Neurophotonics

SIGNIFICANCE: Bioluminescent optogenetics (BL-OG) offers a unique and powerful approach to manipulate neural activity both opto- and chemogenetically using a single actuator molecule (a LuMinOpsin, LMO). AIM: To further enhance the utility of BL-OG by improving the efficacy of chemogenetic (bioluminescence-driven) LMO activation. APPROACH: We developed novel luciferases optimized for Förster resonance energy transfer when fused to the fluorescent protein mNeonGreen, generating bright bioluminescent (BL) emitters spectrally tuned to Volvox Channelrhodopsin 1 (VChR1)...

Bioluminescence is a popular modality for imaging in living organisms. The platform relies on enzymatically (luciferase) generated light via the oxidation of small molecule luciferins. Since no external light is needed for photon production, there are no concerns with background autofluorescence or photobleaching over time-features that have historically limited other optical readouts. Bioluminescence is thus routinely used for longitudinal tracking across whole animals. Applications in the brain, though, have been more challenging due to a lack of sufficiently bioavailable, bright, and easily multiplexed probes...

The use of bioluminescence as a reporter for physiology in neuroscience is as old as the discovery of the calcium-dependent photon emission of aequorin. Over the years, luciferases have been largely replaced by fluorescent reporters, but recently, the field has seen a renaissance of bioluminescent probes, catalyzed by unique developments in imaging technology, bioengineering, and biochemistry to produce luciferases with previously unseen colors and intensity. This is not surprising as the advantages of bioluminescence make luciferases very attractive for noninvasive, longitudinal in vivo observations without the need of an excitation light source...

SIGNIFICANCE: Intravital cellular calcium imaging has emerged as a powerful tool to investigate how different types of neurons interact at the microcircuit level to produce seizure activity, with newfound potential to understand epilepsy. Although many methods exist to measure seizure-related activity in traditional electrophysiology, few yet exist for calcium imaging. AIM: To demonstrate an automated algorithmic framework to detect seizure-related events using calcium imaging-including the detection of pre-ictal spike events, propagation of the seizure wavefront, and terminal spreading waves for both population-level activity and that of individual cells...

SIGNIFICANCE: Efforts starting more than 20 years ago led to increasingly well performing genetically encoded voltage indicators (GEVIs) for optical imaging at wavelengths <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo><</mml:mo><mml:mn>600</mml:mn><mml:mtext>  </mml:mtext><mml:mi>nm</mml:mi></mml:mrow></mml:math>. Although optical imaging in the <mml:math xmlns:mml="https://www...

The editorial presents the two-part Special Section on Frontiers in Neurophotonics.

The Frontiers in Neurophotonics Symposium is a biennial event that brings together neurobiologists and physicists/engineers who share interest in the development of leading-edge photonics-based approaches to understand and manipulate the nervous system, from its individual molecular components to complex networks in the intact brain. In this Community paper, we highlight several topics that have been featured at the symposium that took place in October 2022 in Québec City, Canada.

SIGNIFICANCE: Prefrontal cortex (PFC) hemodynamics are regulated by numerous underlying neurophysiological components over multiple temporal scales. The pattern of output signals, such as functional near-infrared spectroscopy fluctuations (i.e., fNIRS), is thus complex. We demonstrate first-of-its-kind evidence that this fNIRS complexity is a marker that captures the influence of endurance capacity and the effects of hydrogen gas (<mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>H</mml:mi><mml:mn>2</mml:mn></mml:msub></mml:mrow></mml:math>) on PFC regulation...

Imaging neuronal architecture has been a recurrent challenge over the years, and the localization of synaptic proteins is a frequent challenge in neuroscience. To quantitatively detect and analyze the structure of synapses, we recently developed free SODA software to detect the association of pre and postsynaptic proteins. To fully take advantage of spatial distribution analysis in complex cells, such as neurons, we also selected some new dyes for plasma membrane labeling. Using Icy SODA plugin, we could detect and analyze synaptic association in both conventional and single molecule localization microscopy, giving access to a molecular map at the nanoscale level...

SIGNIFICANCE: The development of imaging systems that are cost-efficient and modular is essential for modern neuroscience research. AIM: In the current study, we designed, developed, and characterized a low-cost reversible tandem lens mesoscope for brain imaging in rodents. APPROACH: Using readily available components, we assembled a robust imaging system that is highly efficient and cost-effective. We developed a mesoscope that offers high-resolution structural and functional imaging with cost-effective lenses and CMOS camera...

SIGNIFICANCE: Bedside cerebral blood flow (CBF) monitoring has the potential to inform and improve care for acute neurologic diseases, but technical challenges limit the use of existing techniques in clinical practice. AIM: Here, we validate the Openwater optical system, a novel wearable headset that uses laser speckle contrast to monitor microvascular hemodynamics. APPROACH: We monitored 25 healthy adults with the Openwater system and concurrent transcranial Doppler (TCD) while performing a breath-hold maneuver to increase CBF...

SIGNIFICANCE: Fiber photometry (FP) is a widely used technique in modern behavioral neuroscience, employing genetically encoded fluorescent sensors to monitor neural activity and neurotransmitter release in awake-behaving animals. However, analyzing photometry data can be both laborious and time-consuming. AIM: We propose the fiber photometry analysis (FiPhA) app, which is a general-purpose FP analysis application. The goal is to develop a pipeline suitable for a wide range of photometry approaches, including spectrally resolved, camera-based, and lock-in demodulation...

The brain-based assessments under anesthesia have provided the ability to evaluate pain/nociception during surgery and the potential to prevent long-term evolution of chronic pain. Prior studies have shown that the functional near-infrared spectroscopy (fNIRS)-measured changes in cortical regions such as the primary somatosensory and the polar frontal cortices show consistent response to evoked and ongoing pain in awake, sedated, and anesthetized patients. We take this basic approach and integrate it into a potential framework that could provide real-time measures of pain/nociception during the peri-surgical period...

SIGNIFICANCE: An array of techniques for targeted neuromodulation is emerging, with high potential in brain research and therapy. Calcium imaging or other forms of functional fluorescence imaging are central solutions for monitoring cortical neural responses to targeted neuromodulation, but often are confounded by thermal effects that are inter-mixed with neural responses. AIM: Here, we develop and demonstrate a method for effectively suppressing fluorescent thermal transients from calcium responses...

SIGNIFICANCE: There are many neuroscience questions that can be answered by a high-resolution functional brain imaging system. Such a system would require the capability to visualize vasculature and measure neural activity by imaging the entire brain continually and in rapid succession in order to capture hemodynamic changes. Utilizing optical excitation and acoustic detection, photoacoustic technology enables label-free quantification of changes in endogenous chromophores, such as oxyhemoglobin, deoxyhemoglobin, and total hemoglobin...

SIGNIFICANCE: Two-photon optogenetics combines nonlinear excitation with noninvasive activation of neurons to enable the manipulation of neural circuits with a high degree of spatial precision. Combined with two-photon population calcium imaging, these approaches comprise a flexible platform for all-optical interrogation of neural circuits. However, a multitude of optical and biological factors dictate the exact precision of this approach in vivo , where it is most usefully applied. AIM: We aimed to assess how the optical point spread function (OPSF) contributes to the spatial precision of two-photon photostimulation in neurobiology...

The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood-brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer's disease. This review provides a comprehensive overview of tPBM...

SIGNIFICANCE: A fleeting flash aligned vertically with an object remaining stationary in the head-centered space would be perceived as lagging behind the object during the observer's horizontal head rotation. This perceptual mislocalization is an illusion named head-rotation-induced flash-lag effect (hFLE). While many studies have investigated the neural mechanism of the classical visual FLE, the hFLE has been hardly investigated. AIM: We measured the cortical activity corresponding to the hFLE on participants experiencing passive head rotations using functional near-infrared spectroscopy...

SIGNIFICANCE: The non-invasive measurement of cerebral blood flow based on diffuse optical techniques has seen increased interest as a research tool for cerebral perfusion monitoring in critical care and functional brain imaging. Diffuse correlation spectroscopy (DCS) and speckle contrast optical spectroscopy (SCOS) are two such techniques that measure complementary aspects of the fluctuating intensity signal, with DCS quantifying the temporal fluctuations of the signal and SCOS quantifying the spatial blurring of a speckle pattern...

SIGNIFICANCE: Diffuse correlation spectroscopy (DCS) is an optical method to measure relative changes in cerebral blood flow (rCBF) in the microvasculature. Each heartbeat generates a pulsatile signal with distinct morphological features that we hypothesized to be related to intracranial compliance (ICC). AIM: We aim to study how three features of the pulsatile rCBF waveforms: the augmentation index (AIx), the pulsatility index, and the area under the curve, change with respect to ICC...