Identification of the cellular players and molecular messengers that communicate neuronal activity to the vasculature driving cerebral hemodynamics is important for (1) the basic understanding of cerebrovascular regulation and (2) interpretation of functional Magnetic Resonance Imaging (fMRI) signals. Using a combination of optogenetic stimulation and 2-photon imaging in mice, we demonstrate that selective activation of cortical excitation and inhibition elicits distinct vascular responses and identify the vasoconstrictive mechanism as Neuropeptide Y (NPY) acting on Y1 receptors. The latter implies that task-related negative Blood Oxygenation Level Dependent (BOLD) fMRI signals in the cerebral cortex under normal physiological conditions may be mainly driven by the NPY-positive inhibitory neurons. Further, the NPY-Y1 pathway may offer a potential therapeutic target in cerebrovascular disease.DOI: http://dx.doi.org/10.7554/eLife.14315.001

Controllable biaxial and uniaxial nanowrinkles (see figure) are fabricated by a simple two‐step approach — metal deposition and subsequent heating — based on shape memory polymer (prestressed polystyrene) sheets. The wavelengths of the wrinkles can be tuned by controlling the thickness of deposited metal. The ready integration of the nanowrinkles into microchannels and their effectiveness in surface enhanced sensing is demonstrated.

Background.-Functional Magnetic Resonance Imaging (fMRI) in awake behaving mice is well positioned to bridge the detailed cellular-level view of brain activity, which has become available due to recent advances in microscopic optical imaging and genetics, to the macroscopic scale of human noninvasive observables. However, while microscopic (e.g., 2-photon imaging) studies in behaving mice have become a reality in many laboratories, awake mouse fMRI remains a

Non-degenerate two-photon excitation (ND-TPE) has been explored in two-photon excitation microscopy. However, a systematic study of the efficiency of ND-TPE to guide the selection of fluorophore excitation wavelengths is missing. We measured the relative non-degenerate two-photon absorption cross-section (ND-TPACS) of several commonly used fluorophores (two fluorescent proteins and three small-molecule dyes) and generated 2-dimensional ND-TPACS spectra. We observed that the shape of a ND-TPACS spectrum follows that of the corresponding degenerate two-photon absorption cross-section (D-TPACS) spectrum, but is higher in magnitude. We found that the observed enhancements are higher than theoretical predictions.

Non-degenerate 2-photon excitation (ND-2PE) of a fluorophore with two laser beams of different photon energies offers an independent degree of freedom in tuning of the photon flux for each beam. This feature takes advantage of the infrared wavelengths used in degenerate 3-photon excitation (D-3PE) microscopy to achieve increased penetration depths, while preserving a relatively high 2-photon excitation cross section in comparison to that of D-3PE. Here, using spatially and temporally aligned Ti:Sapphire laser and optical parametric oscillator beams operating at near infrared (NIR) and short-wavelength infrared (SWIR) optical frequencies, we employ ND-2PE and provide a practical demonstration that a constant fluorophore emission intensity is achievable deeper into a scattering medium using ND-2PE as compared to the commonly used degenerate 2-photon excitation (D-2PE). References and links1. K. Svoboda and R. Yasuda, "Principles of two-photon excitation microscopy and its applications to neuroscience," Neuron 50(6), 823-839 (2006). 2. J. N. Kerr and W. Denk, "Imaging in vivo: watching the brain in action," Nat. Rev. Neurosci. 9(3), 195-205 (2008). 3. W. Denk and K. Svoboda, "Photon upmanship: why multiphoton imaging is more than a gimmick," Neuron 18(3), 351-357 (1997). 4. F. Helmchen and W. Denk, "Deep tissue two-photon microscopy," Nat. Methods 2(12), 932-940 (2005 11. D. Kobat, N. G. Horton, and C. Xu, "In vivo two-photon microscopy to 1.6-mm depth in mouse cortex," J. Biomed. Opt. 16(10), 106014 (2011). 12. R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, "Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser," Sci. Rep. 3, 1014 (2013). 13. P. Theer and W. Denk, "On the fundamental imaging-depth limit in two-photon microscopy," J. Opt. Soc. Am.A adaptive optical recovery of optimal resolution over large volumes," Nat. Methods 11(6), 625-628 (2014).

We demonstrate the formation and spatial modulation of strongly coupled gallium selenide quantum dot ͑QD͒ nanoassemblies suspended in a nematic liquid-crystal ͑NLC͒ matrix at room temperature. Using static and dynamic optical techniques we show that the coupled QDs aggregate with a well-defined directionality commensurate with the NLC director axis. This results in highly anisotropic spectral properties of the QD assembly. The spatial orientation of the aggregates is selectively controlled in situ by the application of in-plane electric fields. The strong interdot coupling further increases the excitonic recombination rate which is both direction and electric field dependent. This electrical modulation, a noninvasive process, could potentially be an important functionality for the design and creation of building blocks for novel optoelectronic devices.

The design and development of multifunctional composite materials from artificial nano-constituents is one of the most compelling current research areas. This drive to improve over nature and produce 'meta-materials' has met with some success, but results have proven limited with regards to both the demonstration of synergistic functionalities and in the ability to manipulate the material properties post-fabrication and in situ. Here, magnetic nanoparticles (MNPs) and semiconducting quantum dots (QDs) are co-assembled in a nematic liquid crystalline (LC) matrix, forming composite structures in which the emission intensity of the quantum dots is systematically and reversibly controlled with a small applied magnetic field (<100 mT). This magnetic field-driven brightening, ranging between a two- to three-fold peak intensity increase, is a truly cooperative effect: the LC phase transition creates the co-assemblies, the clustering of the MNPs produces LC re-orientation at atypical low external field, and this re-arrangement produces compaction of the clusters, resulting in the detection of increased QD emission. These results demonstrate a synergistic, reversible, and an all-optical process to detect magnetic fields and additionally, as the clusters are self-assembled in a fluid medium, they offer the possibility for these sensors to be used in broad ranging fluid-based applications.

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