A chemogenetic approach for dopamine imaging with tunable sensitivity.

Genetically-encoded dopamine (DA) sensors enable high-resolution imaging of DA release, but their ability to detect a wide range of extracellular DA levels, especially tonic versus phasic DA release, is limited by their intrinsic affinity. Here we show that a human-selective dopamine receptor positive allosteric modulator (PAM) can be used to boost sensor affinity on-demand. The PAM enhances DA detection sensitivity across experimental preparations (in vitro, ex vivo and in vivo) via one-photon or two-photon imaging.

Sampling bias corrections for accurate neural measures of redundant, unique, and synergistic information.

Shannon Information theory has long been a tool of choice to measure empirically how populations of neurons in the brain encode information about cognitive variables. Recently, Partial Information Decomposition (PID) has emerged as principled way to break down this information into components identifying not only the unique information carried by each neuron, but also whether relationships between neurons generate synergistic or redundant information. While it has been long recognized that Shannon information measures on neural activity suffer from a (mostly upward) limited sampling estimation bias, this issue has largely been ignored in the burgeoning field of PID analysis of neural activity.

Sensitive multicolor indicators for monitoring norepinephrine in vivo.

Genetically encoded indicators engineered from G-protein-coupled receptors are important tools that enable high-resolution in vivo neuromodulator imaging. Here, we introduce a family of sensitive multicolor norepinephrine (NE) indicators, which includes nLightG (green) and nLightR (red). These tools report endogenous NE release in vitro, ex vivo and in vivo with improved sensitivity, ligand selectivity and kinetics, as well as a distinct pharmacological profile compared with previous state-of-the-art GRAB indicators.

ASTRA: a deep learning algorithm for fast semantic segmentation of large-scale astrocytic networks.

Changes in the intracellular calcium concentration are a fundamental fingerprint of astrocytes, the main type of glial cell. Astrocyte calcium signals can be measured with two-photon microscopy, occur in anatomically restricted subcellular regions, and are coordinated across astrocytic networks. However, current analytical tools to identify the astrocytic subcellular regions where calcium signals occur are time-consuming and extensively rely on user-defined parameters.

Characterization of the interactome profiling of DnaK in cancer cells reveals interference with key cellular pathways.

Chaperone proteins are redundant in nature and, to achieve their function, they bind a large repertoire of client proteins. DnaK is a bacterial chaperone protein that recognizes misfolded and aggregated proteins and drives their folding and intracellular trafficking. Some Mycoplasmas are associated with cancers, and we demonstrated that infection with a strain of isolated in our lab promoted lymphoma in a mouse model.