Patterns of presynaptic activity and synaptic strength interact to produce motor output.

Motor neuron activity is coordinated by premotor networks into a functional motor pattern by complex patterns of synaptic drive. These patterns combine both the temporal pattern of spikes of the premotor network and the profiles of synaptic strengths (i.e., conductances). Given the complexity of premotor networks in vertebrates, it has been difficult to ascertain the relative contributions of temporal patterns and synaptic strength profiles to the motor patterns observed in these animals. Here, we use the leech (Hirudo sp.) heartbeat central pattern generator (CPG), in which we can measure both the temporal pattern and the synaptic strength profiles of the entire premotor network and the motor outflow in individual animals. In this system, a series of motor neurons all receive input from the same premotor interneurons of the CPG but must be coordinated differentially to produce a functional pattern. These properties allow a theoretical and experimental dissection of the rules that govern how temporal patterns and synaptic strength profiles are combined in motor neurons so that functional motor patterns emerge, including an analysis of the impact of animal-to-animal variation in input to such variation in output. In the leech, segmental heart motor neurons are coordinated alternately in a synchronous and peristaltic pattern. We show that synchronous motor patterns result from a nearly synchronous premotor temporal pattern produced by the leech heartbeat CPG. For peristaltic motor patterns, the staggered premotor temporal pattern determines the phase range over which segmental motor neurons can fire while synaptic strength profiles define the intersegmental motor phase progression realized.

Constancy and variability in the output of a central pattern generator.

Experimental and corresponding modeling studies have demonstrated a twofold to fivefold variation of intrinsic and synaptic parameters across animals, whereas functional output is maintained. These studies have led to the hypothesis that correlated, compensatory changes in particular parameters can at least partially explain the biological variability in parameters. Using the leech heartbeat central pattern generator (CPG), we selected three different segmental motor neurons that fire in a functional phase progression but receive input from the same four premotor interneurons. Previous work suggested that the phase progression arises because the pattern of relative strength of the four inputs varies systematically across the segmental motor neurons. Nevertheless, there was considerable animal-to-animal variation in the absolute strengths of these connections. We tested the hypothesis that functional output is maintained in the face of variation in the absolute strength of connections because relative strengths onto particular motor neurons are maintained. We found that relative strength is not strictly maintained across animals even as functional output is maintained, and animal-to-animal variations in relative strength of particular inputs do not correlate strongly with output phase. In parallel with this variation in synaptic strength, the firing phase of the premotor inputs to these motor neurons varies considerably across individuals. We conclude that the number (four) of inputs to each motor neuron, which each vary in strength, and the phase diversity of the temporal pattern of input from the CPG diminish the influence of individual inputs. We hypothesize that each animal arrives at a unique solution for how the network produces functional output.

Conflicting effects of excitatory synaptic and electric coupling on the dynamics of square-wave bursters.

Using two-cell and 50-cell networks of square-wave bursters, we studied how excitatory coupling of individual neurons affects the bursting output of the network. Our results show that the effects of synaptic excitation vs. electrical coupling are distinct. Increasing excitatory synaptic coupling generally increases burst duration. Electrical coupling also increases burst duration for low to moderate values, but at sufficiently strong values promotes a switch to highly synchronous bursts where further increases in electrical or synaptic coupling have a minimal effect on burst duration. These effects are largely mediated by spike synchrony, which is determined by the stability of the in-phase spiking solution during the burst. Even when both coupling mechanisms are strong, one form (in-phase or anti-phase) of spike synchrony will determine the burst dynamics, resulting in a sharp boundary in the space of the coupling parameters. This boundary exists in both two cell and network simulations. We use these results to interpret the effects of gap-junction blockers on the neuronal circuitry that underlies respiration.

Developmental reorganization of the output of a GABAergic interneuronal circuit.

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this report we demonstrate that the GABAergic R-interneuron circuit undergoes a reorganization in the chick embryo spinal cord between embryonic days 8 and 15 (E8 and E15). R-interneurons receive synaptic input from and project back to motoneurons. By stimulating motoneurons projecting in one ventral root and recording the disynaptic response from motoneurons in adjacent segments, we show that the output of the R-interneuron circuit is reorganized during development. After stimulation of the LS2 ventral root, disynaptic responses observed in whole cell recordings became more common and stronger for LS3 motoneurons and less common for the more distant LS4 motoneurons from E8 to E10. Optical studies demonstrated that R-interneurons activated by LS2 stimulation were restricted to the LS2 segment and had a small glutamatergic component at both E8 and E10, but that more R-interneurons were activated within the segment by E10. The recruitment of more LS2 R-interneurons at E10 is likely to contribute to stronger projections to LS3 motoneurons, but the fact that fewer LS4 motoneurons receive this input is more consistent with a functional refinement of the more distant projection of the GABAergic R-interneuron. Interestingly, this pattern of reorganization was not observed throughout the rostrocaudal extent of the cord, introducing the possibility that refinement could serve to remove connections between functionally unrelated interneurons and motoneurons.