Organization of mammalian locomotor rhythm and pattern generation

Abstract

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.

Fig. 1. Schematic representations of half-center CPG models

Circles represent spinal interneuron and diamonds represent motoneuron populations. Excitatory and inhibitory connections are shown by lines ending with arrow heads and small filled circles, respectively. A,B,C. Single-level half-centre models in which rhythm generation is produced by two excitatory interneuron populations (green stippled populations) interconnected by reciprocal inhibition (purple). The same interneurons excite the corresponding motoneuron populations as well as inhibitory interneurons responsible for rhythmic inhibition of motoneurons during locomotion. A. Classical half-center scheme. B. More complex patterns of motoneuron activity can be produced by connections from both half centers to some motoneuron populations (PBSt, posterior biceps semitendinosus). C. Motoneurons receive excitation during locomotion from interneurons with sensory input (hatched circles) as well the half-centres. D,E,F. Two-and three-level CPG architectures with separate rhythm generator (dark green circles) and pattern formation (light green) circuitry. E. As in C, a portion of motoneuron excitation during locomotion is mediated by interneurons with sensory input. There is reciprocal inhibition at both the rhythm generator and pattern formation levels. F. A three level CPG organization in which all locomotor excitation of motoneurons is mediated by interneurons with sensory input. See text for details.

Fig. 2. Rybak-McCrea CPG model

Detailed schematic of a computational model of the of the spinal circuitry with the two-level CPG. Rhythm Generator (RG) and Pattern Formation (PF) networks representing the two levels of the CPG are labelled on the right. The excitatory RG populations reciprocally inhibit each other via the inhibitory Inrg populations. The PF populations reciprocally inhibit each other through the Inpf inhibitory populations. The RG-E and RG-F populations have recurrent excitatory connections and excitatory connections between the half-centers. Locomotion is initiated by a tonic excitatory drive (MLR) to both the RG and PF populations. The locomotor rhythm and the durations of flexor and extensor phases are determined by the RG network which controls the activity of the PF network by a combination of direct excitation and inhibition mediated by the Inrg populations. PF population activity produces a phase-specific activation of the corresponding group of synergist motoneuron pools. Phase-dependent inhibition of motoneurons is produced by the Ia-E and Ia-F populations whose activity is regulated by excitation from the PF network and inhibition from Renshaw cells (R-E and R-F) as well as mutual inhibitory connections between the Ia populations. Afferent input from extensor muscle spindle (Ia) and tendon organ (Ib) afferents to the spinal circuits are shown on the left. Activity in Ia afferents evokes monosynaptic excitation of synergist (extensor) motoneurons and disynaptic inhibition of antagonists. During locomotion, extensor group Ia and Ib afferents access the CPG at the RG and PF levels through the Irg-E and Ipf-E populations, respectively. Extensor motoneurons also receive a phase-dependent excitation from the Iab-E population whose activity is augmented by group I sensory input during the extensor phase. The Iab-E population is inhibited at rest by tonic drive from the In-E population. This inhibition is removed during the extension phase by inhibition from the Inpf-F population. Further details in Rybak et al. (2006 a, .

Fig. 3. Sensory control of the CPG by extensor group I afferents

A1, B1, Simulations of the effects of stimulation of extensor group I afferents delivered during the flexion phase (A1) and the extension phase (B1). The top traces show the stimulus delivery (arbitrary units). The other traces show the average activity of RG and PF interneuron populations and flexor (Mn-F) and extensor (Mn-E) motoneurons (ordinate in spikes /s, abscissa in seconds). A2, B2. Rectified-integrated nerve recordings from decerebrate cats during MLR-evoked fictive locomotion. Vertical dashed lines indicate the step cycle period without sensory stimulation. In A2, a train of shocks (black rectangle) delivered to extensor group I afferents (lateral gastrocnemius nerve at 1.6 times threshold, T) during the flexion phase produced a premature onset of extension (rectified, integrated electroneurograms from knee extensors, quadriceps, and the ankle extensor, medial gastrocnemius) and terminated the ongoing flexion phase (see tibialis anterior activity). In A1 (and similar to A2) stimulation applied during flexion in the model also produced a short extensor burst followed by a shortened flexion phase. This “quick step” of activity was created by the increased activity at the PF level and inserted into the ongoing rhythm which did not change (see RG activities and arrows at the bottom). In B2 Stimulation of extensor group I afferents (plantaris, 1.6T) during the extension phase of fictive locomotion increased the size and duration of extensor motoneuron activity (anterior biceps and medial gastrocnemius) and shortened the duration of the following flexor phase (see sartorius activity). In B1 (and similar to B2) extensor phase group I stimulation increased PF-E population activity that enhanced and prolonged extensor motoneuron activity without changing the locomotor period (see equal length arrows at the bottom). From Rybak et al. (2006b).

Fig. 4. Extending the CPG to multiple motoneuron pools

A, In the unit burst generator (Grillner, 1981) interconnected half-centers generate the rhythm and control the activity of functional groups of motoneurons. B, Rhythm generation and pattern formation are separated in this architecture with a single RG and multiple, unit pattern formation modules.