Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Sep 2014
Phospholipase D2 specifically regulates TREK potassium channels via direct interaction and local production of phosphatidic acid.
Membrane lipids serve as second messengers and docking sites for proteins and play central roles in cell signaling. A major question about lipid signaling is whether diffusible lipids can selectively target specific proteins. One family of lipid-regulated membrane proteins is the TWIK-related K channel (TREK) subfamily of K2P channels: TREK1, TREK2, and TWIK-related arachdonic acid stimulated K(+) channel (TRAAK). ⋯ We found that PLD2, but not PLD1, directly binds to the C terminus of TREK1 and TREK2, but not to TRAAK. The results have led to a model for selective lipid regulation by localization of phospholipid enzymes to specific effector proteins. Finally, we show that regulation of TREK channels by PLD2 occurs natively in hippocampal neurons.
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Human strategic interaction requires reasoning about other people's behavior and mental states, combined with an understanding of their incentives. However, the ontogenic development of strategic reasoning is not well understood: At what age do we show a capacity for sophisticated play in social interactions? Several lines of inquiry suggest an important role for recursive thinking (RT) and theory of mind (ToM), but these capacities leave out the strategic element. We posit a strategic theory of mind (SToM) integrating ToM and RT with reasoning about incentives of all players. ⋯ These two results also correspond to two ways in which children's behavior resembles adult behavior in the same games. In both games, children's behavior becomes more strategically sophisticated with age on the first move. Beyond the age of 7 y, children begin to think about strategic interaction not myopically, but in a farsighted way, possibly with a view to cooperating and capitalizing on mutual gains in long-run relationships.
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Proc. Natl. Acad. Sci. U.S.A. · Sep 2014
Voltage-sensitive dye imaging of transcranial magnetic stimulation-induced intracortical dynamics.
Transcranial magnetic stimulation (TMS) is widely used in clinical interventions and basic neuroscience. Additionally, it has become a powerful tool to drive plastic changes in neuronal networks. However, highly resolved recordings of the immediate TMS effects have remained scarce, because existing recording techniques are limited in spatial or temporal resolution or are interfered with by the strong TMS-induced electric field. ⋯ Furthermore, loss of the "deceleration-acceleration" notch during the rising phase of the response, as a signature of fast intracortical inhibition detectable with VSD imaging, indicated weakened inhibition as an important driving force of increasing cortical excitability. In summary, our data show that high-frequency TMS changes the balance between excitation and inhibition in favor of an excitatory cortical state. VSD imaging may thus be a promising technique to trace TMS-induced changes in excitability and resulting plastic processes across cortical maps with high spatial and temporal resolutions.
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Proc. Natl. Acad. Sci. U.S.A. · Sep 2014
Optogenetic neuronal stimulation promotes functional recovery after stroke.
Clinical and research efforts have focused on promoting functional recovery after stroke. Brain stimulation strategies are particularly promising because they allow direct manipulation of the target area's excitability. However, elucidating the cell type and mechanisms mediating recovery has been difficult because existing stimulation techniques nonspecifically target all cell types near the stimulated site. ⋯ Moreover, iM1 neuronal stimulations promoted functional recovery, as stimulated stroke mice showed faster weight gain and performed significantly better in sensory-motor behavior tests. Interestingly, stimulations in normal nonstroke mice did not alter motor behavior or neurotrophin expression, suggesting that the prorecovery effect of selective neuronal stimulations is dependent on the poststroke environment. These results demonstrate that stimulation of neurons in the stroke hemisphere is sufficient to promote recovery.