Ultrastructural, Molecular and Functional Mapping of GABAergic Synapses on Dendritic Spines and Shafts of Neocortical Pyramidal Neurons.

The location of GABAergic synapses on dendrites is likely key for neuronal integration. In particular, inhibitory inputs on dendritic spines could serve to selectively veto or modulate individual excitatory inputs, greatly expanding the computational power of individual neurons. To investigate this, we have undertaken a combined functional, molecular, and ultrastructural mapping of the location of GABAergic inputs onto dendrites of pyramidal neurons from upper layers of juvenile mouse somatosensory cortex.

Engineering a genetically-encoded SHG chromophore by electrostatic targeting to the membrane.

Although second harmonic generation (SHG) microscopy provides unique imaging advantages for voltage imaging and other biological applications, genetically-encoded SHG chromophores remain relatively unexplored. SHG only arises from non-centrosymmetric media, so an anisotropic arrangement of chromophores is essential to provide strong SHG signals. Here, inspired by the mechanism by which K-Ras4B associates with plasma membranes, we sought to achieve asymmetric arrangements of chromophores at the membrane-cytoplasm interface using the fluorescent protein mVenus.

Developing ANDI: a novel approach to health product R&D in Africa.

Solomon Nwaka and colleagues discuss ANDI, the African Network for Drugs and Diagnostics Innovation, which is intended to help stimulate health research and development on the African continent.

Photorelease of GABA with Visible Light Using an Inorganic Caging Group.

We describe the selective photorelease of gamma-amino butyric acid (GABA) with a novel caged-GABA compound that uses a ruthenium complex as photosensor. This compound ("RuBi-GABA") can be excited with visible wavelengths, providing greater tissue penetration, less photo-toxicity, and faster photorelease kinetics than currently used UV light-sensitive caged compounds. Using pyramidal neurons from neocortical brain slices, we show that RuBi-GABA uncaging induces GABA-A receptor-mediated responses, has no detectable side effects on endogenous GABAergic and glutamatergic receptors and generates responses with kinetics and spatial resolution comparable to the best caged GABA compounds presently available.

Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission.

Arc/Arg3.1 is an immediate-early gene whose expression levels are increased by strong synaptic activation, including synapse-strengthening activity patterns. Arc/Arg3.