Hippocampal–prefrontal input supports spatial encoding in working memory

• Published in: Nature (London) Vol. 522; no. 7556; pp. 309 - 314
• Main Authors: Spellman, Timothy, Rigotti, Mattia, Ahmari, Susanne E., Fusi, Stefano, Gogos, Joseph A., Gordon, Joshua A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.06.2015; Nature Publishing Group
• Subjects: 631/378/1595/1554; 631/378/1595/1637; 631/378/1595/2618; 64/60; 9/10; 9/26; 9/30; Action Potentials; Afferent Pathways - physiology; Animals; Brain; Cognition & reasoning; Cues; Hippocampus (Brain); Hippocampus - cytology; Hippocampus - physiology; Humanities and Social Sciences; Male; Memory; Memory, Short-Term - physiology; Mice; Models, Neurological; multidisciplinary; Optogenetics; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - cytology; Prefrontal Cortex - physiology; Science; Short-term memory; Space Perception - physiology; Spatial Memory - physiology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature14445

Spatial working memory, the caching of behaviourally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. Although the prefrontal cortex and hippocampus are known to contribute jointly to successful spatial working memory, the anatomical pathway and temporal window for the interaction of these structures critical to spatial working memory has not yet been established. Here we find that direct hippocampal–prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues in mice. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal–prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory. Spatial working memory is known to involve the prefrontal cortex and the hippocampus, but the specificities of the connection have been unclear; now, a direct path between these two areas is defined that is necessary for the encoding of spatial cues in mice, but is not required for the maintenance or retrieval of these cues. The nature of spatial memory Spatial working memory is maintained through a coordination of activity between prefrontal brain areas and the hippocampus, but it has been unclear what the precise anatomical connections between these areas are and on what time scales they operate. Here, Joshua Gordon and colleagues define a direct path between prefrontal cortex and hippocampus that is necessary for proper encoding of spatial cues, but is not required for maintenance and retrieval of these cues. Hippocampal information flows to neural units in the prefrontal cortex during the encoding phases of spatial working memory tasks, with successful encoding requiring synchrony between the two brain structures in the gamma-frequency band of network activity. These findings demonstrate the critical importance of hippocampal–prefrontal direct input in the continuous updating of spatial information.