Hippocampus最新文献

Our everyday experiences share many overlapping features, as we often engage in repeated activities and routines. This leads to interference across our experiences, making it difficult to remember specific, unique events. Hippocampal pattern separation enables the discrimination of highly similar experiences to be stored orthogonally, especially in the face of interference. Mnemonic discrimination tasks have been designed to tax hippocampal pattern separation by including perceptually similar “lure” stimuli during memory retrieval. However, we experience vast interference beyond a single instance of overlap. Thus, a key feature of our memory system is to overcome this high interference. Furthermore, some experiences tend to be better remembered by most people than others, a feature known as memorability. However, it is unclear how memorability may impact the effect of interference on memory. To this end, we designed a mnemonic discrimination task with multiple forms of interference, such that target (repeated) and lure (similar) images of a baseline image were shown to participants during a memory test designed to increase interference during memory retrieval. We additionally varied image memorability by including memorable and forgettable images to examine interactions with interference conditions. We found that greater interference during retrieval enhanced lure discrimination for memorable images, but impaired lure discrimination for forgettable images. This suggests that interference does not uniformly impact memory, with greater interference in memory leading to exaggerated memorable and forgettable experiences.

After fear conditioning, repeated presentation of the conditioned stimulus (CS) alone produces a context-dependent extinction of learned fear. The hippocampus has a critical role in this process, but the mechanism by which contextual information encoded by the hippocampus leads to fear suppression is unknown. We hypothesize that contextual information encoded by the dorsal hippocampus supports the recall of extinction memory by the medial prefrontal cortex (mPFC). To test this hypothesis, we evaluated the oscillatory coherence and directional coupling of the hippocampus and mPFC during context-dependent extinction retrieval in a previously published experiment. In this experiment, male and female rats were subjected to auditory fear conditioning followed by fear extinction and extinction retrieval procedures. Previous analyses focused on oscillatory coupling during the CS; here, we performed new analyses to assess hippocampal-prefrontal coupling in the context in which extinction occurred. We found that, after extinction, re-exposing the animals to the extinction context produces a marked increase in dorsal hippocampal theta (6–8 Hz) oscillations. This increase was associated with enhanced coherence between the dHPC and the prelimbic (PL), but not the infralimbic (IL), division of the mPFC. Moreover, Granger causality analyses revealed that hippocampal theta oscillations preceded theta in the PL throughout the extinction retrieval session. This effect emerged during exposure to the extinction context and persisted during the presentation of the CSs and the expression of freezing behavior. Interestingly, this pattern of coherence was not observed between the dHPC and the IL. These results suggest that oscillatory coupling between the dorsal hippocampus and PL facilitates the context-dependent retrieval of the extinguished fear memory.

Hippocampal theta and gamma rhythms are often viewed as discrete channels supporting distinct cognitive operations. In particular, “gamma multiplexing” models propose that slow and fast gamma bands independently encode separate information streams or memory processes. Here, we present an alternative view: hippocampal oscillations form an interdependent process, governed by an energy cascade akin to turbulent flow across scales. In this framework, large-amplitude, low-frequency rhythms drive energy transfer to higher-frequency oscillations, rather than acting as isolated carriers of segregated information. Using laminar local field potential recordings in freely moving mice, we show that optogenetic inactivation of the medial entorhinal cortex or CA1 reduces theta power, leading to proportional reductions across the entire gamma spectrum (60–100 Hz). These data support the perspective that the putative ‘slow gamma’ component (30–50 Hz) potentially reflects higher-order theta harmonics rather than a distinct, independent rhythm. Moreover, locally generated gamma remains tightly coupled to theta, supporting an interdependent frequency spectrum modulated by network excitation. These findings challenge gamma multiplexing models and instead support an energy cascade framework, in which hippocampal gamma emerges from hierarchical, theta-driven oscillatory dynamics. Recognizing gamma as part of an interdependent, turbulence-like process reconciles contradictions in prior research and redefines how hippocampal oscillations contribute to cognition.

I outline my personal journey in hippocampal research from joining the O'Keefe lab in 1991 to the present, with a focus on earlier experimental and computational investigations of spatial cognition and neural representations in rodents, with some reference to extensions to humans and to other aspects of cognition. These recollections are organized around place cells and the role of theta rhythmicity, the importance of environmental boundaries, the operation of a wider system for spatial memory and imagery, grid cells, and the neural mechanisms of navigation in humans. I conclude with some reflections on the collaborative and exciting ecosystem that supported all of these endeavors.

Evolution sculpts the brain's sensory adaptations. Because these adaptations differ markedly across species, it is challenging for humans to fully comprehend how other animals perceive the world. For a nocturnal mouse, the subjective sensory world—its Umwelt—is dominated by odors, sounds, and textures, with visual input playing a secondary role. In contrast, the Umwelt of a diurnal primate is primarily visual, composed of colors, shapes, and hues, with less emphasis on olfaction, audition, or tactile cues. In mice and rats, hippocampal place cells are activated when the animal occupies specific locations in allocentric space. In contrast, studies in primates have identified hippocampal view cells, which respond when head-gaze is directed toward certain regions of visual space. The source of this divergence can be traced back to the evolution of mammalian species. Early mammals adapted to nocturnal environments to avoid predation by dinosaurs, becoming heavily dependent on olfaction, audition, touch, proprioception, and vestibular signals for perceiving changes in the environment, while regressing vision. However, one group of mammals started evolving stereoscopic foveal vision to capture insects and fruit in the arboreal environment. Following the mass extinction of dinosaurs, these primate ancestors transitioned to a diurnal niche, re-inventing color vision, which became their superpower. Stereo high-resolution color vision enabled primates to locate distant objects and landmarks efficiently, optimizing foraging while minimizing energy expenditure during navigation. The primate hippocampus then evolved to prioritize representations of visual scenes that support landmark-based navigation.

Intense electrical activity modifies the cellular properties of neurons to enable the nervous system to store information. The dentate gyrus (DG) plays a role in learning and memory and its principal cell type, the granule cell (GC), can fire vigorously during behavior. To explore how experience modifies GC electrophysiology, we harnessed the immediate early gene, Fos, to target a genetically encoded hybrid voltage sensor to neurons that are activated by experience and are hypothesized to encode information. Voltage imaging from these engram GCs in mouse hippocampal slices revealed distinct patterns of stimulation-evoked spiking that depended on prior experience. Compared to unchallenged mice, engram GCs from mice exposed to novelty burst more often, and have longer inter-spike intervals following the blockade of inhibition. Voltage imaging from randomly targeted non-engram GCs revealed distinct firing patterns that did not depend on novelty. Thus, experience modifies the firing of both engram and non-engram GCs in distinctly different ways. The altered bursting will tune the facilitation of transmission from engram GCs to their various postsynaptic targets, and thus redirect the flow of information through the hippocampus. The pattern of GC firing constitutes a substrate for the encoding of information and will alter how the DG processes sensory inputs.