Forgetting unrelated spatial memories through suppression-induced amnesia

CaMKII Activation in the Entorhinal Cortex Disrupts Previously Encoded Spatial Memory

It has been hypothesized that differential processing occurs along the longitudinal (anterior-posterior) axis of the hippocampus. One hypothesis is that spatial memory (during both encoding and retrieval) is associated with the posterior hippocampus. An alternative hypothesis is that memory encoding (either spatial or nonspatial) is associated with the anterior hippocampus and memory retrieval is associated with the posterior hippocampus. Of importance, during spatial memory encoding, the spatial-posterior hypothesis predicts posterior hippocampal involvement, whereas the encoding-retrieval hypothesis predicts anterior hippocampal involvement. To distinguish between these hypotheses, we conducted a coordinate-based fMRI activation likelihood estimation (ALE) meta-analysis of 26 studies (with a total of 435 participants) that reported hippocampal activity during spatial memory encoding and/or spatial memory retrieval. Both spatial memory encoding and spatial memory retrieval produced extensive activity along the longitudinal axis of the hippocampus as well as the entorhinal cortex, the perirhinal cortex, and the parahippocampal cortex. Critically, the contrast of spatial memory encoding and spatial memory retrieval produced activations in both the anterior hippocampus and the posterior hippocampus. That spatial memory encoding produced activity in both the anterior and posterior hippocampus can be taken to reject strict forms of the spatial-posterior hypothesis, which stipulates that all forms of spatial memory produce activity in the posterior hippocampus, and the encoding-retrieval hypothesis, which stipulates that all forms of encoding versus retrieval produce activity in only the anterior hippocampus. Our results indicate that spatial memory encoding can involve the anterior hippocampus and the posterior hippocampus.

Spatial location and pathway memory compared in the reaching vs. walking domains

To clarify the specific contribution of the medial temporal lobe structures in spatial memory, we tested monkeys (Macaca mulatta) with sham operations and with lesions of either the hippocampal formation, areas TH/TF or perirhinal cortex on two versions of the visual-paired comparison task, measuring Spatial Location, and Object-in-Place associations. In the Spatial Location version, the comparison was between two identical objects presented simultaneously in a familiar and a novel location. In the Object-in-Place version, the comparison was between an image consisting of five objects and another image showing the same five objects, but with the position of 2, 3, or 4 of the objects rearranged. Finally, a VPC-Control task was given to animals with hippocampal and perirhinal lesions, in which the comparison was between an image consisting of five objects and another image showing four of the five familiar objects and a new one. Perirhinal lesions yielded no deficit in the Spatial Location task and a deficit in the Object-in-Place task associated with a deficit in the VPC-control task, suggesting that this cortical area does not participate in spatial memory unless the stimuli have overlapping features. Areas TH/TF lesions produced a deficit in both Spatial Location and Object-in-Place tasks, whereas the hippocampal lesions resulted in a deficit of Object-in-Place associations only. The data showed that the hippocampal formation, areas TH/TF, and perirhinal cortex appear to contribute interactively to object and spatial memory processes.

Dissociation of spatial and contextual memory encoding under fear and pain in mice.

The role of the dorsal CA3 hippocampal subregion in spatial working memory and pattern separation

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n = 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8-arm radial arm maze win-shift task. Comparing rats’ behavior in the two arm types showed that rearing frequency was not changed but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n = 6 rats). Optogenetic inhibition of cholinergic neurons during the pre-trial waiting phase had no significant effect on rearing, indicating a context-specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing.

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n= 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8-arm radial arm maze win-shift task. Comparing rats' behaviour in the two arm types showed that rearing frequency was not changed, but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n= 6 rats). Optogenetic inhibition of cholinergic neurons during the pretrial waiting phase had no significant effect on rearing, indicating a context-specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing.

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 minutes created a short-term memory (weak) that cannot be retrieved one day later, whereas 10 minutes exploration created a long-term memory (strong) that can be retrieved one day later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval one day later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 hours. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.Significance statement Increased levels of dopamine have been related to cognitive enhancement. Hippocampal dopamine elevation caused by novelty exposure has been proposed as a strategy to enhance memory based on the observation that surprising events create flashbulb memories that are remembered for long time. However, hyperdopaminergic levels could also underlie maladaptive memories, such as non-desired preservation of traumatic experiences. Our experiments show that dopamine elevation in the dorsal hippocampus during the encoding of spatial memories has paradoxical effects, while the enhancement of weak memories allows their retrieval, the dopaminergic modulation of strong memories limits the ability to modify preexisting spatial memories by changes in the environment. We conclude that cognitive enhancement through dopamine boosting must consider diverse aspects of memory formation.

The anterior hippocampus is associated with spatial memory encoding

In rodents, ethanol produces a greater impact on the ability to perform spatial reference memory tasks than nonspatial reference memory tasks. Such evidence may reflect a selective disruption in the use of previously acquired spatial information. However, a nonmnemonic explanation has yet to be ruled out Tasks used to study ethanol's effects on spatial memory commonly require subjects to utilize distal, or extramaze, cues to respond correctly. In contrast, many previously used nonspatial tasks could be solved using cues located on the maze itself. Because ethanol has been shown to disrupt sensory processing, it is possible that previously observed differences in the effects of ethanol on spatial and nonspatial performance were actually due to differences in the proximity of relevant cues in the spatial and nonspatial tasks and not to a selective disruption in spatial memory. The present study compares the effects of ethanol on the performance of spatial and nonspatial reference memory tasks that require subjects to discriminate among extramaze cues for correct responding. Subjects were trained while sober to navigate to a goal arm on a 12-arm maze. In the spatial task, the goal arm was defined by its location with respect to a number of extramaze cues. In the nonspatial task, the goal arm was defined by the presence of a single extramaze cue located directly beyond the end of the arm. Subjects were tested under 1 of 4 doses of ethanol (0.0, 0.7, 1.4, and 2.1 g/kg). Performance on the nonspatial task was more resistant to the effects of ethanol than performance on the spatial task. The results suggest that differences in the effects of ethanol on spatial and nonspatial performance are not due to differences in the proximity of relevant cues in previously used spatial and nonspatial tasks.

P192 Investigating the role of the parietal and prefrontal cortices in spatial working memory using transcranial direct current stimulation

This study examined how spatial working memory and visual (object) working memory interact, focusing on two related questions: First, can these systems function independently from one another? Second, under what conditions do they operate together? In a dual-task paradigm, participants attempted to remember locations in a spatial working memory task and colored objects in a visual working memory task. Memory for the locations and objects was subject to independent working memory storage limits, which indicates that spatial and visual working memory can function independently from one another. However, additional experiments revealed that spatial working memory and visual working memory interact in three memory contexts: when retaining (1) shapes, (2) integrated color-shape objects, and (3) colored objects at specific locations. These results suggest that spatial working memory is needed to bind colors and shapes into integrated object representations in visual working memory. Further, this study reveals a set of conditions in which spatial and visual working memory can be isolated from one another.

Temporary inactivation of the supramammillary area impairs spatial working memory and spatial reference memory retrieval

<p><strong>Many bird species cache food items for later retrieval, a behaviour requiring spatial memory to accomplish. Several studies have now linked individual performance on a spatial memory task with reproductive success in wild food-storing birds, providing evidence that selection acts on spatial memory. However, it remains uncertain whether caching is the specific target of this selection, and whether individual differences in spatial memory ability are also reflected in caching behaviour. Furthermore, it is also unclear whether a single task can accurately quantify the spatial cognitive abilities used by birds during caching. In this thesis, I investigated the interface of spatial memory, caching behaviour, and reproductive success in a wild food-storing bird, the North Island robin (Petroica longipes), henceforth referred to by their Māori name, toutouwai. Using an established study population, I first quantified the birds’ caching behaviour, finding that individuals consistently differed in their storing along a ‘caching syndrome’. ‘Clump-caching’ birds rapidly created clusters of nearby cache sites, while ‘scatter-caching’ birds spent longer selecting a greater number of distant sites when storing food. I then ran a three-task spatial memory test battery on the same birds, investigating individual variation in 1) preference for spatial cues or local visual cues, 2) the ability to learn to discriminate a single rewarded position in an array, and 3) spatial working memory for recently depleted positions in an array. No convergent validity was found between any of the tasks, suggesting that spatial memory in toutouwai may consist of several modules rather than a single general ability. Finally, I compared individuals’ spatial memory task performance and individual caching behaviour with each other, and with three proxies for fitness: breeding season start date, number of independent offspring, and survival over the breeding season. Caching behaviour covaried with spatial discrimination learning, with ‘clump-caching’ males showing significantly worse spatial memory that ‘scatter-cachers’. However, there was no effect of caching or spatial memory on any fitness proxy. Overall, my findings represent the first field study to provide detailed spatiotemporal caching measures, multiple spatial memory measures, and fitness proxies have been integrated in a wild food-storing bird. The results suggest that individual differences in the spatiotemporal aspects of caching may not directly influence fitness in toutouwai, but do not rule out the influence of other caching measures, or other behaviours involving spatial memory.</strong></p>