Opinion
Remote Memory and the Hippocampus: A Constructive Critique

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Highlights

It is widely agreed the hippocampus plays a crucial role in memory encoding.

The question of how long a hippocampal trace is required to retrieve a memory is unresolved.

Opposing theoretical accounts advocate either the hippocampus is unnecessary for memory retrieval in the longer term or that is it required in perpetuity. There is evidence from animal and human work to support both views; consequently, extant theories cannot account for these conflicting findings.

We suggest that the hippocampal role in memory retrieval is not simply a question of persistence, but is best characterised as a functional shift over time from retention to reconstruction of the past in the absence of the original trace.

This new perspective accounts for existing data and offers a means to leverage a clearer understanding of the hippocampal-neocortical interactions that support memory retrieval.

The hippocampus is known to be recruited during the recall of experiences from our distant past, despite evidence that memory traces in this region vanish over time. Extant theories of systems-level consolidation have yet to accommodate both phenomena. We propose that the hippocampus reconstructs remote memories in the absence of the original trace. It accomplishes this by assembling consolidated neocortical elements into spatially coherent scenes that form the basis of unfolding memory events. This reconstruction is likely facilitated by input from the ventromedial prefrontal cortex. This process-oriented approach to hippocampal recruitment during remote recollection is consistent with its increasingly acknowledged role in constructing mental representations beyond the domain of memory.

Section snippets

A Divergent Debate on Hippocampal-Dependent Memory

Hippocampal damage impairs the formation and recall of recent memories in humans [1], non-human primates [2], and rodents [3]. However, conflicting evidence regarding its necessity for remote memory retrieval has generated two opposing perspectives. There is cross-species evidence of temporally graded retrograde amnesia (see Glossary), the preservation of older memories following hippocampal damage 4, 5, 6. This reinforces the view of the standard consolidation theory that memories are stored

The Evanescent Hippocampal Engram

Theoretical accounts of how memory traces are stored within the hippocampus have been motivated both by its architecture and neural activity. Initial input to the hippocampal circuit generates sparse activity in the dentate gyrus, assumed to reduce interference between similar memories. These distinct patterns are conveyed to CA3, where intrinsic recurrent connections are thought to form a complete memory trace. The resultant output produces a sparse pattern in CA1, and this unique

A Consensus on Consolidation

Systems-level consolidation is a hypothesised time-dependent process of hippocampal-facilitated strengthening of neocortical neural connections post-learning 64, 65. Supporting evidence in humans arises from hippocampal [66] and neocortical [67] reinstatement of activity patterns present at encoding during subsequent quiescence and sleep. This regional activity is synchronised [68], with bursts of hippocampal activity being entrained by slower oscillations in the neocortex [69]. Memory replay

Reconstruction of the Past by the Hippocampus

Hippocampal damage in humans can impair the recollection of specific autobiographical memories from any period of life before the damage occurred 8, 9 (Figure 2C), and neuroimaging studies in healthy individuals reveal hippocampal engagement during the recollection of both recent and remote autobiographical memories [95]. This implies that no duration of systems-level consolidation will relieve the hippocampus of a role in retrieval. Likewise, hippocampal lesions in rodents yield a flat

The Remote Control of Memory

Time-dependent strengthening of connectivity between neocortical modules is thought to form the basis of systems-level consolidation. The medial prefrontal cortex becomes an increasingly important hub during this process, with lesions selectively disrupting remote memories in animals [131]. Likewise, in humans, memory-specific activity patterns emerge in the ventromedial prefrontal cortex (vmPFC) over the course of consolidation 93, 94, 132 while vmPFC damage impairs autobiographical memory

Concluding Remarks and Future Perspectives

A proliferation of evidence challenges the notion of permanent hippocampal memory traces. Core assumptions underlying extant perspectives on systems-level consolidation and the fundamental role of the hippocampus may need to be reassessed. The hippocampus is unlikely to be a permanent indexer of memories. Given the extraordinary demands placed upon the hippocampus for continuous encoding of experience, and the required representational flexibility involved in imagination and future-thinking,

Acknowledgements

The authors are supported by a Wellcome Principal Fellowship to E.A.M. (210567/Z/18/Z).

Glossary

Consolidation
the strengthening of neuronal connections on both a cellular and a network level, manifesting as the successful subsequent retention of learned information.
Delta waves
low-frequency (1–4-Hz) synchronised neural activity that is prevalent during sleep.
Episodic/autobiographical memory
the multisensory mental reconstruction of a personally experienced past event from a particular place and time.
Long-term potentiation/depression
the persistent strengthening or weakening of postsynaptic

References (150)

  • Y. Jeantet et al.

    Evolution of hippocampal spatial representation over time in mice

    Neurobiol. Learn. Mem.

    (2012)
  • L.T. Thompson et al.

    Long-term stability of the place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats

    Brain Res.

    (1990)
  • A.J. Hill

    First occurrence of hippocampal spatial firing in a new environment

    Exp. Neurol.

    (1978)
  • K.K. Tayler

    Reactivation of neural ensembles during the retrieval of recent and remote memory

    Curr. Biol.

    (2013)
  • K.Z. Tanaka

    Cortical representations are reinstated by the hippocampus during memory retrieval

    Neuron

    (2014)
  • C.A. Denny

    Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis

    Neuron

    (2014)
  • I. Goshen

    Dynamics of retrieval strategies for remote memories

    Cell

    (2011)
  • S. Ge

    A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain

    Neuron

    (2007)
  • N.B. Danielson

    Distinct contribution of adult-born hippocampal granule cells to context encoding

    Neuron

    (2016)
  • P. Ambrogini

    Spatial learning affects immature granule cell survival in adult rat dentate gyrus

    Neurosci. Lett.

    (2000)
  • H. Eichenbaum

    Memory on time

    Trends Cogn. Sci.

    (2013)
  • L.D. de Voogd

    Awake reactivation of emotional memory traces through hippocampal-neocortical interactions

    NeuroImage

    (2016)
  • T.J. Davidson

    Hippocampal replay of extended experience

    Neuron

    (2009)
  • S. Groch

    Dissociating the contributions of slow-wave sleep and rapid eye movement sleep to emotional item and source memory

    Neurobiol. Learn. Mem.

    (2015)
  • C.M. Wierzynski

    State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep

    Neuron

    (2009)
  • H.M. Bonnici et al.

    Two years later – revisiting autobiographical memory representations in vmPFC and hippocampus

    Neuropsychologia

    (2018)
  • N.J. Broadbent et al.

    Remote context fear conditioning remains hippocampus-dependent irrespective of training protocol, training-surgery interval, lesion size, and lesion method

    Neurobiol. Learn. Mem.

    (2013)
  • D. Kwan

    Deficits in past remembering extend to future imagining in a case of developmental amnesia

    Neuropsychologia

    (2010)
  • H.J. Spiers

    Hippocampal amnesia

    Neurocase

    (2001)
  • P.A. Forcelli

    Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys

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

    (2014)
  • S.M. Zola-Morgan et al.

    The primate hippocampal formation: evidence for a time-limited role in memory storage

    Science

    (1990)
  • J.J. Kim et al.

    Modality-specific retrograde amnesia of fear

    Science

    (1992)
  • P.J. Bayley

    The fate of old memories after medial temporal lobe damage

    J. Neurosci.

    (2006)
  • L.R. Squire

    Memory consolidation

    Cold Spring Harb. Perspect. Biol.

    (2015)
  • L. Nadel

    Systems consolidation and hippocampus: two views

    Debates Neurosci.

    (2007)
  • M. Moscovitch

    Episodic memory and beyond: the hippocampus and neocortex in transformation

    Annu. Rev. Psychol.

    (2016)
  • D.L. Schacter et al.

    The cognitive neuroscience of constructive memory: remembering the past and imagining the future

    Philos. Trans. R. Soc. Lond. B. Biol. Sci.

    (2007)
  • H. Eichenbaum

    Prefrontal-hippocampal interactions in episodic memory

    Nat. Rev. Neurosci.

    (2017)
  • A. Attardo

    Impermanence of dendritic spines in live adult CA1 hippocampus

    Nature

    (2015)
  • R.C. O’Reilly

    Complementary learning systems

    Cogn. Sci.

    (2014)
  • S. Li

    Dopamine-dependent facilitation of LTP induction in hippocampal CA1 by exposure to spatial novelty

    Nat. Neurosci.

    (2003)
  • A. Kemp et al.

    The hippocampal CA1 region and dentate gyrus differentiate between environmental and spatial feature encoding through long-term depression

    Cereb. Cortex

    (2008)
  • K. Nakao

    Hippocampal long-term depression as an index of spatial working memory

    Eur. J. Neurosci.

    (2002)
  • W.C. Abraham

    Induction and experience-dependent consolidation of stable long-term potentiation lasting months in the hippocampus

    J. Neurosci.

    (2002)
  • G.I. Irvine

    Enriched environment exposure regulates excitability, synaptic transmission, and LTP in the dentate gyrus of freely moving rats

    Hippocampus

    (2006)
  • A.D. Ekstrom

    Cellular networks underlying human spatial navigation

    Nature

    (2003)
  • C. Kentros

    Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade

    Science

    (1998)
  • S. Renaudineau

    Impaired long-term stability of CA1 place cell representation in mice lacking the transcription factor zif268/egr1

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

    (2009)
  • J.F. Miller

    Neural activity in human hippocampal formation reveals the spatial context of retrieved memories

    Science

    (2013)
  • Y. Ziv

    Long-term dynamics of CA1 hippocampal place codes

    Nat. Neurosci.

    (2013)
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