Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity

Tetraspanins (Tspan) are transmembrane proteins with important scaffold and signalling functions. Deletions of Tetraspanin 6 (Tspan6) gene, a member of the tetraspanin family, have been reported in patients with Epilepsy Female-restricted with Mental Retardation (EFMR). Interestingly, mutations in Tspan7, highly homologous to Tspan6, are associated with X-linked intellectual disability, suggesting that these two proteins are important for cognition. Considering recent evidences showing that Tspan7 plays a key role in synapse development and AMPAR trafficking, we initiated the study of Tspan6 in synaptic function using a Tspan6 knock out mouse model. Here we report that hippocampal field recordings from Tspan6 knock out mice show an enhanced basal synaptic transmission and impaired long term potentiation (LTP). A normal paired-pulse facilitation response suggests that Tspan6 affects the properties of the postsynaptic rather than the presynaptic terminal. However, no changes in spine morphology or postsynaptic markers could be detected in Tspan6 KO mice compared with wild types. In addition, Tspan6 KO mice show normal locomotor behaviour and no defects in hippocampus-dependent memory tests

Quivers, Tilings, Branes and Rhombi

We describe a simple algorithm that computes the recently discovered brane tilings for a given generic toric singular Calabi-Yau threefold. This therefore gives AdS/CFT dual quiver gauge theories for D3-branes probing the given non-compact manifold. The algorithm solves a longstanding problem by computing superpotentials for these theories directly from the toric diagram of the singularity. We study the parameter space of a-maximization; this study is made possible by identifying the R-charges of bifundamental fields as angles in the brane tiling. We also study Seiberg duality from a new perspective.Comment: 36 pages, 40 figures, JHEP

Increased Insoluble Amyloid-β Induces Negligible Cognitive Deficits in Old AppNL/NL Knock-In Mice

Commonly used Alzheimer's disease mouse models are based on the ectopic overexpression of the human amyloid precursor protein (APP) gene, together with a mutant presenilin gene. Surprisingly, humanized APP knock-in mouse models carrying a single APP Swedish mutation (AppNL), failed to develop amyloid plaque aggregation or cognitive deficits. Here we characterized the effect of this mutation in more advanced ages. We show that 24-month-old AppNL/NL mice, despite presenting an age dependent increase in insoluble amyloid-β oligomers in the prefrontal cortex, they do not develop amyloid plaque deposition, reactive gliosis, or cognitive deficits

Non-relativistic metrics from back-reacting fermions

It has recently been pointed out that under certain circumstances the back-reaction of charged, massive Dirac fermions causes important modifications to AdS_2 spacetimes arising as the near horizon geometry of extremal black holes. In a WKB approximation, the modified geometry becomes a non-relativistic Lifshitz spacetime. In three dimensions, it is known that integrating out charged, massive fermions gives rise to gravitational and Maxwell Chern-Simons terms. We show that Schrodinger (warped AdS_3) spacetimes exist as solutions to a gravitational and Maxwell Chern-Simons theory with a cosmological constant. Motivated by this, we look for warped AdS_3 or Schrodinger metrics as exact solutions to a fully back-reacted theory containing Dirac fermions in three and four dimensions. We work out the dynamical exponent in terms of the fermion mass and generalize this result to arbitrary dimensions.Comment: 26 pages, v2: typos corrected, references added, minor change

Brane Tilings and Exceptional Collections

Both brane tilings and exceptional collections are useful tools for describing the low energy gauge theory on a stack of D3-branes probing a Calabi-Yau singularity. We provide a dictionary that translates between these two heretofore unconnected languages. Given a brane tiling, we compute an exceptional collection of line bundles associated to the base of the non-compact Calabi-Yau threefold. Given an exceptional collection, we derive the periodic quiver of the gauge theory which is the graph theoretic dual of the brane tiling. Our results give new insight to the construction of quiver theories and their relation to geometry.Comment: 46 pages, 37 figures, JHEP3; v2: reference added, figure 13 correcte

Strange metals and the AdS/CFT correspondence

I begin with a review of quantum impurity models in condensed matter physics, in which a localized spin degree of freedom is coupled to an interacting conformal field theory in d = 2 spatial dimensions. Their properties are similar to those of supersymmetric generalizations which can be solved by the AdS/CFT correspondence; the low energy limit of the latter models is described by a AdS2 geometry. Then I turn to Kondo lattice models, which can be described by a mean- field theory obtained by a mapping to a quantum impurity coupled to a self-consistent environment. Such a theory yields a 'fractionalized Fermi liquid' phase of conduction electrons coupled to a critical spin liquid state, and is an attractive mean-field theory of strange metals. The recent holographic description of strange metals with a AdS2 x R2 geometry is argued to be related to such mean-field solutions of Kondo lattice models.Comment: 19 pages, 4 figures; Plenary talk at Statphys24, Cairns, Australia, July 2010; (v2) added refs; (v3) more ref

Correction: Tetraspanin 6: A novel regulator of hippocampal synaptic transmission and long term plasticity

[This corrects the article DOI: 10.1371/journal.pone.0171968.]

Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease

Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition. We find the same early cingulate FC disruption and neuronal hyperactivity in AppNL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astrocytic calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral disruptions. In conclusion, we show that astrocytes mediate initial features of AD and drive clinically relevant phenotypes