Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion (original) (raw)
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Locomotor circuits in the mammalian spinal cord
Annual Review of Neuroscience, 2006
Intrinsic spinal networks, known as central pattern generators (CPGs), control the timing and pattern of the muscle activity underlying locomotion in mammals. This review discusses new advances in understanding the mammalian CPGs with a focus on experiments that address the overall network structure as well as the identification of CPG neurons. I address the identification of excitatory CPG neurons and their role in rhythm generation, the organization of flexor-extensor networks, and the diverse role of commissural interneurons in coordinating left-right movements. Molecular and genetic approaches that have the potential to elucidate the function of populations of CPG interneurons are also discussed.
eNeuro, 2015
The organization of neural circuits that form the locomotor central pattern generator (CPG) and provide flexor-extensor and left-right coordination of neuronal activity remains largely unknown. However, significant progress has been made in the molecular/genetic identification of several types of spinal interneurons, including V0 (V0D and V0V subtypes), V1, V2a, V2b, V3, and Shox2, among others. The possible functional roles of these interneurons can be suggested from changes in the locomotor pattern generated in mutant mice lacking particular neuron types. Computational modeling of spinal circuits may complement these studies by bringing together data from different experimental studies and proposing the possible connectivity of these interneurons that may define rhythm generation, flexor-extensor interactions on each side of the cord, and commissural interactions between left and right circuits. This review focuses on the analysis of potential architectures of spinal circuits that...
The Journal of Physiology, 2012
G. Zhong and others J Physiol 590.19 interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the organization of spinal locomotor networks.
Journal of Neurophysiology, 2017
Mapping the expression of transcription factors in the mouse spinal cord has identified ten progenitor domains, four of which are cardinal classes of molecularly defined, ventrally located interneurons that are integrated in the locomotor circuitry. This review focuses on the properties of these interneuronal populations and their contribution to hindlimb locomotor central pattern generation. Interneuronal populations are categorized based on their excitatory or inhibitory functions and their axonal projections as predictors of their role in locomotor rhythm generation and coordination. The synaptic connectivity and functions of these interneurons in the locomotor central pattern generators (CPGs) have been assessed by correlating their activity patterns with motor output responses to rhythmogenic neurochemicals and sensory and descending fibers stimulations as well as analyzing kinematic gait patterns in adult mice. The observed complex organization of interneurons in the locomotor...
Deciphering the organization and modulation of spinal locomotor central pattern generators
Journal of Experimental Biology, 2006
SUMMARY Networks within our spinal cord generate the basic pattern underlying walking. Over the past decade, much progress has been made in our understanding of their function in a variety of vertebrate species. A significant hurdle has been the identification of candidate populations of neurons that are involved in pattern generation in the spinal cord. Recently,systems neuroscientists in collaboration with molecular biologists have begun to dissect the circuitry underlying spinal locomotor networks. These advances have combined genetic and electrophysiological techniques using in vitro preparations of the mouse spinal cord. This review will discuss new advances in the field of spinal locomotor networks with emphasis on the mouse. Many of the behaviors fundamental to animal life, such as breathing,chewing and locomotion, are rhythmic activities controlled by neuronal networks. Discerning which neurons are members of these networks, their synaptic connectivity and their individual e...
Journal of Neurophysiology, 2000
Lesion studies have shown that neuronal networks in the ventromedial regions of the neonatal rat spinal cord are critical for the production of locomotion. We examined whether the locomotor cycle could be accurately predicted based on the activity recorded in a population of spinal interneurons located in these regions during pharmacologically induced locomotion. We used a Bayesian probabilistic reconstruction procedure to predict the most likely phase of locomotion given the observed activity in the neuronal population. The population reconstruction was able to predict the correct locomotor phase with high accuracy using a relatively small number of neurons. This result demonstrates that although the spike activity of individual spinal interneurons in the ventromedial region is weak and varies from cycle to cycle, the locomotor phase can be accurately predicted when information from the population is combined. This result is consistent with the proposed involvement of interneurons ...
Organization of mammalian locomotor rhythm and pattern generation
Brain Research Reviews, 2008
Central pattern generators (CPGs) located in the spinal cord produce the coordinated activation of flexor and extensor motoneurons during locomotion. Previously proposed architectures for the spinal locomotor CPG have included the classical half-center oscillator and the unit burst generator (UBG) comprised of multiple coupled oscillators. We have recently proposed another organization in which a two-level CPG has a common rhythm generator (RG) that controls the operation of the pattern formation (PF) circuitry responsible for motoneuron activation. These architectures are discussed in relation to recent data obtained during fictive locomotion in the decerebrate cat. The data show that the CPG can maintain the period and phase of locomotor oscillations both during spontaneous deletions of motoneuron activity and during sensory stimulation affecting motoneuron activity throughout the limb. The proposed two-level CPG organization has been investigated with a computational model which incorporates interactions between the CPG, spinal circuits and afferent inputs. The model includes interacting populations of spinal interneurons and motoneurons modeled in the Hodgkin-Huxley style. Our simulations demonstrate that a relatively simple CPG with separate RG and PF networks can realistically reproduce many experimental phenomena including spontaneous deletions of motoneuron activity and a variety of effects of afferent stimulation. The model suggests plausible explanations for a number of features of real CPG operation that would be difficult to explain in the framework of the classical single-level CPG organization. Some modeling predictions and directions for further studies of locomotor CPG organization are discussed.
Spinal interneurons providing input to the final common path during locomotion
Breathe, Walk and Chew: The Neural Challenge: Part I, 2010
As the nexus between the nervous system and the skeletomuscular system, motoneurons effect all behaviour. As such, motoneuron activity must be well-regulated so as to generate appropriately timed and graded muscular contractions. Accordingly, motoneurons receive a large number of both excitatory and inhibitory synaptic inputs from various peripheral and central sources. Many of these synaptic contacts arise from spinal interneurons, some of which belong to spinal networks responsible for the generation of locomotor activity. Although the complete definition of these networks remains elusive, it is known that the neural machinery necessary to generate the basic rhythm and pattern of locomotion is contained within the spinal cord. One approach to gaining insights into spinal locomotor networks is to describe those spinal interneurons that directly control the activity of motoneurons, so called "last-order" interneurons. In this review, we briefly survey the different populations of last-order interneurons that have been identified using anatomical, physiological, and genetic methodologies. We discuss the possible roles of these identified last-order interneurons in generating locomotor activity, and in the process, identify particular criteria that may be useful in identifying putative last-order interneurons belonging to spinal locomotor networks.
Delineating the Diversity of Spinal Interneurons in Locomotor Circuits
Locomotion is common to all animals and is essential for survival. Neural circuits located in the spinal cord have been shown to be necessary and sufficient for the generation and control of the basic locomotor rhythm by activating muscles on either side of the body in a specific sequence. Activity in these neural circuits determines the speed, gait pattern, and direction of movement, so the specific locomotor pattern generated relies on the diversity of the neurons within spinal locomotor circuits. Here, we review findings demonstrating that developmental genetics can be used to identify populations of neurons that comprise these circuits and focus on recent work indicating that many of these populations can be further subdivided into distinct subtypes, with each likely to play complementary functions during locomotion. Finally, we discuss data describing the manner in which these populations interact with each other to produce efficient, task-dependent locomotion.
Modeling the mammalian locomotor CPG: insights from mistakes and perturbations
Progress in brain research, 2007
A computational model of the mammalian spinal cord circuitry incorporating a two-level central pattern generator (CPG) with separate half-center rhythm generator (RG) and pattern formation (PF) networks is reviewed. The model consists of interacting populations of interneurons and motoneurons described in the Hodgkin-Huxley style. Locomotor rhythm generation is based on a combination of intrinsic (persistent sodium current dependent) properties of excitatory RG neurons and reciprocal inhibition between the two half-centers comprising the RG. The two-level architecture of the CPG was suggested from an analysis of deletions (spontaneous omissions of activity) and the effects of afferent stimulation on the locomotor pattern and rhythm observed during fictive locomotion in the cat. The RG controls the activity of the PF network that in turn defines the rhythmic pattern of motoneuron activity. The model produces realistic firing patterns of two antagonist motoneuron populations and gener...