The circadian clock modulates core steps in long-term memory formation in Aplysia.
The circadian clock modulates the induction of long-term sensitization (LTS) in Aplysia such that long-term memory formation is significantly suppressed when animals are trained at night. We investigated whether the circadian clock modulated core molecular processes necessary for memory formation in vivo by analyzing circadian regulation of basal and LTS-induced levels of phosphorylated mitogen-activated protein kinase (P-MAPK) and Aplysia CCAAT/enhancer binding protein (ApC/EBP). No basal circadian regulation occurred for P-MAPK or total MAPK in pleural ganglia. In contrast, the circadian clock regulated basal levels of ApC/EBP protein with peak levels at night, antiphase to the rhythm in LTS. Importantly, LTS training during the (subjective) day produced greater increases in P-MAPK and ApC/EBP than training at night. Thus, circadian modulation of LTS occurs, at least in part, by suppressing changes in key proteins at night. Rescue of long-term memory formation at night required both facilitation of MAPK and transcription in conjunction with LTS training, confirming that the circadian clock at night actively suppresses MAPK activation and transcription involved in memory formation. The circadian clock appears to modulate LTS at multiple levels. 5-HT levels are increased more when animals receive LTS training during the (subjective) day compared with the night, suggesting circadian modulation of 5-HT release. Circadian modulation also occurred downstream of 5-HT release because animals treated with 5-HT to induce LTS exhibited significantly greater LTS when treated during the (subjective) day compared with the night. Together, our studies suggest that the circadian clock modulates LTS at multiple steps and locations during the formation of long-term memory.
Lyons
Lisa C
LC
Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204-5001, USA.
Collado
Maria Sol
MS
Khabour
Omar
O
Green
Charity L
CL
Eskin
Arnold
A
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D001683:Biological Clocks / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D017952:Ganglia, Invertebrate / Q000201:enzymology; D006458:Hemolymph / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D012701:Serotonin / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D012701:Serotonin; D020928:Mitogen-Activated Protein Kinases