Paul A. Dudchenko

The global record of memory in hippocampal neuronal activity

In humans the hippocampal region of the brain is crucial for declarative or episodic memory for a broad range of materials. In contrast, there has been controversy over whether the hippocampus mediates a similarly general memory function in other species, or whether it is dedicated to spatial memory processing. Evidence for the spatial view is derived principally from the observations of ‘place cells’—hippocampal neurons that fire whenever the animal is in a particular location in its environment, or when it perceives a specific stimulus or performs a specific behaviour in a particular place. We trained rats to perform the same recognition memory task in several distinct locations in a rich spatial environment and found that the activity of many hippocampal neurons was related consistently to perceptual, behavioural or cognitive events, regardless of the location where these events occurred. These results indicate that non-spatial events are fundamental elements of hippocampal representation, and support the view that, across species, the hippocampus has a broad role in information processing associated with memory.

An overview of the tasks used to test working memory in rodents

In rodents, working memory is a representation of an object, stimulus, or spatial location that is typically used within a testing session, but not between sessions, to guide behaviour. In this review we consider a number of the tasks used to assess this type of memory in the rodent, and highlight some of their limitations. Although the concept of working memory as applied to rodents has its origin in the experiments of David Olton and Werner Honig in the 1970s, many earlier experiments assessed the same type of memory under the guise of delayed reaction or alternation paradigms. We revisit these early tasks, and also consider the nature of working memory used on maze tasks, operant box based tasks, and non-spatial delayed non-matching to sample paradigms.

How do animals actually solve the T maze

Rats were trained on a reinforced, delayed alternation T-maze task in the presence (cue group) or absence (no-cue group) of salient extramaze landmarks. A surprising finding was that the acquisition and memory performance of the 2 groups did not differ. Manipulations of the extramaze landmarks for the cue group suggested that, although landmarks were used to guide behavior, other sources of information were also used normally. The no-cue group was able to perform the task at above-chance levels even when extramaze, intramaze, and inertial sources of orientation were manipulated. These results suggest that memory performance on the T maze does not rely exclusively on the processing of allocentric spatial relationships in the maze environment.

Hippocampal CA1 place cells encode intended destination on a maze with multiple choice points.

The hippocampus encodes both spatial and nonspatial aspects of a rats ongoing behavior at the single-cell level. In this study, we examined the encoding of intended destination by hippocampal (CA1) place cells during performance of a serial reversal task on a double Y-maze. On the maze, rats had to make two choices to access one of four possible goal locations, two of which contained reward. Reward locations were kept constant within blocks of 10 trials but changed between blocks, and the session of each day comprised three or more trial blocks. A disproportionate number of place fields were observed in the start box and beginning stem of the maze, relative to other locations on the maze. Forty-six percent of these place fields had different firing rates on journeys to different goal boxes. Another group of cells had place fields before the second choice point, and, of these, 44% differentiated between journeys to specific goal boxes. In a second experiment, we observed that rats with hippocampal damage made significantly more errors than control rats on the Y-maze when reward locations were reversed. Together, these results suggest that, at the start of the maze, the hippocampus encodes both current location and the intended destination of the rat, and this encoding is necessary for the flexible response to changes in reinforcement contingencies.

Hippocampal place cells encode intended destination, and not a discriminative stimulus, in a conditional T-maze task

The firing of hippocampal place cells encodes instantaneous location but can also reflect where the animal is heading (prospective firing), or where it has just come from (retrospective firing). The current experiment sought to explicitly control the prospective firing of place cells with a visual discriminada in a T‐maze. Rats were trained to associate a specific visual stimulus (e.g., a flashing light) with the occurrence of reward in a specific location (e.g., the left arm of the T). A different visual stimulus (e.g., a constant light) signaled the availability of reward in the opposite arm of the T. After this discrimination had been acquired, rats were implanted with electrodes in the CA1 layer of the hippocampus. Place cells were then identified and recorded as the animals performed the discrimination task, and the presentation of the visual stimulus was manipulated. A subset of CA1 place cells fired at different rates on the central stem of the T depending on the animals intended destination, but this conditional or prospective firing was independent of the visual discriminative stimulus. The firing rate of some place cells was, however, modulated by changes in the timing of presentation of the visual stimulus. Thus, place cells fired prospectively, but this firing did not appear to be controlled, directly, by a salient visual stimulus that controlled behavior.

Aging, spatial behavior and the cognitive map

Hippocampal neurons are thought to form a cognitive map of the environment based on multiple cues. A new study shows that young animals switch between cues more easily than aged animals and also perform better on a spatial learning task.

Place Field Repetition and Spatial Learning in a Multicompartment Environment

Recent studies have shown that place cells in the hippocampus possess firing fields that repeat in physically similar, parallel environments. These results imply that it should be difficult for animals to distinguish parallel environments at a behavioral level. To test this, we trained rats on a novel odor‐location task in an environment with four parallel compartments which had previously been shown to yield place field repetition. A second group of animals was trained on the same task, but with the compartments arranged in different directions, an arrangement we hypothesised would yield less place field repetition. Learning of the odor‐location task in the parallel compartments was significantly impaired relative to learning in the radially arranged compartments. Fewer animals acquired the full discrimination in the parallel compartments compared to those trained in the radial compartments, and the former also required many more sessions to reach criterion compared to the latter. To confirm that the arrangement of compartments yielded differences in place cell repetition, in a separate group of animals we recorded from CA1 place cells in both environments. We found that CA1 place cells exhibited repeated fields across four parallel local compartments, but did not do so when the same compartments were arranged radially. To confirm that the differences in place field repetition across the parallel and radial compartments depended on their angular arrangement, and not incidental differences in access to an extra‐maze visual landmark, we repeated the recordings in a second set of rats in the absence of the orientation landmark. We found, once again, that place fields showed repetition in parallel compartments, and did not do so in radially arranged compartments. Thus place field repetition, or lack thereof, in these compartments was not dependent on extra‐maze cues. Together, these results imply that place field repetition constrains spatial learning.

The neural substrates of deliberative decision making: contrasting effects of hippocampus lesions on performance and vicarious trial-and-error behavior in a spatial memory task and a visual discrimination task

Vicarious trial-and-errors (VTEs) are back-and-forth movements of the head exhibited by rodents and other animals when faced with a decision. These behaviors have recently been associated with prospective sweeps of hippocampal place cell firing, and thus may reflect a rodent model of deliberative decision-making. The aim of the current study was to test whether the hippocampus is essential for VTEs in a spatial memory task and in a simple visual discrimination (VD) task. We found that lesions of the hippocampus with ibotenic acid produced a significant impairment in the accuracy of choices in a serial spatial reversal (SR) task. In terms of VTEs, whereas sham-lesioned animals engaged in more VTE behavior prior to identifying the location of the reward as opposed to repeated trials after it had been located, the lesioned animals failed to show this difference. In contrast, damage to the hippocampus had no effect on acquisition of a VD or on the VTEs seen in this task. For both lesion and sham-lesion animals, adding an additional choice to the VD increased the number of VTEs and decreased the accuracy of choices. Together, these results suggest that the hippocampus may be specifically involved in VTE behavior during spatial decision making.

Odor supported place cell model and goal navigation in rodents

Experiments with rodents demonstrate that visual cues play an important role in the control of hippocampal place cells and spatial navigation. Nevertheless, rats may also rely on auditory, olfactory and somatosensory stimuli for orientation. It is also known that rats can track odors or self-generated scent marks to find a food source. Here we model odor supported place cells by using a simple feed-forward network and analyze the impact of olfactory cues on place cell formation and spatial navigation. The obtained place cells are used to solve a goal navigation task by a novel mechanism based on self-marking by odor patches combined with a Q-learning algorithm. We also analyze the impact of place cell remapping on goal directed behavior when switching between two environments. We emphasize the importance of olfactory cues in place cell formation and show that the utility of environmental and self-generated olfactory cues, together with a mixed navigation strategy, improves goal directed navigation.

Place cells on a maze encode routes rather than destinations

Hippocampal place cells fire at different rates when a rodent runs through a given location on its way to different destinations. However, it is unclear whether such firing represents the animal’s intended destination or the execution of a specific trajectory. To distinguish between these possibilities, Lister Hooded rats (n = 8) were trained to navigate from a start box to three goal locations via four partially overlapping routes. Two of these led to the same goal location. Of the cells that fired on these two routes, 95.8% showed route-dependent firing (firing on only one route), whereas only two cells (4.2%) showed goal-dependent firing (firing similarly on both routes). In addition, route-dependent place cells over-represented the less discriminable routes, and place cells in general over-represented the start location. These results indicate that place cell firing on overlapping routes reflects the animal’s route, not its goals, and that this firing may aid spatial discrimination. DOI: http://dx.doi.org/10.7554/eLife.15986.001