If engrams are the answer, what is the question?

Abstract

Engram labelling and manipulation methodologies are now a staple of contemporary neuroscientific practice, giving the impression that the physical basis of engrams has been discovered. Despite enormous progress, engrams have not been clearly identified, and it is unclear what they should looklike. There is an epistemic bias in engram neuroscience towards characterising biological changes,while neglecting the development of theory. However, the tools of engram biology are excitingprecisely because they are not just an incremental step forward in understanding the mechanisms ofplasticity and learning, but because they can be leveraged to inform theory on one of the fundamental mysteries in neuroscience—how and in what format the brain stores information. We do not propose such a theory here, as we first require an appreciation for what is lacking. We outline a selection ofissues in four sections from theoretical biology and philosophy that engram biology and systems neuroscience generally should engage with in order to construct useful future theoretical frameworks.Specifically, what is it that engrams are supposed to explain? How do the different building blocks of the brain-wide engram come together? What exactly are these component parts? And what information do they carry, if they carry anything at all? Asking these questions is not purely the privilege of philosophy, but a key to informing scientific hypotheses that make the most of the experimental tools at our disposal. The risk for not engaging with these issues is high. Without a theory of what engrams are, what they do, and the wider computational processes they fit into, we may never know when they have been found.

Rethinking Memory Impairments: Retrieval Failure

“…memory and their precise characteristics remain still uncertain (for elaborate and recent reviews, seeGuskjolen & Cembrowski, 2023;O'Sullivan & Ryan, 2023;Queenan, Ryan, Gazzaniga, & Gallistel, 2017;Ryan, Ortega-de San Luis, Pezzoli, & Sen, 2021). Thus, in light of the extensive behavioural and refined neurobiological empirical studies reorienting our understanding of the neurobiological mechanisms of memory storage and forgetting, and how forgetting can be induced and rescued, it is simpler to conclude that amnesic interventions typically used by advocates of the consolidation/reconsolidation frameworks might simply alter the neurobiological basis of the memory's subsequent retrievability or expression, but not memory (re)storage mechanisms.…”