Engram cell connectivity: an evolving substrate for information storage

Ryan, Tomás J.; Pezzoli, Maurizio; Sen, Siddhartha

doi:10.1016/j.conb.2021.01.006

Cited by 20 publications

(17 citation statements)

References 135 publications

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“…Either by extrasynaptic or synaptic communication, only specific synapses are formed between a given subset of engram cells after experiences. The specificity of the connections formed during learning has precisely been hypothesized to be the mechanism at the center of memory storage, as it will be discussed later (153,154).…”

Section: Synaptic Allocationmentioning

confidence: 99%

“…At this point, it is important to make a distinction between plasticity mechanisms that modify synaptic weight (the strength of a particular synapse) and plasticity mechanisms that modify synaptic wiring (the flowchart diagram of connections in between neurons or structural plasticity) (23). One hypothesis is that memory is stored in the stable connectivity pattern between engram cells (153,154), which remains unaltered in memories that can be reactivated by artificial (induced by light) but not natural recall (induced by contextual cues) (46). Molecular mechanisms involved in specifically creating and maintaining this connectivity are still to be fully understood.…”

Section: Storing As Connectionsmentioning

confidence: 99%

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Understanding the physical basis of memory: Molecular mechanisms of the engram

Ryan

2022

Journal of Biological Chemistry

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Section: Synaptic Allocationmentioning

confidence: 99%

Section: Storing As Connectionsmentioning

confidence: 99%

Understanding the physical basis of memory: Molecular mechanisms of the engram

Ryan

2022

Journal of Biological Chemistry

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“…There are few plausible candidate proteins currently available that can play such a role, and there is no clear mechanism for quickly storing information in such long lived objects such as polynucleotide chains (but see Akhlaghpour, 2022). A viable system exists that plasticity of synaptic wiring between cells may alter the connectome to store a stable memory as stable microanatomical engrams (Ryan, 2021). Though plausible this hypothesis provides only a substrate for engram formation but no clear insight into information coding.…”

Section: Discussionmentioning

confidence: 99%

A Topological Study of a Surface Signaling Network with Relevance to Brain Function

Sen

2022

Preprint

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A special charged surface network with surface spin half particles on it, that can be arranged in topologically inequivalent ways, is introduced. It is shown that action potential-like signals can be generated in the network in response to local surface deformations of a particular kind. Signals generated in this way carry details of the deformation that create them as a form of plasticity that influences the pathways they traverse leaving a topologically stable helical array of spins: a potential memory substrate. The structure is a non transient alignment of surface spins in response to the transient magnetic field generated by the moving charges present in the action potential-like voltage signals generated since particles with spin have magnetic properties. The structure has a natural excitation frequency that may play a role in memory retrieval. Signal generation and memory storage are proposed to depend on the existence of a surface spin structure. We show that such a surface network can capture the intricate topological features of any connectome in the brain. In addition biophysical properties of such a network are examined in order to constrain predictions of how it may function.

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“…In terms of therapeutic utility, it is noteworthy that psilocybin leads to more vivid and visual recollections, associated with enhanced activation of visual and sensory cortical regions after viewing positive autobiographical memory cues (145). In terms of advancing the mechanistic understanding, undoubtedly future preclinical studies will delve into the impact of psychedelics on memory engram storage and retrieval (146,147).…”

Section: Fear and Threat Systemsmentioning

confidence: 99%

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

et al. 2021

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Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

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Engram cell connectivity: an evolving substrate for information storage

Cited by 20 publications

References 135 publications

Understanding the physical basis of memory: Molecular mechanisms of the engram

Understanding the physical basis of memory: Molecular mechanisms of the engram

A Topological Study of a Surface Signaling Network with Relevance to Brain Function

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

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