Hippocampal Neurogenesis Regulates Forgetting


Science 9 May 2014:  Vol. 344  no. 6184  pp. 598-602

Hippocampal Neurogenesis Regulates Forgetting During Adulthood and Infancy

Katherine G. Akers, et.al.

Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, M5G 1X8, Canada.

Institute of Medical Science, University of Toronto, Toronto, M5S 1A8, Canada.

Department of Physiology, University of Toronto, Toronto, M5S 1A8, Canada.

Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.

Department of Psychology, University of Toronto, Toronto, M5S 3GM, Canada.


Throughout life, new neurons are continuously added to the dentate gyrus. As this continuous addition remodels hippocampal circuits, computational models predict that neurogenesis leads to degradation or forgetting of established memories. Consistent with this, increasing neurogenesis after the formation of a memory was sufficient to induce forgetting in adult mice. By contrast, during infancy, when hippocampal neurogenesis levels are high and freshly generated memories tend to be rapidly forgotten (infantile amnesia), decreasing neurogenesis after memory formation mitigated forgetting. In precocial species, including guinea pigs and degus, most granule cells are generated prenatally. Consistent with reduced levels of postnatal hippocampal neurogenesis, infant guinea pigs and degus did not exhibit forgetting. However, increasing neurogenesis after memory formation induced infantile amnesia in these species.

In both artificial systems and brain networks there is a trade-off between plasticity—the ability to incorporate new information—and stability—ensuring that the process of incorporating new information does not degrade information already stored in that network. In the hippocampus, new neurons continue to be generated in the subgranular zone of the dentate gyrus (DG) beyond development and into adulthood. These new neurons synaptically integrate into hippocampal circuits and provide potential substrates for new learning. Promoting the production of new neurons in adult mice facilitates the formation of new hippocampal memories. However, the continuous integration of new neurons may affect memories already stored in these circuits. As new neurons integrate into the hippocampus, they compete with existing cells for inputs and outputs, establishing new synaptic connections that may coexist with, or even replace, older synaptic connections. As such remodeling necessarily alters the configuration of DG-CA3 circuits and likely rescales synaptic weights of preexisting connections, computational models predict that high levels of hippocampal neurogenesis will lead to forgetting of information already stored in those circuits.

Although hippocampal neurogenesis persists throughout life, rates decline dramatically with age. Therefore, this predicted remodeling-induced forgetting should be most pronounced during infancy, when hippocampal neurogenesis is high. Consistent with this, infantile forgetting [or infantile amnesia] is observed across a wide range of species, including humans. Neurobiological accounts of infantile amnesia previously emphasized that continued brain maturation might interfere with consolidation and/or storage of infant memories, rendering them inaccessible at later time points. Here, we test whether postnatal hippocampal neurogenesis, in particular, modulates ontogenetic changes in memory persistence.

The hippocampus encodes memories for places and events. The observation that hippocampal neurogenesis persists into adulthood led to the idea that neurogenesis modulates hippocampal memory function. To our knowledge, all previous studies examining the relationship between hippocampal neurogenesis and memory have used essentially the same design; they manipulated hippocampal neurogenesis before training and examined the impact of this manipulation on subsequent memory formation (i.e., they investigated the anterograde effects of manipulating neurogenesis on memory). The view that emerged from these studies is that, once sufficiently mature, new neurons positively contribute to encoding of new hippocampus-dependent memories, perhaps by providing new substrates for memory storage. Here, we examined the retrograde impact of similar manipulations of neurogenesis on memory. Through a series of studies, we showed that high levels of neurogenesis disrupt established hippocampus-dependent memories. As such, our findings reveal a novel role for neurogenesis in forgetting or memory clearance, in line with theoretical predictions.

The hippocampus is thought to rapidly and automatically encode experiences. Because not all experiences are ultimately remembered, it is likely that forgetting processes continuously degrade or clear stored information from the hippocampus. Our results identify neurogenesis as one such process that promotes degradation of hippocampus-dependent memories, most likely by reconfiguring DG-CA3 circuits. Successful memory retrieval may result from the reactivation of patterns of neural activity present at the time of memory encoding (i.e., pattern completion). Because neurogenesis reconfigures hippocampal circuits, this may reduce the ability of a given set of cues (or inputs) to reinvoke the same pattern of activity (i.e., pattern completion failure). During infancy, when neurogenesis levels are elevated, high rates of decay render hippocampus-dependent memories [that are declarative in nature] inaccessible at later time points. Reducing neurogenesis at this developmental stage can increase the persistence of hippocampus-dependent memories. During adulthood, when neurogenesis levels are lower,    memories are more resistant to decay. Artificially increasing neurogenesis after learning, however, may be sufficient to induce forgetting.



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