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Retrieval-induced forgetting (RIF) refers to the finding that retrieving a memory can impair subsequent recall of related memories. Here, the authors present a new model of how the brain gives rise to RIF in both semantic and episodic memory. The core of the model is a recently developed neural network learning algorithm that leverages regular oscillations in feedback inhibition to strengthen weak parts of target memories and to weaken competing memories. The authors use the model to address several puzzling findings relating to RIF, including why retrieval practice leads to more forgetting than simply presenting the target item, how RIF is affected by the strength of competing memories and the strength of the target (to-be-retrieved) memory, and why RIF sometimes generalizes to independent cues and sometimes does not. For all of these questions, the authors show that the model can account for existing results, and they generate novel predictions regarding boundary conditions on these results.

By having subjects drive a virtual taxicab through a computer-rendered town, we examined how landmark and layout information interact during spatial navigation. Subject-drivers searched for passengers, and then attempted to take the most efficient route to the requested destinations (one of several target stores). Experiment 1 demonstrated that subjects rapidly learn to find direct paths from random pickup locations to target stores. Experiment 2 varied the degree to which landmark and layout cues were preserved across two successively learned towns. When spatial layout was preserved, transfer was low if only target stores were altered, and high if both target stores and surrounding buildings were altered, even though in the latter case all local views were changed. This suggests that subjects can rapidly acquire a survey representation based on the spatial layout of the town and independent of local views, but that subjects will rely on local views when present, and are harmed when associations between previously learned landmarks are disrupted. We propose that spatial navigation reflects a hierarchical system in which either layout or landmark information is sufficient for orienting and wayfinding; however, when these types of cues conflict, landmarks are preferentially used.

Author(s): Arne D. Ekstrom [1]; Michael J. Kahana (corresponding author) [1]; Jeremy B. Caplan [1]; Tony A. Fields [2]; Eve A. Isham [2]; Ehren L. Newman [1]; Itzhak Fried (corresponding [...]

Spatial working memory is important for foraging and navigating the environment. However, its neural underpinnings remain poorly understood. The hippocampus, known for its spatial coding and involvement in spatial memory, is widely understood to be necessary for spatial working memory when retention intervals increase beyond seconds into minutes. Here, we describe new evidence that the dorsal hippocampus is not always necessary for spatial working memory for retention intervals of 8 min. Rats were trained to perform a delayed spatial win shift radial arm maze task with an 8‐min delay between study and test phases. We then tested whether bilateral inactivation of the dorsal hippocampus between the study and test phases impaired behavioral performance at test. Inactivation was achieved through a bilateral infusion of lidocaine. Performance following lidocaine was compared to control trials, in which, sterile phosphate buffered saline (PBS) was infused. Test performance did not differ between the lidocaine and PBS conditions, remaining high in each. To explore the possibility that this insensitivity to inactivation was a result of overtraining, a second cohort of animals received substantially less training prior to the infusions. In this second cohort, lidocaine infusions did significantly impair task performance. These data indicate that successful performance of a spatial win‐shift task on the 8‐arm maze need not always be hippocampally dependent. [ABSTRACT FROM AUTHOR]

ABSTRACT A number of studies have examined the theta-rhythmic modulation of neuronal firing in the hippocampal circuit. For extracellular recordings, this is often done by examining spectral properties of the spike-time autocorrelogram, most significantly, for validating the presence or absence of theta modulation across species. These techniques can show significant rhythmicity for high firing rate, highly rhythmic neurons; however, they are substantially biased by several factors including the peak firing rate of the neuron, the amount of time spent in the neuron's receptive field, and other temporal properties of the rhythmicity such as cycle-skipping. These limitations make it difficult to examine rhythmic modulation in neurons with low firing rates or when an animal has short dwell times within the firing field and difficult to compare rhythmicity under disparate experimental conditions when these factors frequently differ. Here, we describe in detail the challenges that researchers face when using these techniques and apply our findings to recent recordings from bat entorhinal grid cells, suggesting that they may have lacked enough data to examine theta rhythmicity robustly. We describe a more sensitive and statistically rigorous method using maximum likelihood estimation (MLE) of a parametric model of the lags within the autocorrelation window, which helps to alleviate some of the problems of traditional methods and was also unable to detect rhythmicity in bat grid cells. Using large batteries of simulated data, we explored the boundaries for which the MLE technique and the theta index can detect rhythmicity. The MLE technique is less sensitive to many features of the autocorrelogram and provides a framework for statistical testing to detect rhythmicity as well as changes in rhythmicity in individual sessions providing a substantial improvement over previous methods. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Large-scale neural activation dynamics in the hippocampal-entorhinal circuit local field potential, observable as theta and gamma rhythms and coupling between these rhythms, is predictive of encoding success. Behavioral studies show that systemic administration of muscarinic acetylcholine receptor antagonists selectively impairs encoding, suggesting that they may also disrupt the coupling between the theta and gamma bands. Here, we tested the hypothesis that muscarinic antagonists selectively disrupt coupling between theta and gamma. Specifically, we characterized the effects of systemically administered scopolamine on movement-induced theta and gamma rhythms recorded in the superficial layers of the medial entorhinal cortex (MEC) of freely moving rats. We report the novel result that gamma power at the peak of theta was most reduced following muscarinic blockade, significantly shifting the phase of maximal gamma power to occur at later phases of theta. We also characterize the existence of multiple distinct gamma bands in the superficial layers of the MEC. Further, we observed that theta frequency was significantly less modulated by movement speed following muscarinic blockade. Finally, the slope relating speed to theta frequency, a correlate of familiarity with a testing enclosure, increased significantly less between the preinjection and recovery trials when scopolamine was administered during the intervening injection session than when saline was administered, suggesting that scopolamine reduced encoding of the testing enclosure. These data are consistent with computational models suggesting that encoding and retrieval occur during the peak and trough of theta, respectively, and support the theory that acetylcholine regulates the balance between encoding versus retrieval. [ABSTRACT FROM AUTHOR]

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimer's disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimer's disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration., Competing Interests: Conflict of Interest Disclosure: No conflicts of interest to disclose.

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state of the brain should change rapidly, or reset, to ensure that the information encountered before and after an event boundary is encoded in different neuronal populations. Norepinephrine (NE) is thought to facilitate this network reorganization. However, it is unknown whether event boundaries drive NE release in the hippocampus and, if so, how NE release relates to changes in hippocampal firing patterns. The advent of the new GRAB NE sensor now allows for the measurement of NE binding with sub-second resolution. Using this tool in mice, we tested whether NE is released into the dorsal hippocampus during event boundaries defined by unexpected transitions between spatial contexts and presentations of novel objections. We found that NE binding dynamics were well explained by the time elapsed after each of these environmental changes, and were not related to conditioned behaviors, exploratory bouts of movement, or reward. Familiarity with a spatial context accelerated the rate in which phasic NE binding decayed to baseline. Knowing when NE is elevated, we tested how hippocampal coding of space differs during these moments. Immediately after context transitions we observed relatively unique patterns of neural spiking which settled into a modal state at a similar rate in which NE returned to baseline. These results are consistent with a model wherein NE release drives hippocampal representations away from a steady-state attractor. We hypothesize that the distinctive neural codes observed after each event boundary may facilitate long-term memory and contribute to the neural basis for the primacy effect., Competing Interests: Declaration of Interests The authors declare no competing interests.

oscillations in the rat hippocampus have been implicated in sensorimotor integration (Bland, 1986), especially during exploratory and wayfinding behavior. We propose that human cortical activity coordinates sensory information with a motor plan to guide wayfinding behavior to known goal locations. To test this hypothesis, we analyzed invasive recordings from epileptic patients while they performed a spatially immersive, virtual taxi driver task. Consistent with this hypothesis, we found oscillations during both exploratory search and goal-seeking behavior and, in particular, during virtual movement, when sensory information and motor planning were both in flux, compared with periods of self-initiated stillness. oscillations had different topographic and spectral characteristics during searching than during goal-seeking, suggesting that different cortical networks exhibit depending on which cognitive functions are driving behavior (spatial learning during exploration vs orienting to a learned representation during goal-seeking). In contrast, oscillations in the beta band appeared to be related to simple motor planning, likely a variant of the Rolandic mu rhythm. These findings suggest that human cortical oscillations act to coordinate sensory and motor brain activity in various brain regions to facilitate exploratory learning and navigational planning.