Regulation of hippocampal memory traces by neurogenesis

Abstract

The hippocampus has long been known as a brain structure fundamental for memory formation and retrieval. Recent technological advances of cellular tracing techniques and optogenetic manipulation strategies have allowed to unravel important aspects of the cellular origin of memory, and have started to shed new light on the neuronal networks involved in encoding, consolidation and retrieval of memory in the hippocampus. In particular, memory traces, or engrams, that are formed during encoding in the dentate gyrus and CA3 region are crucial for memory retrieval and amenable to modulation by neuroplastic mechanisms, including adult hippocampal neurogenesis. Here, we will discuss how memory traces are being encoded at the cellular level, how they may contribute to pattern separation and pattern completion in the hippocampus, and how they can be associated with different experiences to express memories of opposite valence. We propose a mechanism by which adult hippocampal neurogenesis may contribute to the formation of engrams, which may be relevant not only for the encoding of contextual information, but also for mood abnormalities, such as anxiety and depression.

Keywords: BDNF; amygdala; dentate gyrus; entorhinal cortex; fear conditioning; immediate early genes; optogenetics; stem cells; stress.

Figure 1.

Figure showing encoding, retrieval and new learning with and without neurogenesis. (A) left: immediate early gene activation (Arc, c-fos) in the dentate gyrus and CA3 region of the hippocampus during memory encoding (green cells). Right: During new learning, predominantly new cells are being activated in the dentate gyrus and CA3 (yellow cells). (B) During memory retrieval, a subset of cells that were activated during encoding are recruited (red cells), and new cells are being activated (yellow cells). (C) Without neurogenesis, memory retrieval is impaired and reactivation is decreased in CA3 but not in the dentate gyrus, as indicated by less co-labeling (red cells) than in (B).