The Hippocampal Engram as a Memory Index

Abstract

The hippocampus encodes memories for past events, but the nature of the hippocampal code subserving this function remains unclear. A prevailing idea, strongly supported by hippocampal physiology, is the Cognitive Map Theory. In this view, episodic memories are anchored to spatial domains, or allocentric frameworks, of experiences, with the hippocampus providing a stable representation of external space. On the other hand, recent studies using Immediate Early Genes (IEGs) as a proxy of neuronal activation support the Memory Index Theory. This idea posits that the hippocampal memory trace serves as an index for a cortical representation of memory (a map for internal representation) and hypothesizes the primary hippocampal function is to reinstate the pattern of cortical activity present during encoding. Our recent findings provide a unitary view on these two fundamentally different theories. In the hippocampal CA1 region the activity of c-Fos expressing pyramidal neurons reliably reflects the identity of the context the animal is experiencing in an index-like fashion, while spikes from other active pyramidal cells provide spatial information that is stable over a long period of time. These two distinct ensembles of hippocampal neurons suggest heterogeneous roles for subsets of hippocampus neurons in memory.

Keywords: Hippocampus; engram; memory; place cell; plasticity.

Figure 1.

Two theories addressing a primary role of the hippocampus for episodic memory. (A) A subset of pyramidal neurons in the hippocampus is recruited for a given context and represents a specific location within the environment. O’Keefe and Nadel proposed spatial maps in the hippocampus being substrates for episodic memories. (B) Memory Index Theory assumes memory trace being a strengthened link between hippocampal and cortical representations. Once this memory trace is established during encoding, a partial input is sufficient to reactivate the complete memory representation in the hippocampus. This reinstates the original pattern of activity in the cortex and produces a sense of memory recall.

Figure 2.

Two distinct memory traces in the hippocampal CA1. (A) Heat maps showing firing locations of representative c-Fos-positive/negative place cells when animal is exposed to a novel context A (left), a familiar context A (middle), and a novel context B (right). (B) Context Discrimination Index defined from firing rate correlations of c-Fos-positive (orange) or negative (gray) place cells when animal explores context A/A or A/B.