Trends in Neurosciences
Volume 36, Issue 9, September 2013, Pages 497-503
Journal home page for Trends in Neurosciences

Opinion
Hippocampal neurogenesis and forgetting

https://doi.org/10.1016/j.tins.2013.05.002Get rights and content

Highlights

  • Previous data examined the anterograde impact of hippocampal neurogenesis on memory.

  • We propose a novel yet complementary retrograde role for neurogenesis in forgetting.

  • Continued integration of new neurons disrupts patterns of previously stored information.

The hippocampus is thought to automatically encode all experience, yet the vast majority of our experiences are not remembered later. Although psychological theories have postulated the existence of decay processes for declarative memory, the corresponding neurobiological mechanisms are unknown. Here we develop the hypothesis that ongoing hippocampal neurogenesis represents a decay process that continually clears memories from the hippocampus. As newborn granule cells integrate into established hippocampal circuits, they form new input and output connections over the course of several weeks. Because successful memory retrieval relies on reinvoking patterns of activity that occurred at the time of encoding (pattern completion), neurogenesis-induced remodeling of hippocampal circuits incrementally reduces the likelihood that a given retrieval cue will reinvoke a previously stored pattern.

Introduction

In the 1960s Altman published pioneering studies showing that neurogenesis persists in the subgranular zone of the hippocampus beyond development and into adulthood 1, 2, 3. Although this field largely lay dormant for the better part of the next three decades, interest was rekindled in the 1990s when new immunohistochemical methods were developed that made it possible to definitively label newborn granule cells [4]. This prompted an explosion of studies asking whether and how new neurons contribute to hippocampal memory formation. These studies have taken advantage of increasingly sophisticated methods for ablating 5, 6, 7 or, more recently, disrupting the activity 8, 9 of new neurons, with the general premise of these studies being that new neurons are in some way ‘good’ for hippocampal memory. Accordingly, there is now an extensive (but sometimes messy) body of literature examining the impact of both increasing and decreasing adult neurogenesis on the formation of new hippocampal memories [10]. By contrast, here we consider the impact of ongoing neurogenesis on existing memories and propose a novel role for neurogenesis in forgetting.

Section snippets

New neurons and new memories

It is surprising that, almost without exception, previous studies have used essentially the same experimental design to examine the role of new neurons in memory. Neurogenesis levels are usually manipulated in adult rodents, and then, days or weeks later, the ability to form new hippocampus-dependent memories is evaluated. The typical result from these studies is that reducing neurogenesis impairs subsequent hippocampal memory formation. Conversely, increasing neurogenesis facilitates

New neurons and old memories

This focus on the anterograde effects of manipulating adult neurogenesis on memory has come at the expense of an examination of potential retrograde effects: how does the integration of new neurons into existing hippocampal circuits impact information already stored in those circuits? The integration of newborn neurons into the hippocampus follows a stereotypical course [31]. Division of progenitor cells in the subgranular zone gives rise to new cells that migrate into the innermost part of the

New neurons and forgetting

Successful memory retrieval requires intact encoding, consolidation, and retrieval. Some instances of memory failure are simply due to ineffective encoding (such as not attending to where one puts one's glasses; a type of memory failure common during multitasking). However, as Tulving emphasized, forgetting is ‘the inability to recall something now that could be recalled on an earlier occasion’ [54]. More precisely, forgetting may be defined as the inability to access information that was (i)

Types of forgetting

Although forgetting has received scant attention in neurobiological studies of memory (for some notable exceptions, see 61, 62, 63, 64), within the traditions of experimental psychology, forgetting has received significantly more consideration.

The most common form of forgetting studied in the psychological laboratory (although probably not the most common form of forgetting in daily life) is a type of retrieval-induced forgetting known as cue overload [65]. As stated above, successful memory

Neurogenesis and nonspecific retroactive interference

We propose that ongoing neurogenesis represents an additional distinct form of forgetting that also depends on nonspecific retroactive interference. Similar to the modification of existing synaptic connections produced by the formation of new memories, the integration of new neurons into hippocampal circuits adds new and modifies existing synaptic connections. The consequence of this structural interference is that the circuitry of the hippocampus is continuously evolving, and so the likelihood

Forgetting versus consolidation

Although much of what we experience is ultimately forgotten, memories for some events persist. In the face of continuous neurogenesis-dependent decay, how might some memories survive? In our proposal, the fate of any memory depends on the outcome of a competition between two opposing processes: memory trace consolidation (i.e., the cellular and systems processes that promote stabilization of traces within hippocampal and extra-hippocampal circuits 72, 73, 74, 75, 76) and memory trace decay

Summary and predictions

Previous studies have examined the impact of manipulating levels of hippocampal neurogenesis on future memory formation. By contrast, here we focused on how the integration of newborn neurons into hippocampal circuits impacts existing memories, and therefore provided a new perspective on how ongoing neurogenesis impacts hippocampal memory function. We propose that ongoing neurogenesis produces an unrelenting form of retroactive interference that is indifferent to memory content. This

Acknowledgments

This project was supported by Canadian Institutes of Health Research (CIHR) grants to P.W.F. (MOP-86762), S.K. (MOP-93644), and S.A.J. (MOP-74650) and by a ‘Chase an Idea in Paediatric Neuroscience’ grant from The Centre for Brain and Behaviour at the Hospital for Sick Children. We thank Leonardo Restivo for artwork.

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