A stable hippocampal representation of a space requires its direct experience

Abstract

In humans and other mammals, the hippocampus is critical for episodic memory, the autobiographical record of events, including where and when they happen. When one records from hippocampal pyramidal neurons in awake, behaving rodents, their most obvious firing correlate is the animal's position within a particular environment, earning them the name "place cells." When an animal explores a novel environment, its pyramidal neurons form their spatial receptive fields over a matter of minutes and are generally stable thereafter. This experience-dependent stabilization of place fields is therefore an attractive candidate neural correlate of the formation of hippocampal memory. However, precisely how the animal's experience of a context translates into stable place fields remains largely unclear. For instance, we still do not know whether observation of a space is sufficient to generate a stable hippocampal representation of that space because the animal must physically visit a spot to demonstrate which cells fire there. We circumvented this problem by comparing the relative stability of place fields of directly experienced space from merely observed space following blockade of NMDA receptors, which preferentially destabilizes newly generated place fields. This allowed us to determine whether place cells stably represent parts of the environment the animal sees, but does not actually occupy. We found that the formation of stable place fields clearly requires direct experience with a space. This suggests that place cells are part of an autobiographical record of events and their spatial context, consistent with providing the "where" information in episodic memory.learning | plasticity | cognitive map | remapping | consolidation T he hippocampus is clearly central to mammalian learning and memory (1), and it is just as clear that an animal's position in space is by far the most obvious firing correlate of hippocampal neurons in awake, behaving rodents (2). However, the precise relationship between memory and place cells is less clear, making the study of the processes governing the formation of place fields particularly interesting. Consistent with the central role for the hippocampus in memory, the balance of experimental evidence supports the idea that place fields are constructed and stabilized by the animal's experience of that space. For example, place cells "remap" (i.e., change to unpredictable locations and/or change their firing rate) in response to even small changes in the sensory environment (3) or even changes in the animal's ongoing behavior (4, 5). Moreover, place fields are quite labile in novel environments until the animal has experienced the environment for several minutes (6, 7). Finally, inhibitors of synaptic plasticity prevent the long-term maintenance (i.e., destabilize) of place fields in novel but not familiar environments (8, 9).However, recent studies have forced a reexamination of the debate. First, place cells in weanling rats show some adult-like spatial tuning during the animals' first sp...

Hippocampal Sequences and the Cognitive Map

“…Alternatively, pre-play could be interpreted as a constructive process, involved in allocating representations to nearby, but novel, regions of space. Interestingly, while observation alone is not suffi cient for the development of stable place cells covering unvisited portions of the environment [ 94 ], the dorsal hippocampus has been implicated in processing visible but inaccessible objects [ 95 ]. It is possible, as suggested by Rowland and colleagues [ 94 ], that pre-play serves to establish a rough, approximate spatial representation that is subsequently refi ned and bound to prominent environmental features upon direct physical experience.…”

“…Interestingly, while observation alone is not suffi cient for the development of stable place cells covering unvisited portions of the environment [ 94 ], the dorsal hippocampus has been implicated in processing visible but inaccessible objects [ 95 ]. It is possible, as suggested by Rowland and colleagues [ 94 ], that pre-play serves to establish a rough, approximate spatial representation that is subsequently refi ned and bound to prominent environmental features upon direct physical experience. Although the behavioral implications of pre-play are not yet clear, this sort of representation could be useful in both the planning and constructive cognitive map functions outlined in this chapter.…”

Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum

“…Second, through interconnections with the entorhinal cortex and inferior parietal cortex, the presubiculum plays an important role in visual spatial integration, navigation, and memory (60). This system for spatial navigation and memory provides a set of processes that likely form the basis for other types of memory, including episodic autobiographical memory (61). Memory problems have often been reported in individuals with maltreatment histories (62,63).…”

Characterization of the guinea pig animal model and subsequent comparison of the behavioral effects of selective dopaminergic drugs and methamphetamine

“…However, with regard to understanding complex behaviors that are readily translatable to human behaviors or studying human psychiatric disorders like anxiety, mnemonic disorders, and depression, limitations of using mice and rats have been acknowledged (Kalueff et al, ; Spruijt and Visser, ; Tescott and Nestler, ; Wahlsten and Rustay, ). For example, an increasing number of studies report that animal attentiveness is a prerequisite for the development of robust visuospatial and olfactory representations in the hippocampus (Muzzio et al, ; Rowland et al, ). However, it is difficult to measure spontaneous behavior reflective of paying “attention” towards new objects and environments in both mice and rats (Antunes and Biala, ; Clark and Martin, ; Clark and Squire, ; Fantz, ; Pascalis and de Haan, ).…”