Plasticity manifolds and degeneracy govern circadian oscillations of neuronal intrinsic properties in the suprachiasmatic nucleus

iScience. 2023 Mar 27;26(4):106503. doi: 10.1016/j.isci.2023.106503. eCollection 2023 Apr 21.

Abstract

A heterogeneous neuronal population in the suprachiasmatic nucleus (SCN) sustains a cell-autonomous code for circadian time, implemented by firing-rate plasticity involving multiple ion channels. How do SCN neurons undergo stable firing-rate transitions if several ion channels change simultaneously in a heterogeneous neuronal population? Here, we addressed this question by building a heterogeneous population of SCN model neurons, each allowed to undergo one complete circadian cycle through multiple possible routes. We found that SCN neurons could achieve signature electrophysiological characteristics (day-like or night-like) despite pronounced heterogeneity in ion-channel conductances. Furthermore, for any neuron, disparate combinations of ion-channel plasticity yielded valid day-to-night or night-to-day transitions. Finally, nonlinear dimensionality reduction analyses on valid plasticity spaces revealed a low-dimensional plasticity manifold in day-to-night transitions, but not in night-to-day transitions. Our analyses unveil a synthesis of the degeneracy and the plasticity manifold frameworks that provides robustness and flexibility in achieving precise transitions despite widespread heterogeneities.

Keywords: Neuroscience.