Multiple oscillators provide metastability in rhythm generation.

Biological rhythms such as cardiac and circadian rhythms arise from activity of multiple oscillators with dispersed intrinsic frequencies. It has been proposed that a stable population rhythm, fundamental to normal physiological processes, can be achieved in these systems by synchronization, through mutual entrainment, of individual oscillators. Mutual entrainment, however, is unlikely to be the mechanism underlying the generation of a stable rhythm in a population of multiple weakly coupled or uncoupled oscillators. We have recently identified such a population that is involved in the sympathetic regulation of vascular tone in a thermoregulatory circulation. In this paper, we investigate the stability of the output rhythm of these sympathetic oscillators by subjecting the system to a periodic driving force (the lung inflation cycle-related activity). We show that a population rhythm coupled to the drive can remain stable over a much wider driving frequency range compared with that of any one of its constituent oscillators. This population rhythmicity still exists despite the fact that the dominant frequencies of individual oscillators are not necessarily 1:1 frequency-locked to the drive. We provide evidence to show that this population metastability is achieved through linear and nonlinear dynamic interactions between the driving force and single sympathetic oscillators. Our study suggests that the generation of a stable population rhythm can exist even in the absence of mutual entrainment of its constituents, and this allows the population to generate a stable and flexible patterned response.