Lateral entorhinal cortex lesions impair local spatial frameworks

A prominent theory in the neurobiology of memory processing is that episodic memory is supported by contextually gated spatial representations in the hippocampus formed by combining spatial information from medial entorhinal cortex (MEC) with non-spatial information from lateral entorhinal cortex (LEC). However, there is a growing body of evidence from lesion and single-unit recording studies in rodents suggesting that LEC might have a role in encoding space, particularly the current and previous locations of objects within the local environment. Landmarks, both local and global, have been shown to control the spatial representations hypothesised to underlie cognitive maps. Consequently, it has recently been suggested that information processing within this network might be organized with reference to spatial scale with LEC and MEC providing information about local and global spatial frameworks respectively. In the present study, we trained animals to search for food using either a local or global spatial framework. Animals were re-tested on both tasks after receiving excitotoxic lesions of either the MEC or LEC. LEC lesioned animals were impaired in their ability to learn a local spatial framework task. LEC lesioned animals were also impaired on an object recognition task involving multiple local features but unimpaired at recognizing a single familiar object. Together, this suggests that LEC is involved in associating features of the local environment. However, neither LEC nor MEC lesions impaired performance on the global spatial framework task.Publisher PDFPeer reviewe

Disambiguating past events: accurate source memory for time and context depends on different retrieval processes

Participant payment was provided by the School of Psychology and Neuroscience ResPay scheme.Current animal models of episodic memory are usually based on demonstrating integrated memory for what happened, where it happened, and when an event took place. These models aim to capture the testable features of the definition of human episodic memory which stresses the temporal component of the memory as a unique piece of source information that allows us to disambiguate one memory from another. Recently though, it has been suggested that a more accurate model of human episodic memory would include contextual rather than temporal source information, as humans’ memory for time is relatively poor. Here, two experiments were carried out investigating human memory for temporal and contextual source information, along with the underlying dual process retrieval processes, using an immersive virtual environment paired with a ‘Remember-Know’ memory task. Experiment 1 (n = 28) showed that contextual information could only be retrieved accurately using recollection, while temporal information could be retrieved using either recollection or familiarity. Experiment 2 (n = 24), which used a more difficult task, resulting in reduced item recognition rates and therefore less potential for contamination by ceiling effects, replicated the pattern of results from Experiment 1. Dual process theory predicts that it should only be possible to retrieve source context from an event using recollection, and our results are consistent with this prediction. That temporal information can be retrieved using familiarity alone suggests that it may be incorrect to view temporal context as analogous to other typically used source contexts. This latter finding supports the alternative proposal that time since presentation may simply be reflected in the strength of memory trace at retrieval – a measure ideally suited to trace strength interrogation using familiarity, as is typically conceptualised within the dual process framework.PostprintPeer reviewe

Distance- rather than location-based temporal judgements are more accurate during episodic recall in a real-world task

Definitions of episodic memory typically emphasise the importance of spatiotemporal frameworks in the contextual reconstruction of episodic retrieval. However, our ability to retrieve specific temporal contexts of experienced episodes is poor. This has bearing on the prominence of temporal context in the definition and evaluation of episodic memory, particularly among non-human animals. Studies demonstrating that rats rely on elapsed time (distance) rather than specific timestamps (location) to disambiguate events have been used to suggest that human episodic memory is qualitatively different to other species. We examined whether humans were more accurate using a distance- or location-based method for judging when an event happened. Participants (n = 57) were exposed to a series of events and then asked either when (e.g., 1:03 pm) or how long ago (HLA; e.g., 33 min) a specific event took place. HLA judgements were significantly more accurate, particularly for the most recently experienced episode. Additionally, a significantly higher proportion of participants making HLA judgements accurately recalled non-temporal episodic features across all episodes. Finally, for participants given the choice of methods for making temporal judgements, a significantly higher proportion chose to use HLA judgements. These findings suggest that human and non-human temporal judgements are not qualitatively different.PostprintPeer reviewe

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

The hippocampus encodes both spatial and nonspatial aspects of a rat's 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

Lateral entorhinal cortex lesions impair both egocentric and allocentric object-place associations

This work was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grant BB/I019367/1.During navigation, landmark processing is critical either for generating an allocentric-based cognitive map or in facilitating egocentric-based strategies. Increasing evidence from manipulation and single-unit recording studies has highlighted the role of the entorhinal cortex in processing landmarks. In particular, the lateral (LEC) and medial (MEC) sub-regions of the entorhinal cortex have been shown to attend to proximal and distal landmarks, respectively. Recent studies have identified a further dissociation in cue processing between the LEC and MEC based on spatial frames of reference. Neurons in the LEC preferentially encode egocentric cues while those in the MEC encode allocentric cues. In this study, we assessed the impact of disrupting the LEC on landmark-based spatial memory in both egocentric and allocentric reference frames. Animals that received excitotoxic lesions of the LEC were significantly impaired, relative to controls, on both egocentric and allocentric versions of an object–place association task. Notably, LEC lesioned animals performed at chance on the egocentric version but above chance on the allocentric version. There was no significant difference in performance between the two groups on an object recognition and spatial T-maze task. Taken together, these results indicate that the LEC plays a role in feature integration more broadly and in specifically processing spatial information within an egocentric reference frame.Publisher PDFPeer reviewe

Fan Cells in Layer 2 of the Lateral Entorhinal Cortex Are Critical for Episodic-like Memory

This work was supported by a Carnegie Trust Collaborative Research Grant to J.A. and M.F.N, a Henry Dryerre scholarship from the Royal Society of Edinburgh to B.V., and grants from Wellcome Trust (200855/Z/16/Z) to M.F.N, and BBSRC (BB/M025454/1) to M.F.N.Episodic memory requires different types of information to be bound together to generate representations of experiences. The lateral entorhinal cortex (LEC) and hippocampus are required for episodic-like memory in rodents [1, 2]. The LEC is critical for integrating spatial and contextual information about objects [2, 3, 4, 5, 6]. Further, LEC neurons encode objects in the environment and the locations where objects were previously experienced and generate representations of time during the encoding and retrieval of episodes [7, 8, 9, 10, 11, 12]. However, it remains unclear how specific populations of cells within the LEC contribute to the integration of episodic memory components. Layer 2 (L2) of LEC manifests early pathology in Alzheimer’s disease (AD) and related animal models [13, 14, 15, 16]. Projections to the hippocampus from L2 of LEC arise from fan cells in a superficial sub-layer (L2a) that are immunoreactive for reelin and project to the dentate gyrus [17, 18]. Here, we establish an approach for selectively targeting fan cells using Sim1:Cre mice. Whereas complete lesions of the LEC were previously found to abolish associative recognition memory [2, 3], we report that, after selective suppression of synaptic output from fan cells, mice can discriminate novel object-context configurations but are impaired in recognition of novel object-place-context associations. Our results suggest that memory functions are segregated between distinct LEC networks.Publisher PDFPeer reviewe

Lateral entorhinal cortex lesions impair odor-context associative memory in male rats

This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M010996/1].Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information. The current study tests whether the role of LEC in integrating information extends to long-term multimodal item-context associations. In Experiment 1, male rats were trained on a context-dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor-context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long-term odor-context associative memory.Publisher PDFPeer reviewe

I TO JE MATEMATIKA - DOMAĆA ZADAĆA U TROGODIŠNJOJ STRUKOVNOJ ŠKOLI

KLD was funded by a Bobby Jones scholarship and by the University of St Andrews.Imagining the future is a powerful tool for making plans and solving problems. It is thought to rely on the episodic system which also underpins remembering a specific past event [1, 2, 3]. However, the emergence of episodic future thinking over development and evolution is debated [4, 5, 6, 7, 8, 9]. One key source of positive evidence in pre-schoolers and animals is the “spoon test” or item choice test [4, 10], in which participants encounter a problem in one context and then a choice of items in another context, one of which is the solution to the problem. A majority of studies report that most children choose the right item by age 4 [10, 11, 12, 13, 14, 15, cf. 16]. Apes and corvids have also been shown to pass versions of the test [17, 18, 19]. However, it has been suggested that a simpler mechanism could be driving choice: the participant simply chooses the item that has been assigned salience or value, without necessarily imagining the future event [16, 20, 21, 22, 23]. We developed a new test in which two of the items offered to children were associated with positive outcomes, but only one was still useful. We found that older children (5-, 6-, and 7-year-olds) chose the correct item at above chance levels, but younger children (3- and 4-year-olds) did not. In further tests, 4-year-olds showed an intact memory for the encoding event. We conclude that positive association substantially impacts performance on item choice tests in 4-year-olds and that future planning may have a more protracted developmental trajectory than episodic memory.PostprintPeer reviewe