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From Engrams to Pathologies of the Brain

View Article: PubMed Central - PubMed

ABSTRACT

Memories are the experiential threads that tie our past to the present. The biological realization of a memory is termed an engram—the enduring biochemical and physiological processes that enable learning and retrieval. The past decade has witnessed an explosion of engram research that suggests we are closing in on boundary conditions for what qualifies as the physical manifestation of memory. In this review, we provide a brief history of engram research, followed by an overview of the many rodent models available to probe memory with intersectional strategies that have yielded unprecedented spatial and temporal resolution over defined sets of cells. We then discuss the limitations and controversies surrounding engram research and subsequently attempt to reconcile many of these views both with data and by proposing a conceptual shift in the strategies utilized to study memory. We finally bridge this literature with human memory research and disorders of the brain and end by providing an experimental blueprint for future engram studies in mammals. Collectively, we believe that we are in an era of neuroscience where engram research has transitioned from ephemeral and philosophical concepts to provisional, tractable, experimental frameworks for studying the cellular, circuit and behavioral manifestations of memory.

No MeSH data available.


Related in: MedlinePlus

Better together: the practical utility lies somewhere in between. The Diagnostic and Statistical Manual of Mental Disorders (DSM) has received much criticism because its system of descriptive diagnostic nosology does not lend itself to being concretely linked to the circuitry of the brain, which renders the DSM difficult to use as a construct that motivates hypothesis-driven neuroscience research. The Research Domain Criteria (RDoC) framework has suffered from the opposite problem. Namely, it specifies empirically derived domains that are clearly tied to brain circuits, but do not clearly link to disease symptomology as defined by the DSM. Particularly as intermediate phenotypes are better defined in human patient populations and reconciled with circuit-level observations from animal studies, the functionalization of the RDoCs framework can occur and be more accurately mapped onto the symptom-driven DSM nosology to achieve a middle ground that is practically useful by both physicians and researchers.
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Figure 3: Better together: the practical utility lies somewhere in between. The Diagnostic and Statistical Manual of Mental Disorders (DSM) has received much criticism because its system of descriptive diagnostic nosology does not lend itself to being concretely linked to the circuitry of the brain, which renders the DSM difficult to use as a construct that motivates hypothesis-driven neuroscience research. The Research Domain Criteria (RDoC) framework has suffered from the opposite problem. Namely, it specifies empirically derived domains that are clearly tied to brain circuits, but do not clearly link to disease symptomology as defined by the DSM. Particularly as intermediate phenotypes are better defined in human patient populations and reconciled with circuit-level observations from animal studies, the functionalization of the RDoCs framework can occur and be more accurately mapped onto the symptom-driven DSM nosology to achieve a middle ground that is practically useful by both physicians and researchers.

Mentions: A cross-species framework, similar to a cross-species study of memory, could enable the RDoC and DSM camps to meet on a middle ground of functional utility (Figure 3). This sort of cross-species approach to engram research fits within the existing RDoC structure can be extended in multiple ways. It adds a causal understanding of memory processes that can be linked to the domains of cognitive systems. By being anchored around human functional neuroscience, genetics, and the endophenotyping of human clinical populations, the conceptual advance of our proposed framework is a call to arms to begin earnestly linking disease symptomology to psychiatric and neurologic endophenotypes of disease and the underlying affected neural circuitry.


From Engrams to Pathologies of the Brain
Better together: the practical utility lies somewhere in between. The Diagnostic and Statistical Manual of Mental Disorders (DSM) has received much criticism because its system of descriptive diagnostic nosology does not lend itself to being concretely linked to the circuitry of the brain, which renders the DSM difficult to use as a construct that motivates hypothesis-driven neuroscience research. The Research Domain Criteria (RDoC) framework has suffered from the opposite problem. Namely, it specifies empirically derived domains that are clearly tied to brain circuits, but do not clearly link to disease symptomology as defined by the DSM. Particularly as intermediate phenotypes are better defined in human patient populations and reconciled with circuit-level observations from animal studies, the functionalization of the RDoCs framework can occur and be more accurately mapped onto the symptom-driven DSM nosology to achieve a middle ground that is practically useful by both physicians and researchers.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5383718&req=5

Figure 3: Better together: the practical utility lies somewhere in between. The Diagnostic and Statistical Manual of Mental Disorders (DSM) has received much criticism because its system of descriptive diagnostic nosology does not lend itself to being concretely linked to the circuitry of the brain, which renders the DSM difficult to use as a construct that motivates hypothesis-driven neuroscience research. The Research Domain Criteria (RDoC) framework has suffered from the opposite problem. Namely, it specifies empirically derived domains that are clearly tied to brain circuits, but do not clearly link to disease symptomology as defined by the DSM. Particularly as intermediate phenotypes are better defined in human patient populations and reconciled with circuit-level observations from animal studies, the functionalization of the RDoCs framework can occur and be more accurately mapped onto the symptom-driven DSM nosology to achieve a middle ground that is practically useful by both physicians and researchers.
Mentions: A cross-species framework, similar to a cross-species study of memory, could enable the RDoC and DSM camps to meet on a middle ground of functional utility (Figure 3). This sort of cross-species approach to engram research fits within the existing RDoC structure can be extended in multiple ways. It adds a causal understanding of memory processes that can be linked to the domains of cognitive systems. By being anchored around human functional neuroscience, genetics, and the endophenotyping of human clinical populations, the conceptual advance of our proposed framework is a call to arms to begin earnestly linking disease symptomology to psychiatric and neurologic endophenotypes of disease and the underlying affected neural circuitry.

View Article: PubMed Central - PubMed

ABSTRACT

Memories are the experiential threads that tie our past to the present. The biological realization of a memory is termed an engram—the enduring biochemical and physiological processes that enable learning and retrieval. The past decade has witnessed an explosion of engram research that suggests we are closing in on boundary conditions for what qualifies as the physical manifestation of memory. In this review, we provide a brief history of engram research, followed by an overview of the many rodent models available to probe memory with intersectional strategies that have yielded unprecedented spatial and temporal resolution over defined sets of cells. We then discuss the limitations and controversies surrounding engram research and subsequently attempt to reconcile many of these views both with data and by proposing a conceptual shift in the strategies utilized to study memory. We finally bridge this literature with human memory research and disorders of the brain and end by providing an experimental blueprint for future engram studies in mammals. Collectively, we believe that we are in an era of neuroscience where engram research has transitioned from ephemeral and philosophical concepts to provisional, tractable, experimental frameworks for studying the cellular, circuit and behavioral manifestations of memory.

No MeSH data available.


Related in: MedlinePlus