Memory Time

Department of Neuroscience, Mount Sinai School of Medicine, New York, NY 10029, USA.
Neuron (Impact Factor: 15.05). 08/2011; 71(4):571-3. DOI: 10.1016/j.neuron.2011.08.006
Source: PubMed


In this issue of Neuron, MacDonald et al. describe hippocampal "time cells" that fire during specific delay periods as rats performed a memory task. Converging results in monkeys suggest that the hippocampus encodes episodes by signaling events in time.

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    • "Young CA3 place cells readily remap and shift their representations, while aged CA3 place cells retain their original fields despite changes in the environment (Wilson et al. 2006; Yassa et al. 2011). Next to place cells in the hippocampal CA1 and CA3 subregions, time cells have recently been identified, shown to track the elapsing of time (Macdonald et al. 2011; Shapiro 2011; Mankin et al. 2012). Given our data, it is tempting to speculate that such time cells participate in TPL memory networks and undergo similar rigidity with aging. "
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    ABSTRACT: Time-place learning (TPL) offers the possibility to study the functional interaction between cognition and the circadian system with aging. With TPL, animals link biological significant events with the location and the time of day. This what-where-when type of memory provides animals with an experience-based daily schedule. Mice were tested for TPL five times throughout their lifespan and showed (re)learning from below chance level at the age of 4, 7, 12, and 18 mo. In contrast, at the age of 22 mo these mice showed preservation of TPL memory (absence of memory loss), together with deficiencies in the ability to update time-of-day information. Conversely, the majority of untrained (naïve) mice at 17 mo of age were unable to acquire TPL, indicating that training had delayed TPL deficiencies in the mice trained over lifespan. Two out of seven naïve mice, however, compensated for correct performance loss by adapting an alternative learning strategy that is independent of the age-deteriorating circadian system and presumably less cognitively demanding. Together, these data show the age-sensitivity of TPL, and the positive effects of repeated training over a lifetime. In addition, these data shed new light on aging-related loss of behavioral flexibility to update time-of-day information. © 2015 Mulder et al.; Published by Cold Spring Harbor Laboratory Press.
    Learning & memory (Cold Spring Harbor, N.Y.) 05/2015; 22(5):278-288. DOI:10.1101/lm.037440 · 3.66 Impact Factor
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    • "Clock genes are expressed in all sub regions of the hippocampus and thought to support temporally regulated events underlying memory processes, such as acquisition, consolidation and retrieval (Eckel-Mahan & Storm, 2009; Gerstner & Yin, 2010; Gerstner et al., 2009; Jilg et al., 2010; Kondratova et al., 2010; Rawashdeh & Stehle, 2010). Recent findings suggest that hippocampal ''time cells'' in the CA1 region take part in episodic memory networks and include a code that can be used to distinguish time intervals on an extended scale of hours to days (Mankin et al., 2012; Shapiro, 2011; Yin & Troger, 2011). Therefore, experience-related cues may act as zeitgebers to a distributed network of cTPL involved brain regions, including the hippocampus, where local timekeeping mechanisms may be entrained. "
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    ABSTRACT: During Time-Place Learning (TPL), animals link biological significant events (e.g. encountering predators, food, mates) with the location and time of occurrence in the environment. This allows animals to anticipate which locations to visit or avoid based on previous experience and knowledge of the current time of day. The TPL task applied in this study consists of three daily sessions in a three-arm maze, with a food reward at the end of each arm. During each session, mice should avoid one specific arm to avoid a foot-shock. We previously demonstrated that, rather than using external cue-based strategies, mice use an internal clock (circadian strategy) for TPL, referred to as circadian TPL (cTPL). It is unknown in which brain region(s) or peripheral organ(s) the consulted clock underlying cTPL resides. Three candidates were examined in this study: (a) the suprachiasmatic nucleus (SCN), a light entrainable oscillator (LEO) and considered the master circadian clock in the brain, (b) the food entrainable oscillator (FEO), entrained by restricted food availability, and (c) the adrenal glands, harboring an important peripheral oscillator. cTPL performance should be affected if the underlying oscillator system is abruptly phase-shifted. Therefore, we first investigated cTPL sensitivity to abrupt light and food shifts. Next we investigated cTPL in SCN-lesioned- and adrenalectomized mice. Abrupt FEO phase-shifts (induced by advancing and delaying feeding time) affected TPL performance in specific test sessions while a LEO phase-shift (induced by a light pulse) more severely affected TPL performance in all three daily test sessions. SCN-lesioned mice showed no TPL deficiencies compared to SHAM-lesioned mice. Moreover, both SHAM- and SCN-lesioned mice showed unaffected cTPL performance when re-tested after bilateral adrenalectomy. We conclude that, although cTPL is sensitive to timing manipulations with light as well as food, neither the SCN nor the adrenals are required for cTPL in mice.
    Chronobiology International 08/2014; 31(9):1-18. DOI:10.3109/07420528.2014.944975 · 3.34 Impact Factor
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    • "Indeed, BMAL1 is negatively regulated by MAPK (Sanada et al., 2002), providing a molecular clock resetting mechanism by training. Interestingly, next to “place” cells in the hippocampal CA1 and CA3 region, “time” cells have recently been identified and shown to track the elapsing of an interval (Macdonald et al., 2011; Shapiro, 2011). It is likely that this hippocampal clock may not only be entrained by training (event encounters), but is also modulated by internal cues like SCN and FEO outputs. "
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    ABSTRACT: Time-Place learning (TPL) refers to the ability of animals to remember important events that vary in both time and place. This ability is thought to be functional to optimize resource localization and predator avoidance in a circadian changing environment. Various studies have indicated that animals use their circadian system for TPL. However, not much is known about this specific role of the circadian system in cognition. This review aims to put TPL in a broader context and to provide an overview of historical background, functional aspects, and future perspectives of TPL. Recent advances have increased our knowledge on establishing TPL in a laboratory setting, leading to the development of a behavioral paradigm demonstrating the circadian nature of TPL in mice. This has enabled the investigation of circadian clock components on a functional behavioral level. Circadian TPL (cTPL) was found to be Cry clock gene dependent, confirming the essential role of Cry genes in circadian rhythms. In contrast, preliminary results have shown that cTPL is independent of Per genes. Circadian system decline with aging predicts that cTPL is age sensitive, potentially qualifying TPL as a functional model for episodic memory and aging. The underlying neurobiological mechanism of TPL awaits further examination. Here we discuss some putative mechanisms.
    Frontiers in Molecular Neuroscience 04/2013; 6:8. DOI:10.3389/fnmol.2013.00008 · 4.08 Impact Factor
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