Mini Mental State

Atlas of the Human Brain.

Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by a number of environmental and cell-intrinsic factors to adapt to environmental changes. Accumulating evidence suggests that adult-born neurons may play distinct physiological roles in hippocampus-dependent functions, such as memory encoding and mood regulation. In addition, several brain diseases, such as neurological diseases and mood disorders, have deleterious effects on adult hippocampal neurogenesis, and some symptoms of those diseases can be partially explained by the dysregulation of adult hippocampal neurogenesis. Here we review a possible link between the physiological functions of adult-born neurons and their roles in pathological conditions.

The role of adult hippocampal neurogenesis in brain health and disease

New neurons continue to be generated in the dentate gyrus throughout life, providing this region of the hippocampus with exceptional structural plasticity, but the function of this ongoing neurogenesis is unknown. Inhibition of adult neurogenesis produces some behavioral impairments that suggest a role for new neurons in learning and memory; however, other behavioral changes appear inconsistent with this function. A review of studies investigating the function of the hippocampus going back several decades reveals many ideas that seem to converge on a critical role for the hippocampus in stress response and emotion. These potential hippocampal functions provide new avenues for investigating the behavioral functions of adult neurogenesis. And, conversely, studies in animals lacking adult neurogenesis, which are likely to have more limited and more specific impairments than are seen with lesions, may provide valuable new insights into the function of the hippocampus. A complete understanding of the function ...

/pdf/adult-neurogenesis-beyond-learning-and-memory-3k9ulprub2.pdf

Adult Neurogenesis: Beyond Learning and Memory*

Alzheimer’s Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.

/pdf/digital-biomarkers-for-alzheimer-s-disease-the-mobile-1j27cqc6yc.pdf

Digital biomarkers for Alzheimer's disease: the mobile/ wearable devices opportunity.

Memories for similar experiences can be either differentiated or integrated in the adult brain to support later memory retrieval and memory-based decision making. Yet how children represent related memories remains unknown. Here, children (7-10 years) and adults formed memories for separate yet overlapping events. We then measured how successfully remembered events were represented and reinstated using functional magnetic resonance imaging (fMRI). Both children and adults formed differentiated representations in hippocampus—such that related events were stored as less similar than unrelated events. Conversely, only adults formed integrated representations in medial prefrontal cortex (mPFC). Furthermore, hippocampal differentiation among children and mPFC integration among adults tracked neocortical reinstatement of the specific features associated with the individual events. Together, these findings reveal that the same memory behaviors are supported by different underlying representations across development. Specifically, whereas differentiation underlies memory organization and retrieval in childhood, integration exhibits a protracted developmental trajectory.

https://www.biorxiv.org/content/biorxiv/early/2023/05/25/2023.05.25.541743.full.pdf

Differentiation of related events in hippocampus supports memory reinstatement in development

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. Here, we tested this idea using high-resolution, pattern-based fMRI analyses. We show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. Strikingly, the magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide novel insight into why remapping occurs.

/pdf/abrupt-remapping-in-human-ca3-dentate-gyrus-signals-3kaqtph9ez.pdf

Robert J. Molitor

Papers

Differentiation of related events in hippocampus supports memory reinstatement in development

Abrupt remapping in human CA3/dentate gyrus signals resolution of memory interference