Clocking In Time to Gate Memory Processes: The Circadian Clock Is Part of the Ins and Outs of Memory

Abstract

Learning, memory consolidation, and retrieval are processes known to be modulated by the circadian (circa: about; dies: day) system. The circadian regulation of memory performance is evolutionarily conserved, independent of the type and complexity of the learning paradigm tested, and not specific to crepuscular, nocturnal, or diurnal organisms. In mammals, long-term memory (LTM) formation is tightly coupled to de novo gene expression of plasticity-related proteins and posttranslational modifications and relies on intact cAMP/protein kinase A (PKA)/protein kinase C (PKC)/mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling. These memory-essential signaling components cycle rhythmically in the hippocampus across the day and night and are clearly molded by an intricate interplay between the circadian system and memory. Important components of the circadian timing mechanism and its plasticity are members of the Period clock gene family (Per1, Per2). Interestingly, Per1 is rhythmically expressed in mouse hippocampus. Observations suggest important and largely unexplored roles of the clock gene protein PER1 in synaptic plasticity and in the daytime-dependent modulation of learning and memory. Here, we review the latest findings on the role of the clock gene Period 1 (Per1) as a candidate molecular and mechanistic blueprint for gating the daytime dependency of memory processing.

The CBP KIX domain regulates long-term memory and circadian activity

“…Using enrichment network analysis after annotating the upregulated DEGs through the KEGG pathway database, we found that the most significant change occurred in the MAPK signaling pathway (also known as the Ras-Raf-MEK-ERK pathway) (Fig 3c). Circadian genes have recently been shown to be involved in hippocampus-dependent memory (56,57), and the lack of functional Per1 in the hippocampus impairs object location memory (58) and LTP (59). As predicted, based upon the downregulation of circadian pathways we observed after learning in CBP KIX/KIX mice, we also found pathways related to circadian rhythm and circadian entrainment to be upregulated following spatial learning in WT mice.…”

The CBP KIX domain regulates long-term memory and circadian activity

“…3 c). Circadian genes have recently been shown to be involved in hippocampus-dependent memory [ 56 , 57 ], and the lack of functional Per1 in the hippocampus impairs object location memory [ 58 ] and LTP [ 59 ]. As predicted, based upon the downregulation of circadian pathways we observed after learning in CBP KIX/KIX mice, we also found pathways related to circadian rhythm and circadian entrainment to be upregulated following spatial learning in WT mice.…”

Circadian modulation of neurons and astrocytes controls synaptic plasticity in hippocampal area CA1

“…Here, more than 10% of genes and proteins show circadian fluctuations (Debski et al, 2017) and are associated with changes in synaptic excitability (Barnes et al, 1977). Learning and memory formation, two functions that are conserved across species and that in mammals rely on the activity of the hippocampal formation, are also modulated by circadian rhythms (Gerstner et al, 2009;Rawashdeh et al, 2018;Ruby et al, 2008;Shimizu et al, 2016;Smarr et al, 2014;Snider et al, 2016). For example, mice trained to context fear conditioning protocols acquire the conditioning more slowly if trained during the dark (D) phase of the circadian cycle (ZT12-24) (Chaudhury and Colwell, 2002), a time when long-term plasticity at Schaffer collateral synapses is also reduced Abzug, 1977, 1978).…”