Still searching for the engram

Abstract

For nearly a century neurobiologists have searched for the engram - the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories.

Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

“…The distributed nature of engram cell ensembles for a specific memory has led to the suggestion that the memory engram within an individual brain region may contribute a subset of the overall memory information (Eichenbaum, 2016;Roy et al, 2017b). For example, hippocampal engrams are thought to primarily contribute contextual information by acting as an index for cortical memories of various sensory modalities (Teyler and DiScenna, 1986;Teyler and Rudy, 2007), whereas amygdala engrams hold valence information for a given experience (Janak and Tye, 2015;Morrison and Salzman, 2010;Redondo et al, 2014;Tovote et al, 2015).…”

From Engrams to Pathologies of the Brain

“…As such, artificially recapitulating natural firing patterns may produce three outcomes: it is not effective, it is just as effective, or it is more effective at activating various components of a memory (Häusser, 2014). The latter conjecture is supported by recent data in CA1, in which neuronal ensembles display precisely timed sequences of activity in response to spatial-temporal relational processing, which together are believed to comprise the global structure of an experience (Wood et al, 1999; MacDonald et al, 2011; Buzsáki and Moser, 2013; Eichenbaum, 2016). Despite the success of a 20 Hz stimulation protocol in the DG, Ramirez et al (2013) failed to observe light-induced memory retrieval in response to the same 20 Hz protocol in CA1.…”

“…Rather than provide an exhaustive historical overview of engram research, here we discuss the strengths, weaknesses, caveats and controversies that have ensued in the last 10 years, beginning in the late 2000s when pioneering studies on memory introduced the genetic strategies often utilized today to study defined sets of cells and circuits processing discrete mnemonic information. Readers are referred elsewhere for thorough overviews on the historical trajectory and experimental breakthroughs that greatly influenced the modern search for the engram (Mayford, 2014; Gore et al, 2015b; Josselyn et al, 2015; Tonegawa et al, 2015; Eichenbaum, 2016). …”

To master memory, researchers pursue its roots

“…(Unfortunately for Lashley, many of these regions lie outside of the cerebral cortex.) The hippocampus plays a key role in spatial memory, for example, and the amygdala mediates fearful memories, whereas the cerebellum is essential for certain types of Pavlovian conditioning (2). Now, researchers have zeroed in on specific networks of neurons that appear to hold memories, or at least key components of memories.…”