The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1–3-Hz “low theta” band increases when viewing subsequently remembered object–location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

Ketamine has been reported to be an efficacious antidepressant for major depressive disorder and posttraumatic stress disorder. Most recently, ketamine has also been shown to be prophylactic against stress-induced depressive-like behavior in mice. It remains unknown, however, when ketamine should be administered relative to a stressor in order to maximize its antidepressant and/or prophylactic effects. Moreover, it is unknown whether ketamine can be prophylactic against subsequent stressors. We systematically administered ketamine at different time points relative to a fear experience, in order to determine when ketamine is most effective at reducing fear expression or preventing fear reactivation. Using a contextual fear conditioning (CFC) paradigm, mice were administered a single dose of saline or ketamine (30 mg/kg) at varying time points before or after CFC. Mice administered prophylactic ketamine 1 week, but not 1 month or 1 h before CFC, exhibited reduced freezing behavior when compared with mice administered saline. In contrast, ketamine administration following CFC or during extinction did not alter subsequent fear expression. However, ketamine administered before reinstatement increased the number of rearing bouts in an open field, possibly suggesting an increase in attentiveness. These data indicate that ketamine can buffer a fear response when given a week before as prophylactic, but not when given immediately before or after a stress-inducing episode. Thus, ketamine may be most useful in the clinic if administered in a prophylactic manner 1 week before a stressor, in order to protect against heightened fear responses to aversive stimuli.

Highlights d Epilepsy patients performed a spatial navigation task during single-neuron recordings d Neuronal firing in the medial temporal lobe represents spatial target locations d Single-neuron activity does not represent the subject's own location in this task d Neuronal activity also varied with heading direction and order of navigation periods

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Spatial navigation relies on neural systems that encode spatial information relative to the external world or in relation to the navigating organism. Ever since the proposal of cognitive maps, the neuroscience of spatial navigation has focused on allocentric (world-referenced) neural representations such as place cells. Here, using single-neuron recordings during virtual 30 navigation, we reveal a neural code of egocentric (self-centered) spatial information in the human brain: We describe "anchor cells", which represent egocentric directions towards local "anchor points" distributed across the environmental center and periphery. Anchor-cell activity was abundant in parahippocampal cortex, signaled anchor-point distances, and showed memory modulation. Anchor cells may thus facilitate egocentric navigation 35 strategies, may assist in transforming percepts into allocentric spatial representations, and may underlie the first-person perspective in episodic memories. One Sentence Summary:Anchor cells in the human brain provide the neural basis for a self-centered coordinate 40 system during spatial navigation.3 Main text:Detailed neural representations of space form the neurobiological basis of successful navigation and accurate spatial memory. Traditionally, the neuroscience of spatial navigation has focused on allocentric representations, which encode spatial information in relation to the 45 external world: the place field of a place cell may be located in the "northeast" corner of an environment (1, 2), a head-direction cell may activate whenever navigating "south" (3), and a boundary vector/border cell may respond to a spatial boundary located "west" (4, 5). However, spatial environments are primarily experienced from a first-person, egocentric perspective -requiring neural codes that provide spatial information in relation to the self. 50 Via transformation circuits (6, 7), egocentric representations (8-10) may then be converted into their allocentric counterparts (4, 5, 11) for abstract knowledge and long-term storage (12).Despite abundant behavioral evidence that humans employ egocentric spatial information to accomplish wayfinding (12-15), little is known about the neural basis of egocentric spatial 55 representations in humans. Here, we hypothesized that neurons in human medial temporal lobe (MTL) keep track of the instantaneous relationship between the navigating subject and proximal areas of the environment. Specifically, we targeted the identification of "anchor cells" whose activity encodes the subject's egocentric direction towards local reference points (termed "anchor points"). Such a coding scheme would be instrumental for egocentric 60 navigation, because it provides orientation in relation to the proximal spatial layout.To detect and characterize human anchor cells, we recorded single-neuron activity from the MTL of ten neurosurgical epilepsy patients (table S1), while patients performed an objectlocation memory task in a virtual environment (Fig. 1, A and B). In this task (16), patients learne...