Iterative Metaplasticity Across Timescales: How Circadian, Ultradian, and Infradian Rhythms Modulate Memory Mechanisms

Abstract

Work in recent years has provided strong evidence for the modulation of memory function and neuroplasticity mechanisms across circadian (daily), ultradian (shorter-than-daily), and infradian (longer-than-daily) timescales. Despite rapid progress, however, the field has yet to adopt a general framework to describe the overarching role of biological rhythms in memory. To this end, Iyer and colleagues introduced the term iterative metaplasticity, which they define as the "gating of receptivity to subsequent signals that repeats on a cyclic timebase." The central concept is that the cyclic regulation of molecules involved in neuroplasticity may produce cycles in neuroplastic capacity-that is, the ability of neural cells to undergo activity-dependent change. Although Iyer and colleagues focus on the circadian timescale, we think their framework may be useful for understanding how biological rhythms influence memory more broadly. In this review, we provide examples and terminology to explain how the idea of iterative metaplasticity can be readily applied across circadian, ultradian, and infradian timescales. We suggest that iterative metaplasticity may not only support the temporal niching of neuroplasticity processes but also serve an essential role in the maintenance of memory function.

Keywords: circadian rhythms; infradian rhythms; iterative metaplasticity; neuroplastic capacity; neuroplasticity; ultradian rhythms.

Figure 1. Sources of iterative metaplasticity across timescales.

Iterations in neuroplastic capacity may occur on ultradian (hourglass), circadian (solar cycle), and infradian (calendar) timescales. On each timescale, iterations generated by endogenous cyclic signals must be distinguished from iterations generated by environmental cyclic signals.

Figure 2. Examples of iterative metaplasticity across timescales.

On the ultradian timescale, work in mouse hippocampal neurons suggests glucocorticoid-dependent oscillations in AMPA receptor membrane localization that create oscillations in the capacity for long-term potentiation (Sarabdjitsingh et al. 2014). On the circadian timescale, studies of Drosophila demonstrate clock-regulated rhythms in the transcription of plasticity-related genes (Claridge-Chang et al. 2001; Cirelli et al. 2004). On the infradian timescale, canary research illustrates seasonal differences in the formation of perineuronal nets, which stabilize synapses (Cornez, Collignon, et al. 2020). Across timescale and organism, iterations in such basal neural features generate iterations in the capacity for activity-dependent plasticity and memory.