Temporally selective contextual encoding in the dentate gyrus of the hippocampus

Rangel, Lara M.; Alexander, Andrew S.; Aimone, James B.; Wiles, Janet; Gage, Fred H.; Chiba, Andrea A.; Quinn, Laleh K.

doi:10.1038/ncomms4181

Cited by 90 publications

(72 citation statements)

References 31 publications

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“…This conjecture would be consistent with evidence that granule cells become progressively less important for the discrimination of similar contexts as they mature [19], as well as computational [20] and experimental [21] evidence that newborn neurons may encode events that occur in close proximity to each other on the scale of weeks in a common population of granule cells. Although this model operates on a shorter timescale, it does generate a testable hypothesis-that events that co-occur within weeks of each other will be encoded differently in the granule cell population (likely with more orthogonal recruitment patterns) if they are reliably experienced on the same day, within the timescale of sustained Arc transcription (i.e., <8 h).…”

Section: Discussionsupporting

confidence: 66%

Sustained Arc expression in adult-generated granule cells

Meconi

Lui

Marrone

2015

Neuroscience Letters

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Section: Discussionsupporting

confidence: 66%

Sustained Arc expression in adult-generated granule cells

Meconi

Lui

Marrone

2015

Neuroscience Letters

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“…Although experimental evidence supporting a role for encoding uncertainty or unpredictability of threats is currently lacking, a recent study found using in vivo recordings of place cells in the DG that levels of adult hippocampal neurogenesis influence encoding of temporally separated exposures to a context in non-overlapping ensembles of DGCs (Rangel et al, 2014). It is plausible that such a mechanism may minimize interference between cues associated with predictable and unpredictable contingencies to govern adaptive fear responses to uncertain threats.…”

Section: Resolution Of Conflicting Contingencies and Goalsmentioning

confidence: 98%

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Besnard

Sahay

2015

Neuropsychopharmacol

186

159

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The generalization of fear is an adaptive, behavioral, and physiological response to the likelihood of threat in the environment. In contrast, the overgeneralization of fear, a cardinal feature of posttraumatic stress disorder (PTSD), manifests as inappropriate, uncontrollable expression of fear in neutral and safe environments. Overgeneralization of fear stems from impaired discrimination of safe from aversive environments or discernment of unlikely threats from those that are highly probable. In addition, the time-dependent erosion of episodic details of traumatic memories might contribute to their generalization. Understanding the neural mechanisms underlying the overgeneralization of fear will guide development of novel therapeutic strategies to combat PTSD. Here, we conceptualize generalization of fear in terms of resolution of interference between similar memories. We propose a role for a fundamental encoding mechanism, pattern separation, in the dentate gyrus (DG)-CA3 circuit in resolving interference between ambiguous or uncertain threats and in preserving episodic content of remote aversive memories in hippocampal-cortical networks. We invoke cellular-, circuit-, and systems-based mechanisms by which adult-born dentate granule cells (DGCs) modulate pattern separation to influence resolution of interference and maintain precision of remote aversive memories. We discuss evidence for how these mechanisms are affected by stress, a risk factor for PTSD, to increase memory interference and decrease precision. Using this scaffold we ideate strategies to curb overgeneralization of fear in PTSD.

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“…It is well accepted that the impact of DA in other regions can be considered as temporal in nature, providing capabilities in reinforcement learning and consolidation. Likewise, we have previously hypothesized that the DG's population activity would exhibit strong temporal structure because of its mixed population of young and old GCs (33,34), a prediction that has been observed in a series of behavioral and physiology studies (35,36). We accordingly predicted that the suppression of DG activity after DA may interact nontrivially with these temporal associations produced by the DG.…”

Section: Chr2 In the Lcmentioning

confidence: 99%

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

Deng

Aimone

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.T he brain structures crucial for memory formation are presumably under the control of the midbrain dopamine (DA) system, which selectively marks experiences that lead to reward (1, 2). In the striatum and the cortex, repetitive pairing of DA input after, but not before, sensorimotor stimulus within a narrow time window promotes structural and functional connectivity (3, 4), which may provide a cellular basis for reward to reinforce specifically an immediate past action. In the hippocampus, a structure that is instrumental in forming memories of contexts and objects making up the experiences (5, 6), DA must be present at the induction of long-term potentiation (LTP) to increase the magnitude of early-and late-phase LTP (7-10). When released during learning, DA also has been found to enhance the reactivation of newly formed neural ensembles (11). The requisite coincidence between the DA signal and the conditioning stimulation may serve to ensure that only inputs concurrent with or occurring shortly before reward are encoded in long-term memory. However, rewarding outcomes often may be delayed, and the involvement of the hippocampus is necessary when an event and its outcome are temporally discontinuous (12). This type of "memory" can be formed rapidly after even a single experience (5,6), and behavioral studies demonstrate that application of DA agonists in the hippocampus hours after training promotes memory maintenance (13,14), indicating that DA released from midbrain projections (Fig. S1) exerts distinct influences on the hippocampus to reinforce memory of earlier events selectively.Here we surveyed the dentate gyrus (DG) of the hippocampus to explore the possible sites and actions of DA. As the first stage of the intrahippocampal trisynaptic loop, the DG receives multiple processed sensory inputs from the entorhinal cortex (EC) and uses conjunctive encoding to integrate them for a memory representation (15). This region, together with area ...

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Temporally selective contextual encoding in the dentate gyrus of the hippocampus

Cited by 90 publications

References 31 publications

Sustained Arc expression in adult-generated granule cells

Sustained Arc expression in adult-generated granule cells

Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

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