, and for how long  has been assigned to neural circuits located within the spinal cord.

At the core of the spinal motor system are sets of local interneurons which assemble themselves into ordered networks capable of controlling the activity and output of spinal motor neurons. These networks are usually referred to as central pattern generators (CPGs). While CPGs possess a high degree of autonomy in output, their activation depends on input from supraspinal command centers, notably those in the mesencephalon and caudal diencephalon. Sensory feedback pathways that report on the state of muscle activity have critical roles in refining the pattern of locomotor output in each movement cycle, permitting the core CPG network to adapt itself to the many obstacles and uncertainties that confront animals during their ambulatory excursions [1]. Defining the intrinsic logic of spinal CPG networks, and the way in which they integrate descending commands and sensory feedback information, remains one of the fundamental challenges in the broader field of motor systems neuroscience.

Over the past few decades, progress in clarifying principles of spinal motor control has benefited from a wide range of ideas and approaches  cellular neurophysiology and anatomy, consideration of the biomechanics of limb movement, as well as computational descriptions of simulated motor behavior (see [2, 3, 4••]). Building on this foundation, there has been a gradual broadening of interest in the organization and function of spinal motor systems, driven in part by advances in three additional areas. Biophysical studies have provided an increasingly quantitative account of the membrane, synaptic and integrative features of identified neurons within spinal motor networks, especially so in aquatic vertebrates [5, 6]. Molecular genetic strategies have progressed to the point that it is now feasible to manipulate identified spinal neurons with unprecedented specificity and to test the impact of such perturbations on circuit function and motor behavior [3, 7, 8]. There has also been an increasing interest in comparative aspects of spinal motor control  probing key differences in the organization of locomotor networks that permit animals to execute motor programs that are fitted to the specialized needs of their physical environment [9].

In this brief review, we set out to highlight some of the recent advances in these research areas, while pointing out the many puzzles and uncertainties that still confound the goal of arriving at a ‘simple’ set of rules that govern the organization and function of spinal motor networks.

Section snippets

From lamprey to mammals: evolving patterns of vertebrate motor coordination

The first vertebrates to emerge, some 500 millions year ago, are today represented by lampreys and hagfish, two phylogenetically distinct and conserved agnathan (jawless) groups that lack paired appendages. The lamprey locomotor network, arguably the ancestral doyen of vertebrate locomotor systems, generates a pronounced left–right alternation of motor output in each segment, while imposing a segmental phase lag that results in the propagation of an undulatory wave of motor activity along the

A physiological framework for spinal motor control networks

Evolutionary considerations aside, just how near are we to defining a canonical spinal circuit for vertebrate locomotion? And what has the advent of molecular genetic methods for spinal network analysis added to facts and principles gleaned from tried and true physiological approaches? We first discuss the physiological canon that provides the underpinnings of current views of the spinal locomotor network, and then assess the impact of molecular genetic approaches.

Like all circuits, spinal

Spinal interneuron subtypes: molecular diversity in search of functional correlates

Physiological and anatomical data that document the functional diversity of interneurons involved in regulating motor output have been augmented more recently by molecular descriptions of interneuron subtype, revealed most clearly by profiles of transcription factor expression [7, 63]. Interneurons that settle in the ventral spinal cord with presumed roles in the control of motor pattern derive from four progenitor populations, which give rise at cell cycle exit to four cardinal interneuron

Locomotor network properties tuned by slow synaptic actions

Although the core features of locomotor network organization reflect the circuitry and actions of interneurons that mediate fast synaptic responses, more refined aspects of circuit function and motor output are controlled by the influence of neuromodulators released during activation of the core locomotor network. These modulatory signaling systems elicit slower synaptic actions, usually through activation of G-protein-coupled receptors (GPCRs; Figure 5). Typically, GPCR activation regulates

What next in the measurement of motion?

The logic of neuronal networks and their link to physiological function, whether in the context of movement itself or other behaviors, is likely to emerge only when sufficiently detailed information is available on the identity and membrane properties of individual neuronal components of the network, the synaptic interactions that connect and coordinate these neurons, and the adaptive properties of these networks under different behavioral constraints. In the case of the spinal networks that

References and recommended reading

Papers of particular interest, published within the last two years, have been highlighted as:

  • •• of outstanding interest

Acknowledgements

We thank the Kavli Foundation for providing a venue that led to initial discussions on aspects of spinal motor control included in this review, and Abdel El Manira and Ole Kiehn for comments and suggestions. We are also grateful to Ira Schieren and Kathy MacArthur for help in preparing the figures and text. TMJ is supported by grants from ProjectALS and NINDS and is an investigator of the Howard Hughes Medical Institute. SG is supported by The Swedish Research Council (M; NT), the European

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