Joshua A. Gordon

Long-range synchrony between distant brain regions accompanies multiple forms of behavior. This review compares and contrasts the methods by which long-range synchrony is evaluated in both humans and model animals. Three examples of behaviorally relevant long-range synchrony are discussed in detail: gamma-frequency synchrony during visual perception, hippocampal-prefrontal synchrony during working memory, and prefrontal-amygdala synchrony during anxiety. Implications for circuit mechanism, translation, and clinical relevance are discussed.

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.

The rodent medial prefrontal cortex (mPFC) is critical for spatial working memory (SWM), but the underlying neural processes are incompletely understood. During SWM tasks, neural activity in the mPFC becomes synchronized with theta oscillations in the hippocampus, and the strength of hippocampal–prefrontal synchrony is correlated with behavioral performance. However, to what extent the mPFC generates theta oscillations and whether they are also modulated by SWM remains unclear. Furthermore, it is not known how theta oscillations in the mPFC are synchronized with theta oscillations in the hippocampus. Although the ventral hippocampus (vHPC) projects directly to the mPFC, previous studies have only examined synchrony between the mPFC and the dorsal hippocampus (dHPC), with which it is not directly connected. To address these issues, we recorded simultaneously from the dHPC, vHPC, and mPFC of mice performing a SWM task in a T-maze. The local field potential recorded in the mPFC displayed robust theta oscillations that were reflected in local measures of neuronal activity and modulated by SWM performance. mPFC theta oscillations were also synchronized with theta oscillations in both the vHPC and dHPC, and the magnitude of theta synchrony was modulated by SWM. Removing the influence of the vHPC either computationally (through partial correlations) or experimentally (through pharmacological inactivation) reduced theta synchrony between the mPFC and dHPC. These results reveal theta oscillations as a prominent feature of neural activity in the mPFC and a candidate neural mechanism underlying SWM. Furthermore, our results suggest that the vHPC plays a major role in synchronizing theta oscillations in the mPFC and the hippocampus.