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5 Publications

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    The prefrontal cortex (PFC)'s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - that is differences in the rate, sequence, phase, or covariance of firing. This suggests that such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.

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    The prefrontal cortex (PFC)'s functions are thought to include working memory, as its activity can reflect information that must be temporarily maintained to realize the current goal. We designed a flexible spatial working memory task that required rats to navigate - after distractions and a delay - to multiple possible goal locations from different starting points and via multiple routes. This made the current goal location the key variable to remember, instead of a particular direction or route to the goal. However, across a broad population of PFC neurons, we found no evidence of current-goal-specific memory in any previously reported form - that is differences in the rate, sequence, phase, or covariance of firing. This suggests that such patterns do not hold working memory in the PFC when information must be employed flexibly. Instead, the PFC grouped locations representing behaviorally equivalent task features together, consistent with a role in encoding long-term knowledge of task structure.

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    12/07/20 | The claustrum.
    Smith JB, Lee AK, Jackson J
    Current Biology. 2020 Dec 07;30(23):R1401-R1406. doi: 10.1016/j.cub.2020.09.069

    The claustrum is a brain region that has been investigated for over 200 years, yet its precise function remains unknown. In the final posthumously released article of Francis Crick, written with Christof Koch, the claustrum was suggested to be critically linked to consciousness. Though the claustrum remained relatively obscure throughout the last half century, it has enjoyed a renewed interest in the last 15 years since Crick and Koch's article. During this time, the claustrum, like many other brain regions, has been studied with the myriad of modern systems neuroscience tools that have been made available by the intersection of genetic and viral technologies. This has uncovered new information about its anatomical connectivity and physiological properties and begun to reveal aspects of its function. From these studies, one clear consensus has emerged which supports Crick and Koch's primary interest in the claustrum: the claustrum has widespread extensive connectivity with the entire cerebral cortex, suggesting a prominent role in 'higher order processes'.

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    10/29/20 | The Statistical Structure of the Hippocampal Code for Space as a Function of Time, Context, and Value.
    Lee JS, Briguglio JJ, Cohen JD, Romani S, Lee AK
    Cell. 2020 Oct 29;183(3):620-35. doi: 10.1016/j.cell.2020.09.024

    Hippocampal activity represents many behaviorally important variables, including context, an animal's location within a given environmental context, time, and reward. Using longitudinal calcium imaging in mice, multiple large virtual environments, and differing reward contingencies, we derived a unified probabilistic model of CA1 representations centered on a single feature-the field propensity. Each cell's propensity governs how many place fields it has per unit space, predicts its reward-related activity, and is preserved across distinct environments and over months. Propensity is broadly distributed-with many low, and some very high, propensity cells-and thus strongly shapes hippocampal representations. This results in a range of spatial codes, from sparse to dense. Propensity varied ∼10-fold between adjacent cells in salt-and-pepper fashion, indicating substantial functional differences within a presumed cell type. Intracellular recordings linked propensity to cell excitability. The stability of each cell's propensity across conditions suggests this fundamental property has anatomical, transcriptional, and/or developmental origins.

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    07/01/20 | The anatomy and physiology of claustrum-cortex interactions.
    Jackson J, Smith JB, Lee AK
    Annual Review of Neuroscience. 2020 Jul 1;43:231-47. doi: 10.1146/annurev-neuro-092519-101637

    The claustrum is one of the most widely connected regions of the forebrain, yet its function has remained obscure, largely due to the experimentally challenging nature of targeting this small, thin, and elongated brain area. However, recent advances in molecular techniques have enabled the anatomy and physiology of the claustrum to be studied with the spatiotemporal and cell type-specific precision required to eventually converge on what this area does. Here we review early anatomical and electrophysiological results from cats and primates, as well as recent work in the rodent, identifying the connectivity, cell types, and physiological circuit mechanisms underlying the communication between the claustrum and the cortex. The emerging picture is one in which the rodent claustrum is closely tied to frontal/limbic regions and plays a role in processes, such as attention, that are associated with these areas. Expected final online publication date for the , Volume 43 is July 8, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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