Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons

• Published in: Nature neuroscience Vol. 21; no. 2; pp. 258 - 269
• Main Authors: Sasaki, Takuya, Piatti, Verónica C., Hwaun, Ernie, Ahmadi, Siavash, Lisman, John E., Leutgeb, Stefan, Leutgeb, Jill K.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2018; Nature Publishing Group
• Subjects: 14/63; 631/378/1595/1554; 631/378/3920; 82/51; 9/30; Action Potentials - physiology; Activity patterns; Animal Genetics and Genomics; Animal memory; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; CA3 Region, Hippocampal - cytology; Dentate gyrus; Dentate Gyrus - cytology; Dentate Gyrus - injuries; Dentate Gyrus - physiology; Granule cells; Hippocampus; Male; Maze Learning - physiology; Memory tasks; Memory, Short-Term - physiology; Mental task performance; Nerve Net - physiology; Neurobiology; Neurons; Neurons - physiology; Neurosciences; Rats; Rats, Long-Evans; Reinforcement; Reward; Rodents; Short term memory; Spatial memory; Spatial Memory - physiology; Statistics, Nonparametric; Task complexity; Time Factors
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-017-0061-5

Complex spatial working memory tasks have been shown to require both hippocampal sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We therefore asked whether DG inputs to CA3 contribute to spatial working memory by promoting SWR generation. Recordings from DG and CA3 while rats performed a dentate-dependent working memory task on an eight-arm radial maze revealed that the activity of dentate neurons and the incidence rate of SWRs both increased during reward consumption. We then found reduced reward-related CA3 SWR generation without direct input from dentate granule neurons. Furthermore, CA3 cells with place fields in not-yet-visited arms preferentially fired during SWRs at reward locations, and these prospective CA3 firing patterns were more pronounced for correct trials and were dentate-dependent. These results indicate that coordination of CA3 neuronal activity patterns by DG is necessary for the generation of neuronal firing patterns that support goal-directed behavior and memory. Sasaki et al. reveal that the dentate gyrus not only performs pattern separation but also has a direct role in organizing memory-guided behavior by coordinating the planning of future actions.