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Thermogenetics is a promising neuromodulation technique based on the use of heat-sensitive ion channels. However, on the way to its clinical application, a number of questions have to be addressed. First, to avoid immune response in future human applications, human ion channels should be studied as thermogenetic actuators. Second, heating levels necessary to activate these channels in vivo in brain tissue should be studied and cytotoxicity of these temperatures addressed. Third, the possibility and safety of chronic neuromodulation has to be demonstrated. In this study, we present a comprehensive framework for thermogenetic neuromodulation in vivo using the thermosensitive human ion channel hTRPV1. By targeting hTRPV1 expression to excitatory neurons of the mouse brain and activating them within a non-harmful temperature range with a fiber-coupled infrared laser, we not only induced neuronal firing and stimulated locomotion in mice, but also demonstrated that thermogenetics can be employed for repeated neuromodulation without causing evident brain tissue injury. Our results lay the foundation for the use of thermogenetic neuromodulation in brain research and therapy of neuropathologies., (© 2024. The Author(s).)

Statistics of self-focusing induced by a stochastic laser driver is shown to converge, in the large-sample-size limit, to a generalized Poisson distribution whose mean is given by the exponent of the respective extreme-value statistics. For a given ratio of the laser peak power to the self-focusing threshold P cr , the mean number of self-focusing counts in a large sample of laser pulses is shown to depend on the number of pulses in the sample, N, and the signal-to-noise ratio of laser pulses, a. We derive a closed-form solution for the threshold of stochastic self-focusing, which, unlike its deterministic counterpart, P cr , is a function of the sample size N and the signal-to-noise ratio a. The parameter N a  = exp (a 2 /2) is shown to set a borderline between the deterministic and stochastic regimes of self-focusing. When the number of laser pulses in a sample becomes comparable to N a , self-focusing can no longer be viewed as deterministic even for high signal-to-noise laser beams.

We show that, although nonlinear optics may give rise to a vast multitude of statistics, all these statistics converge, in their extreme-value limit, to one of a few universal extreme-value statistics. Specifically, in the class of polynomial nonlinearities, such as those found in the Kerr effect, weak-field harmonic generation, and multiphoton ionization, the statistics of the nonlinear-optical output converges, in the extreme-value limit, to the exponentially tailed, Gumbel distribution. Exponentially growing nonlinear signals, on the other hand, such as those induced by parametric instabilities and stimulated scattering, are shown to reach their extreme-value limits in the class of the Fréchet statistics, giving rise to extreme-value distributions (EVDs) with heavy, manifestly nonexponential tails, thus favoring extreme-event outcomes and rogue-wave buildup.

Rapidly progressing laser technologies provide powerful tools to study potential barrier-passage dynamics in physical, chemical, and biological systems with unprecedented temporal and spatial resolution and a remarkable chemical and structural specificity. The available theories of barrier passage, however, operate with equations, potentials, and parameters that are best suited for a specific area of research and a specific class of systems and processes. Making connections among these theories is often anything but easy. Here, we address this problem by presenting a unified framework for the description of a vast variety of classical and quantum barrier-passage phenomena, revealing an innate connection between various types of barrier-passage dynamics and providing closed-form equations showing how the signature exponentials in classical and quantum barrier-passage rates relate to and translate into each other. In this framework, the Arrhenius-law kinetics, the emergence of the Gibbs distribution, Hund's molecular wave-packet well-to-well oscillatory dynamics, Keldysh photoionization, and Kramers' escape over a potential barrier are all understood as manifestations of a potential-driven Markovian dynamics whereby a system evolves from a state of local stability. Key to the irreducibility of quantum tunneling to thermally activated barrier passage is the difference in the ways the diffusion-driving potentials emerge in these two tunneling settings, giving rise to stationary states with a distinctly different structure.

The notion of the first passage time is shown to offer a meaningful extension to quantum tunneling, providing a closed-integral-form analytical unification of the tunneling rate and the tunneling passage time. We demonstrate that, in suitable potential settings, the quantum first passage time, found as a solution to the Fokker-Planck and backward Kolmogorov's equations for the quantum probability density, recovers the hallmark results for the Kramers escape rate, the lifetime of tunneling quasi-stationary wave packets, leads to a classical, distance-over-speed passage time for a free-particle wave function, and offers useful insights into Keldysh's intimation on the electron barrier-traversal time in field-induced ionization.

We examine the spatial modulation instability (MI) of a partially incoherent laser beam. We show that the P < (a/r c ) 2 P 0 criterion of beam stability, with a laser peak power P, beam radius a, correlation radius r c , and critical power of self-focusing P 0 , is applicable only to a limited class of MIs, viz., MIs that can be described as instabilities of a pertinent transverse correlation function found as a solution to the evolution equation, where the expectation of the four-field-product nonlinear source term is factorized as a product of the field intensity and a two-point transverse correlation function. When extended to a more general class of MIs, field evolution analysis of partially coherent beams suggests that MIs can be attenuated, but never completely suppressed. We show that spatial incoherence can lower the MI-buildup rate, thus helping avoid MI-induced beam breakup in physical settings where the MI-buildup length l MI can be kept longer than the length of the nonlinear medium L. Because the l MI  > L condition sets a limitation on the field intensity rather than the laser peak power, MI-induced beam breakup can be avoided, even at laser peak powers well above the critical power of self-focusing P 0 .

Diabetes is one of the significant risk factors for ischemic stroke. Hyperglycemia exacerbates the pathogenesis of stroke, leading to more extensive cerebral damage and, as a result, to more severe consequences. However, the mechanism whereby the hyperglycemic status in diabetes affects biochemical processes during the development of ischemic injury is still not fully understood. In the present work, we record for the first time the real-time dynamics of H 2 O 2 in the matrix of neuronal mitochondria in vitro in culture and in vivo in the brain tissues of rats during development of ischemic stroke under conditions of hyperglycemia and normal glucose levels. To accomplish this, we used a highly sensitive HyPer7 biosensor and a fiber-optic interface technology. We demonstrated that a high glycemic status does not affect the generation of H 2 O 2 in the tissues of the ischemic core, while significantly exacerbating the consequences of pathogenesis. For the first time using Raman microspectroscopy approach, we have shown how a sharp increase in the blood glucose level increases the relative amount of reduced cytochromes in the mitochondrial electron transport chain in neurons under normal conditions in awake mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We demonstrate how the Hong-Ou-Mandel (HOM) interference with polarization-entangled photons can be used to probe ultrafast dephasing. We can infer the optical properties like the real and imaginary parts of the complex susceptibility of the medium from changes in the position and the shape of the HOM dip. From the shift of the HOM dip, we are able to measure 22 fs dephasing time using a continuous-wave (CW) laser even with optical loss > 97 %, while the HOM dip visibility is maintained at 92.3 % (which can be as high as 96.7 %). The experimental observations, which are explained in terms of a rigorous theoretical model, demonstrate the utility of HOM interference in probing ultrafast dephasing.

We present an experimental framework and methodology for in vivo studies on rat stroke models that enable a real-time fiber-optic recording of stroke-induced hydrogen peroxide and pH transients in ischemia-affected brain areas. Arrays of reconnectable implantable fiber probes combined with advanced optogenetic fluorescent protein sensors are shown to enable a quantitative multisite time-resolved study of oxidative-stress and acidosis buildup dynamics as the key markers, correlates and possible drivers of ischemic stroke. The fiber probes designed for this work provide a wavelength-multiplex forward-propagation channel for a spatially localized, dual-pathway excitation of genetically encoded fluorescence-protein sensors along with a back-propagation channel for the fluorescence return from optically driven fluorescence sensors. We show that the spectral analysis of the fiber-probe-collected fluorescence return provides means for a high-fidelity autofluorescence background subtraction, thus enhancing the sensitivity of real-time detection of stroke-induced transients and significantly reducing measurement uncertainties in in vivo acute-stroke studies as inherently statistical experiments operating with outcomes of multiply repeated measurements on large populations of individually variable animal stroke models., (© 2022 Wiley-VCH GmbH.)

We demonstrate a versatile framework for cellular brain imaging in awake mice based on suitably tailored segments of graded-index (GRIN) fiber. Closed-form solutions to ray-path equations for graded-index waveguides are shown to offer important insights into image-transmission properties of GRIN fibers, suggesting useful recipes for optimized GRIN-fiber-based deep-brain imaging. We show that the lengths of GRIN imaging components intended for deep-brain studies in freely moving rodents need to be chosen as a tradeoff among the spatial resolution, the targeted imaging depth and the degree of fiber-probe invasiveness. In the experimental setting that we present in this paper, the head of an awake mouse with a GRIN-fiber implant is fixed under a microscope objective, but the mouse is free to move around an in-house-built flat-floored air-lifted platform, exploring a predesigned environment, configured as an arena for one of standard cognitive tests. We show that cellular-resolution deep-brain imaging can be integrated in this setting with robust cell-specific optical neural recording to enable in vivo studies with minimal physical restraints on animal models. The enhancement of the information capacity of the fluorescence signal, achieved via a suitable filtering of the GRIN-fiber readout, is shown to open routes toward practical imaging modalities whereby the deep-brain neuronal dynamics and axonal connections underpinning the integrative functions of essential brain structures can be studied in awake rodent models., (© 2022 Wiley-VCH GmbH.)

We present a particle-in-cell (PIC) analysis of terahertz (THz) radiation by ultrafast plasma currents driven by relativistic-intensity laser pulses. We show that, while the I 0 [Formula: see text] product of the laser intensity I 0 and the laser wavelength λ 0 plays the key role in the energy scaling of strong-field laser-plasma THz generation, the THz output energy, W THz , does not follow the I 0 [Formula: see text] scaling. Its behavior as a function of I 0 and λ 0 is instead much more complex. Our two- and three-dimensional PIC analysis shows that, for moderate, subrelativistic and weakly relativistic fields, W THz (I 0 [Formula: see text]) can be approximated as (I 0 λ 0 2 ) α , with a suitable exponent α, as a clear signature of vacuum electron acceleration as a predominant physical mechanism whereby the energy of the laser driver is transferred to THz radiation. For strongly relativistic laser fields, on the other hand, W THz (I 0 [Formula: see text]) closely follows the scaling dictated by the relativistic electron laser ponderomotive potential [Formula: see text], converging to W THz ∝ [Formula: see text] for very high I 0 , thus indicating the decisive role of relativistic ponderomotive charge acceleration as a mechanism behind laser-to-THz energy conversion. Analysis of the electron distribution function shows that the temperature T e of hot laser-driven electrons bouncing back and forth between the plasma boundaries displays the same behavior as a function of I 0 and λ 0 , altering its scaling from (I 0 λ 0 2 ) α to that of [Formula: see text], converging to W THz ∝ [Formula: see text] for very high I 0 . These findings provide a clear physical picture of THz generation in relativistic and subrelativistic laser plasmas, suggesting the THz yield W THz resolved as a function of I 0 and λ 0 as a meaningful measurable that can serve as a probe for the temperature T e of hot electrons in a vast class of laser-plasma interactions. Specifically, the α exponent of the best (I 0 λ 0 2 ) α fit of the THz yield suggests a meaningful probe that can help identify the dominant physical mechanisms whereby the energy of the laser field is converted to the energy of plasma electrons., (© 2022. The Author(s).)

We examine the state-vector geometry and guided-wave physics underpinning spatial super-resolution, which can be attained in far-field linear microscopy via a combination of statistical analysis, quantum optics, and spatial mode demultiplexing. A suitably tailored guided-wave signal pickup is shown to provide an information channel that can distill the super-resolving spatial modes, thus enabling an estimation of sub-Rayleigh space intervals ξ. We derive closed-form analytical expressions describing the distribution of the ξ-estimation Fisher information over waveguide modes, showing that this information remains nonvanishing as ξ → 0, thus preventing the variance of ξ estimation from diverging at ξ → 0. We demonstrate that the transverse refractive index profile n Q (r) tailored to support the optimal wave function ψ Q (r) for super-resolving ξ estimation encodes the same information about ξ as the entire manifold of waveguide modes needed to represent ψ Q (r). Unlike ψ Q (r), n Q (r) does not need a representation in a lengthy manifold of eigenmodes and can be found instead via adaptive feedback-controlled learning.

We identify the physical factors that limit the terahertz (THz) yield of an optical rectification (OR) of ultrashort multiterawatt laser pulses in large-area quadratically nonlinear crystals. We show that the THz yield tends to slow its growth as a function of the laser driver energy, saturate, and eventually decrease as the laser beam picks up a spatiotemporal phase due to the intensity-dependent refraction of the OR crystal. We demonstrate that, with a careful management of the driver intensity aimed at keeping the nonlinear length larger than the coherence length, OR-based broadband THz generation in large-area lithium niobate (LN) crystals is energy-scalable, enabling an OR of multiterawatt laser pulses, yielding ∼10µ J / c m 2 of THz output energy per unit crystal area. With a 27-fs, 10-TW, 800-nm Ti:sapphire laser output used as a driver for OR in large-area LN crystals, this approach is shown to provide a THz output with a pulse energy above 10 µJ and a bandwidth extending well beyond 6 THz, supporting single-cycle THz waveforms.

Enhanced-resolution imaging in complex scattering media is revisited from a parameter estimation perspective. A suitably defined Fisher information is shown to offer useful insights into the limiting precision of parameter estimation in a scattering environment and, hence, into the limiting spatial resolution that can be achieved in imaging-through-scattering settings. The Fisher information that defines this resolution limit via the Cramér-Rao lower bound is shown to scale with the number of adaptively controlled space-time modes of the probe field, suggesting a physically intuitive generalization of the Abbe limit to the spatial resolution attainable for complex scattering systems. In a conventional, direct-imaging microscopy setting, this bound is shown to converge to the canonical Abbe limit.

Ischemic cerebral stroke is one of the leading causes of death and disability in humans. However, molecular processes underlying the development of this pathology remain poorly understood. There are major gaps in our understanding of metabolic changes that occur in the brain tissue during the early stages of ischemia and reperfusion. In particular, it is generally accepted that both ischemia (I) and reperfusion (R) generate reactive oxygen species (ROS) that cause oxidative stress which is one of the main drivers of the pathology, although ROS generation during I/R was never demonstrated in vivo due to the lack of suitable methods. In the present study, we record for the first time the dynamics of intracellular pH and H 2 O 2 during I/R in cultured neurons and during experimental stroke in rats using the latest generation of genetically encoded biosensors SypHer3s and HyPer7. We detect a buildup of powerful acidosis in the brain tissue that overlaps with the ischemic core from the first seconds of pathogenesis. At the same time, no significant H 2 O 2 generation was found in the acute phase of ischemia/reperfusion. HyPer7 oxidation in the brain was detected only 24 h later. Comparison of in vivo experiments with studies on cultured neurons under I/R demonstrates that the dynamics of metabolic processes in these models significantly differ, suggesting that a cell culture is a poor predictor of metabolic events in vivo., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Secondary radiation emission of laser-induced filaments is revisited from a perspective of transient antenna radiation. Solutions for transient-antenna radiation fields are shown to provide an accurate description of the spectral and polarization properties, radiation patterns, and the angular dispersion of terahertz and microwave radiation emitted by laser filaments. Time-domain pulsed-antenna analysis offers a physically clear explanation for the bandwidth of this radiation, relating the low-frequency cutoff in its spectrum to the filament length, thus explaining efficient microwave generation in laser filamentation experiments.

Multimodal nonlinear microscopy combining third-harmonic generation (THG) with two- and three-photon-excited fluorescence (2PEF and 3PEF) is shown to provide a powerful resource for high-fidelity imaging of nucleoli and nucleolar proteins. We demonstrate that, with a suitably tailored genetically encoded fluorescent stain, the 2PEF/3PEF readout from specific nucleolar proteins can be reliably detected against the extranucleolar 2PEF/3PEF signal, enabling high-contrast imaging of the key nucleolar ribosome biogenesis components, such as fibrillarin. THG is shown to provide a versatile readout for unstained nucleolus imaging in a vast class of biological systems as different as neurons in brain slices and cultured HeLa cells.

Spectral analysis of high-order harmonics generated by ultrashort mid-infrared pulses in molecular nitrogen reveals well-resolved signatures of inverse Raman scattering, showing up near the frequencies of prominent vibrational transitions of nitrogen molecules. When tuned on a resonance with the v ' =0→ v ' ' =0 pathway within the B 3 Π g → C 3 Π u second positive system of molecular nitrogen, the eleventh harmonic of a 3.9 µm, 80 fs driver is shown to acquire a distinctive antisymmetric spectral profile with red-shifted bright and blue-shifted dark features as indicators of stimulated Raman gain and loss. This high-harmonic setting extends the inverse Raman effect to a vast class of strong-field light-matter interaction scenarios.

Cutting-edge methods of laser microscopy combined with fluorescent protein engineering and spectral analysis provide a unique resource for high-resolution neuroimaging, enabling a high-fidelity, high-contrast detection of fine structural details of neural cells and intracellular compartments. In addition to their extraordinary imaging abilities in real space, such methods can help resolve the neural states in a multidimensional space of neural responses whereby individual neurons and neural populations encode information on external stimuli. This study shows, however, that laser-induced biochemical processes in neural cells can give rise to an uncertainty of neural states, setting an upper bound on the information that optical measurements can provide on neural states, neural encodings, and neural dynamics. Comparison of absorbed laser power with the native biochemical energy budget of neuronal firing suggests that each readout photon in optical recording comes at a cost of precision of neural encoding and a loss of information encoded by the neural response. A quantitative measure for such a measurement-induced neural uncertainty can be defined, as this study shows, in terms of the Fisher information, relating the lower bound of this uncertainty to the loss of the Shannon information capacity of neural states., Competing Interests: Declaration of Competing Interest The author declares no financial or commercial conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We propose to enhance the performance of localized plasmon structured illumination microscopy (LP-SIM) via intensity correlations. LP-SIM uses sub-wavelength illumination patterns to encode high spatial frequency information. It can enhance the resolution up to three-fold before gaps in the optical transfer function (OTF) support arise. For blinking fluorophores or for quantum antibunching, an intensity correlation analysis induces higher harmonics of the illumination pattern and enlarges the effective OTF. This enables ultrahigh resolutions without gaps in the OTF support, and thus a fully deterministic imaging scheme. We present simulations that include shot and external noise and demonstrate the resolution power under realistic photon budgets. The technique has potential in light microscopy where low-intensity illumination is paramount while aiming for high spatial but moderate temporal resolutions.

We revisit the energy-time uncertainty underpinning of the pointwise bounds of laser-driven ionization dynamics. When resolved within the driver pulse and its field cycle, these bounds are shown to manifest the key signature tendencies of photoionization current dynamics-a smooth growth within the pulse in the regime of multiphoton ionization and an abrupt, almost stepwise photocurrent buildup within a fraction of the field cycle in the limit of tunneling ionization. In both regimes, the Keldysh time, defined as the ratio of the Keldysh parameter to the driver frequency, serves as a benchmark for the minimum time of photoionization, setting an upper bound for the photoelectron current buildup rate.

Ultrafast ionization of a gas medium driven by ultrashort midinfrared laser pulses provides a source of bright ultrabroadband radiation whose spectrum spans across the entire microwave band, reaching for the sub-gigahertz range. We combine multiple, mutually complementary detection techniques to provide an accurate polarization-resolved characterization of this broadband output as a function of the gas pressure. At low gas pressures, the lowest-frequency part of this output is found to exhibit a drastic enhancement as this field builds up its coherence, developing a well-resolved emission cone, dominated by a radial radiation energy flux. This behavior of the intensity, coherence, and polarization of the microwave output is shown to be consistent with Cherenkov-type radiation by ponderomotively driven plasma currents.

We present experiments on cell cultures and brain slices that demonstrate two-photon optogenetic pH sensing and pH-resolved brain imaging using a laser driver whose spectrum is carefully tailored to provide the maximum contrast of a ratiometric two-photon fluorescence readout from a high-brightness genetically encoded yellow-fluorescent-protein-based sensor, SypHer3s. Two spectrally isolated components of this laser field are set to induce two-photon-excited fluorescence (2PEF) by driving SypHer3s through one of two excitation pathways-via either the protonated or deprotonated states of its chromophore. With the spectrum of the laser field accurately adjusted for a maximum contrast of these two 2PEF signals, the ratio of their intensities is shown to provide a remarkably broad dynamic range for pH measurements, enabling high-contrast optogenetic deep-brain pH sensing and pH-resolved 2PEF imaging within a vast class of biological systems, ranging from cell cultures to the living brain., (© 2020 Wiley-VCH GmbH.)

We demonstrate a reconnectable implantable ultraslim fiber-optic microendoscope that integrates a branching fiber bundle (BFB) with gradient-index fiber lenses, enabling a simultaneous fluorescence imaging of individual cells in distinctly separate brain regions, including brain structures as distant as the neocortex and hippocampus. We show that fluorescence images of individual calcium-indicator-expressing neurons in the brain of freely moving transgenic mice can be recorded, via the implanted BFB probe, in parallel with time- and cell-resolved traces of calcium signaling, thus enabling correlated circuit-dynamics studies at -multiple sites within the brain of freely moving animals., (© 2020 Wiley-VCH GmbH.)

We show that waveguide sensors can enable a quantitative characterization of coronavirus spike glycoprotein-host-receptor binding-the process whereby coronaviruses enter human cells, causing disease. We demonstrate that such sensors can help quantify and eventually understand kinetic and thermodynamic properties of viruses that control their affinity to targeted cells, which is known to significantly vary in the course of virus evolution, e.g., from SARS-CoV to SARS-CoV-2, making the development of virus-specific drugs and vaccine difficult. With the binding rate constants and thermodynamic parameters as suggested by the latest SARS-CoV-2 research, optical sensors of SARS-CoV-2 spike protein-receptor binding may be within sight.

We identify an unusual regime of ultrafast nonlinear dynamics in which an optical shock wave couples to soliton self-compression, steepening the tail of the pulse, thus yielding self-compressing soliton transients as short as the field sub-half-cycle. We demonstrate that this extreme pulse self-compression scenario can help generate sub-half-cycle mid-infrared pulses in a broad class of anomalously dispersive optical waveguide systems.

At the level of peak powers needed for a Kerr-lens mode-locked operation of solid-state soliton short-pulse lasers, a periodic perturbation induced by spatially localized pulse amplification in a laser cavity can induce soliton instability with respect to resonant dispersive-wave radiation, eventually leading to soliton blowup and pulse splitting of the laser output. Here, we present an experimental study of a high-peak-power self-mode-locking Cr:forsterite laser, showing that, despite its complex, explosion-like buildup dynamics, this soliton blowup can be captured and quantitatively characterized via an accurate cavity-dispersion- and gain-resolved analysis of the laser output. We demonstrate that, with a suitable cavity design and finely tailored balance of gain, dispersion, and nonlinearity, such a laser can be operated in a subcritical mode, right beneath the soliton blowup threshold, providing an efficient source of sub-100-fs 15-20 MHz repetition-rate pulses with energies as high as 33 nJ.

We demonstrate an accurate quantitative characterization of absolute two- and three-photon absorption (2PA and 3PA) action cross sections of a genetically encodable fluorescent marker Sypher3s. Both 2PA and 3PA action cross sections of this marker are found to be remarkably high, enabling high-brightness, cell-specific two- and three-photon fluorescence brain imaging. Brain imaging experiments on sliced samples of rat's cortical areas are presented to demonstrate these imaging modalities. The 2PA action cross section of Sypher3s is shown to be highly sensitive to the level of pH, enabling pH measurements via a ratiometric readout of the two-photon fluorescence with two laser excitation wavelengths, thus paving the way toward fast optical pH sensing in deep-tissue experiments., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We present brain imaging experiments on rat cortical areas, demonstrating that, when combined with a suitable high-brightness, cell-specific genetically encoded fluorescent marker, three-photon-excited fluorescence (3PEF), enables subcellular-resolution, cell-specific 3D brain imaging that is fully compatible and readily integrable with other nonlinear-optical imaging modalities, including two-photon-fluorescence and harmonic-generation microscopy. With laser excitation provided by sub-100-fs, 1.25-µm laser pulses, cell-specific 3PEF from astrocytes and their processes detected in parallel with a three-photon-resonance-enhanced third harmonic from blood vessels is shown to enable a high-contrast 3D imaging of gliovascular interfaces.

Coherent-wake plasma emission induced by ultrashort mid-infrared laser pulses on a solid target is shown to give rise to high-brightness, high-order harmonic radiation, offering a promising source of attosecond pulses and a probe for ultrafast subrelativistic plasma dynamics. With 80-fs, 0.2-TW pulses of 3.9-μm radiation used as a driver, optical harmonics up to the 34th order are detected, with their spectra stretching from the mid-infrared region to the extreme ultraviolet region. The harmonic spectrum is found to be highly sensitive to the chirp of the driver. Particle-in-cell analysis of this effect suggests, in agreement with the generic scenario of coherent-wake emission, that optical harmonics are radiated as trains of extremely short, attosecond ultraviolet pulses with a pulse-to-pulse interval varying over the pulse train. A positive chirp of the driver pulse can partially compensate for this variation in the interpulse separation, allowing harmonics of the highest orders to be generated in the plasma emission spectrum.

A harmonically driven cavity QED system consisting of two cavities and a two-level qubit is shown to enable the generation of a vast class of maximally entangled states suitable for measurements with a Heisenberg-limit precision. As one of its modalities, this system can serve as a quantum beam splitter, converting an |N〉 ⊗ |0〉 input into a maximally entangled N00N state (|N〉 ⊗ |0〉  +  |0〉 ⊗ |N〉)/[Formula: see text] at its output. A network of such quantum beam splitters is shown to provide a source of multimode N00N-type entanglement.

Methods of nonlinear optics provide a vast arsenal of tools for label-free brain imaging, offering a unique combination of chemical specificity, the ability to detect fine morphological features, and an unprecedentedly high, subdiffraction spatial resolution. While these techniques provide a rapidly growing platform for the microscopy of neurons and fine intraneural structures, optical imaging of astroglia still largely relies on filament-protein-antibody staining, subject to limitations and difficulties especially severe in live-brain studies. Once viewed as an ancillary, inert brain scaffold, astroglia are being promoted, as a part of an ongoing paradigm shift in neurosciences, into the role of a key active agent of intercellular communication and information processing, playing a significant role in brain functioning under normal and pathological conditions. Here, we show that methods of nonlinear optics provide a unique resource to address long-standing challenges in label-free astroglia imaging. We demonstrate that, with a suitable beam-focusing geometry and careful driver-pulse compression, microscopy of second-harmonic generation (SHG) can enable a high-resolution label-free imaging of fibrillar structures of astrocytes, most notably astrocyte processes and their endfeet. SHG microscopy of astrocytes is integrated in our approach with nonlinear-optical imaging of red blood cells based on third-harmonic generation (THG) enhanced by a three-photon resonance with the Soret band of hemoglobin. With astroglia and red blood cells providing two physically distinct imaging contrasts in SHG and THG channels, a parallel detection of the second and third harmonics enables a high-contrast, high-resolution, stain-free stereoimaging of gliovascular interfaces in the central nervous system. Transverse scans of the second and third harmonics are shown to resolve an ultrafine texture of blood-vessel walls and astrocyte-process endfeet on gliovascular interfaces with a spatial resolution within 1 μm at focusing depths up to 20 μm inside a brain., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We demonstrate that a background-free readout of two-photon fluorescence from nitrogen-vacancy (NV) centers in a strongly fluorescing environment can be accomplished by all-optical means via a multiphoton charge-state modulation of NV centers in a mixture of negatively charged and neutral NV centers. A 100 fs, 1060 nm output of an ytterbium fiber laser is ideally suited for this modality of multiphoton microscopy, providing, as our experiments show, an efficient two-photon excitation of both NV - and NV 0 charge states, but keeping the nonlinearity of n-photon ionization needed for NV - /NV 0 charge-state modulation to a minimum, n=3.

We demonstrate stain-free, high-contrast, subcellular-resolution imaging of astroglial cells using epi-detected third-harmonic generation (THG). The astrocyte-imaging capability of THG is verified by colocalizing THG images with fluorescence images of astrocytes expressing a genetically encodable fluorescent reporter. We show that THG imaging with an optimized point-spread function can reliably detect significant subcellular features of astrocytes, including cell nuclei, as well as the soma shape and boundaries.

Analysis of the complex refractive index of atmospheric air reveals remarkably broad and continuous regions of anomalous and near-zero group-velocity dispersion in the subterahertz (sub-THz) and millimeter-band atmospheric windows. One such broadband dispersion anomaly is shown to occur in the high-frequency wing of the 60-GHz band of molecular oxygen. Adjacent to this dispersion anomaly is a broadband atmospheric transparency region within which the group-velocity dispersion is unusually weak, enabling distortion-free long-distance transmission of broadband millimeter-wave field waveforms, as well as broadband remote sensing in the millimeter band. Although broad regions of anomalous and near-zero dispersion also exist in the sub-THz range, their utility for long-distance transmission and remote sensing is limited because of strong atmospheric absorption.

We present one- and two-photon-absorption fluorescence spectroscopic analysis of biliverdin (BV) chromophore-based single-domain near-infrared fluorescent proteins (iRFPs). The results of these studies are used to estimate the internal electric fields acting on BV inside iRFPs and quantify the electric dipole properties of this chromophore, defining the red shift of excitation and emission spectra of BV-based iRFPs. The iRFP studied in this work is shown to fit well the global diagram of the red-shift tunability of currently available BV-based iRFPs as dictated by the quadratic Stark effect, suggesting the existence of the lower bound for the strongest red shifts attainable within this family of fluorescent proteins. The absolute value of the two-photon absorption (TPA) cross section of a fluorescent calcium sensor based on the studied iRFP is found to be significantly larger than the TPA cross sections of other widely used genetically encodable fluorescent calcium sensors., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Formation of light bullets-tightly localized in space and time light packets, retaining their spatiotemporal shape during propagation-is, for the first time, experimentally observed and investigated in a new regime of mid-infrared filamentation in ambient air. It is suggested that the light bullets generated in ambient air by multi-mJ, positively chirped 3.9-μm pulses originate from a dynamic interplay between the anomalous dispersion in the vicinity of CO 2 resonance and positive chirp, both intrinsic, carried by the driver pulse, and accumulated, originating from nonlinear propagation in air. By adjusting the initial chirp of the driving pulses, one can control the spatial beam profile, energy losses, and spectral-temporal dynamics of filamenting pulses and deliver sub-3-cycle mid-IR pulses in high-quality beam on a remote target.

Polarization maps of high-order harmonics are shown to enable a full vectorial characterization of petahertz electron currents generated in a crystalline solid by an ultrashort laser driver. As a powerful resource of this methodology, analysis of energy-momentum dispersion landscapes, defined by the electron band structure, can help identify, as our analysis shows, special directions within the Brillouin zone that can provide a preferable basis for polarization-sensitive high-harmonic mapping of anisotropic petahertz photocurrents in solids.

We derive a closed-form analytical expression for the linear entropy of a multipartite qutrit state, providing a quantitative measure for quantum entanglement within the class of n-mode nonorthogonal qutrit states with any n. Conditions for enhanced and maximum quantum entanglement of multipartite qutrit states are identified. The usefulness of the introduced multipartite qutrit states as quantum communication channel resources is analyzed. The Hamiltonians allowing for the generation of multipartite qutrit states can be attained by combining optomechanical cavities with sequences of tunable beam splitters.

Thermogenetics is a promising innovative neurostimulation technique, which enables robust activation of single neurons using thermosensitive cation channels and IR stimulation. The main advantage of IR stimulation compared to conventional visible light optogenetics is the depth of penetration (up to millimeters). Due to physiological limitations, thermogenetic molecular tools for mammalian brain stimulation remain poorly developed. Here, we tested the possibility of employment of this new technique for stimulation of neocortical neurons. The method is based on activation gating of TRPV1-L channels selectively expressed in specific cells. Pyramidal neurons of layer 2/3 of neocortex were transfected at an embryonic stage using a pCAG expression vector and electroporation in utero. Depolarization and spiking responses of TRPV1L+ pyramidal neurons to IR radiation were recorded electrophysiologically in acute brain slices of adult animals with help of confocal visualization. As TRPV1L-expressing neurons are not sensitive to visible light, there were no limitations of the use of this technique with conventional fluorescence imaging. Our experiments demonstrated that the TRPV1-L+ pyramidal neurons preserve their electrical excitability in acute brain slices, while IR radiation can be successfully used to induce single neuronal depolarization and spiking at near physiological temperatures. Obtained results provide important information for adaptation of thermogenetic technology to mammalian brain studies in vivo., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We demonstrate free-beam spectral self-compression of ~100-GW femtosecond laser pulses due to self-phase modulation (SPM) in a transparent dielectric. While all the earlier studies of SPM-induced spectral narrowing have been performed using optical fibers, experiments and simulations presented in this Letter show that this type of spectral transformation can be implemented as a part of a full three-dimensional field-waveform dynamics and can be extended to peak powers ∼10 5 times higher than the critical power of self-focusing. With a properly chosen initial chirp, spectral self-compression is accompanied by pulse compression, providing spectral-temporal mode self-compression as a whole.

High-order harmonic generation (HHG) in plasmas induced by ultrashort, relativistic-intensity laser pulses on solid surfaces can provide an efficient source of attosecond pulses and opens routes toward new regimes of laser-matter interactions, x-ray generation, laser particle acceleration, and relativistic nonlinear optics. However, field intensities in the range of I rel ∼10 19   W/cm 2 are typically needed to achieve the relativistic regime of HHG in experiments with near-infrared laser pulses. Here, we show that, in the mid-infrared range, due to the λ -2 scaling of I rel with the driver wavelength λ, relativistic HHG can be observed at much lower levels of laser field intensities. High-peak-power 80-fs, 3.9-μm pulses are focused in our experiments on a solid surface to provide field intensities in the range of 10 17   W/cm 2 . Remarkably, this level of field intensities, considered as low by the standards of relativistic optics in the near infrared, is shown to be sufficient for generation of high-order harmonics with signature properties of relativistic HHG-beam directionality, spectra with extended plateaus, and a high HHG yield sustained for both p- and s-polarized driver fields.

The signal-to-noise contrast of the optical readout in broadband Raman quantum memories is analyzed as a function of the pulse widths and phase properties of tailored optical field waveforms used to write in and read out broadband photon wave packets. Based on this analysis, we quantify the tradeoff between the readout contrast and the speed of such memories. Off-resonance coherent four-wave mixing is shown to provide a source of noise photons, lowering the readout contrast in broadband Raman quantum memories. This noise cannot be suppressed by phase matching, but can be radically reduced with a suitable polarization arrangement and proper field-waveform tailoring.

A hybrid quantum device consisting of three ensembles of nitrogen-vacancy centers (NVEs) whose spins are collectively coupled to a superconducting coplanar waveguide resonator is shown to enable the generation of controllable tripartite macroscopic entangled states. The density matrix of such NVEs can be encoded to recast a three-qubit system state, which can be characterized in terms of the entanglement witnesses in relation to the Greenberger-Horne-Zeilinger (GHZ) states. We identify the parameter space within which the generated entangled states can have an arbitrarily large overlap with GHZ states, indicating an enhanced entanglement in the system.