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Neuron
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Oct 21, 2015

Volume 88Issue 2p237-434
Open Archive
On the cover: The blood-brain barrier (BBB) limits uptake of both harmful and therapeutic molecules into the brain. It has been proposed that widespread BBB disruption in neurodegenerative diseases, in particular Alzheimer's disease (AD), may accelerate or even cause disease. This widespread disease-related leakiness may also allow for uptake of therapeutic molecules, including antibodies. In this issue, Bien-Ly et al. (pages 289–297) provide evidence from multiple preclinical AD models that passive BBB permeability to therapeutic antibodies is not increased as a result of disease. The cover image illustrates the brick wall that the BBB presents for the accessibility of therapeutic molecules, even in the context of Alzheimer's disease, highlighting the resiliency of the BBB and the necessity of approaches designed to enhance brain uptake of therapeutic molecules....
On the cover: The blood-brain barrier (BBB) limits uptake of both harmful and therapeutic molecules into the brain. It has been proposed that widespread BBB disruption in neurodegenerative diseases, in particular Alzheimer's disease (AD), may accelerate or even cause disease. This widespread disease-related leakiness may also allow for uptake of therapeutic molecules, including antibodies. In this issue, Bien-Ly et al. (pages 289–297) provide evidence from multiple preclinical AD models that passive BBB permeability to therapeutic antibodies is not increased as a result of disease. The cover image illustrates the brick wall that the BBB presents for the accessibility of therapeutic molecules, even in the context of Alzheimer's disease, highlighting the resiliency of the BBB and the necessity of approaches designed to enhance brain uptake of therapeutic molecules.
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  • Re-evaluation of the Blood-Brain Barrier in the Presence of Alzheimer’s Disease Pathology

    • Jason D. Ulrich,
    • Tien-Phat Huynh,
    • David M. Holtzman
    Blood-brain barrier disruption is believed to occur in Alzheimer’s disease, which could influence the bioavailability of drugs within the brain. However, in this issue of Neuron, Bien-Ly et al. (2015) report no evidence of widespread blood-brain barrier dysfunction.

  • A Direct Path to Action Initiation

    • Christopher H. Donahue,
    • Anatol C. Kreitzer
    In this issue of Neuron, Sippy et al. (2015) provide the clearest evidence to date that information is differentially encoded in the direct and indirect pathways of the striatum. The results support the classical notion that the direct pathway plays a critical role in initiating actions.

  • Default Distance Coding Properties in the Hippocampus

    • Sam McKenzie,
    • György Buzsáki
    Whereas hippocampal activity is thought to be driven by precise conjunctions of sensory input, a recent study by Villette and Malvache et al. reveals that neurons imaged in a static sensory environment organize into sequences endowed with intrinsic spatiotemporal properties.

  • Processing Timescales as an Organizing Principle for Primate Cortex

    • Janice Chen,
    • Uri Hasson,
    • Christopher J. Honey
    An emerging view posits a timescale-based cortical topography, with integration windows increasing from sensory to association areas. In this issue, Chaudhuri et al. (2015) present a cortical model wherein a hierarchy of timescales arises from local and inter-regional circuit dynamics.

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  • Lack of Widespread BBB Disruption in Alzheimer’s Disease Models: Focus on Therapeutic Antibodies

    • Nga Bien-Ly,
    • C. Andrew Boswell,
    • Surinder Jeet,
    • Thomas G. Beach,
    • Kwame Hoyte,
    • Wilman Luk,
    • Vera Shihadeh,
    • Sheila Ulufatu,
    • Oded Foreman,
    • Yanmei Lu,
    • Jason DeVoss,
    • Marcel van der Brug,
    • Ryan J. Watts
    It is generally believed that neurodegeneration is accompanied by BBB dysfunction, potentially increasing drug bioavailability in the CNS. Bien-Ly et al. report that AD mouse models lack widespread BBB disruption and display restricted passive permeability to therapeutic antibodies.

  • Cell-Type-Specific Sensorimotor Processing in Striatal Projection Neurons during Goal-Directed Behavior

    • Tanya Sippy,
    • Damien Lapray,
    • Sylvain Crochet,
    • Carl C.H. Petersen
    Sippy et al. measure cell-type-specific membrane potential dynamics in the striatum of head-restrained mice performing a simple goal-directed sensorimotor transformation. Their results are consistent with direct pathway striatonigral neurons delivering a fast “go” signal for action initiation.

  • Habenular CB1 Receptors Control the Expression of Aversive Memories

    • Edgar Soria-Gómez,
    • Arnau Busquets-Garcia,
    • Fei Hu,
    • Amine Mehidi,
    • Astrid Cannich,
    • Liza Roux,
    • Ines Louit,
    • Lucille Alonso,
    • Theresa Wiesner,
    • Francois Georges,
    • Danièle Verrier,
    • Peggy Vincent,
    • Guillaume Ferreira,
    • Minmin Luo,
    • Giovanni Marsicano
    Soria-Gómez et al. show that CB1 receptors expressed at presynaptic terminals of medial habenula neurons projecting to the interpeduncular nucleus specifically control the expression of aversive memories. This function requires negative control of cholinergic, but not glutamatergic, neurotransmission.

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