Modelling spinal circuitry involved in locomotor pattern generation: insights from deletions during fictive locomotion

Abstract

The mammalian spinal cord contains a locomotor central pattern generator (CPG) that can produce alternating rhythmic activity of flexor and extensor motoneurones in the absence of rhythmic input and proprioceptive feedback. During such fictive locomotor activity in decerebrate cats, spontaneous omissions of activity occur simultaneously in multiple agonist motoneurone pools for a number of cycles. During these 'deletions', antagonist motoneurone pools usually become tonically active but may also continue to be rhythmic. The rhythmic activity that re-emerges following a deletion is often not phase shifted. This suggests that some neuronal mechanism can maintain the locomotor period when motoneurone activity fails. To account for these observations, a simplified computational model of the spinal circuitry has been developed in which the locomotor CPG consists of two levels: a half-centre rhythm generator (RG) and a pattern formation (PF) network, with reciprocal inhibitory interactions between antagonist neural populations at each level. The model represents a network of interacting neural populations with single interneurones and motoneurones described in the Hodgkin-Huxley style. The model reproduces the range of locomotor periods and phase durations observed during real locomotion in adult cats and permits independent control of the level of motoneurone activity and of step cycle timing. By altering the excitability of neural populations within the PF network, the model can reproduce deletions in which motoneurone activity fails but the phase of locomotor oscillations is maintained. The model also suggests criteria for the functional identification of spinal interneurones involved in the mammalian locomotor pattern generation.

Organization of mammalian locomotor rhythm and pattern generation

“…A similar conclusion about separation of rhythm and motoneuron activation duties arose from intracellular studies of deletions of scratch reflex activity in the turtle (Robertson and Stein, 1988). Our observations on deletions and on the ability of sensory stimulation to alter phase switching within the ongoing step cycle without changing the phase of the post stimulation rhythm (e.g., Guertin et al, 1995;Perreault et al, 1995;Stecina et al, 2005) led to the proposal for a two-level CPG (Lafreniere-Roula and McCrea, 2005;Rybak et al, 2006a). It was recently suggested that a single-level CPG could produce non-resetting deletions if there were a powerful control mechanism that could regulate synaptic transmission between excitatory CPG interneurons and motoneurons (Kiehn, 2006).…”

“…when inhibition is blocked. We suggest that the flexor-extensor synchrony that follows the suppression of inhibition results from excitatory interconnections between the half-centers (Rybak et al, 2006a). Such connections might be analogous to those between excitatory CPG neurons in the lamprey (see Cangiano and Grillner, 2005).…”

“…Alternating bursting activity in the PF network follows that in the RG and produces phasic excitation of the corresponding motoneuron pools. The full description of the model can be found in Rybak et al (2006a).An important feature of the model is the ability to differentially regulate locomotor speed at the RG level and the level of motoneuron activity at the PF level. By changing MLR drive to the RG half-centers, locomotor phase durations and step cycle periods can be independently regulated (see Rybak et al, 2006a;McCrea and Rybak, 2007) over ranges that encompass those occurring during fictive locomotion in decerebrate cats (Yakovenko et al, 2005) and during treadmill locomotion in intact cats (e.g., Halbertsma, 1983).…”

“…Like earlier half-center models, our model relies on mutual inhibitory interconnections between half-centers to generate the alternating locomotor pattern. This reciprocal inhibition defines the termination of flexor and extensor bursts and an increase in this inhibition prolongs step cycle period (i.e., slows down the locomotor rhythm) (Rybak et al 2006a). Similar to experimental findings (see above) blocking inhibition in the model switches its operation to generating synchronous flexor and extensor bursts (Rybak et al 2006a).…”

Strategies for delineating spinal locomotor rhythm-generating networks and the possible role of Hb9 interneurones in rhythmogenesis

“…While McCrea and colleagues present some compelling evidence in support of a two-layer model, their evidence that the rhythm-generating layer is organised as half-centres is much less convincing. These investigators rely on spontaneous (Lafreniere-Roula and McCrea, 2005;Rybak et al, 2006a) or evoked (Rybak et al, 2006b) "deletions" of activity in single motor nerves that either are ("resetting" deletions) or are not ("non-resetting" deletions) associated with disruptions of rhythm. They reason that since these non-resetting deletions can be seen in either flexor or extensor muscle nerves, the rhythm-generating layer must excite both the flexor and extensor pattern formation half-centres.…”