Calcium Neuroimaging

SIGNIFICANCE: The initiation of goal-directed actions is a complex process involving the medial prefrontal cortex and dopaminergic inputs through the mesocortical pathway. However, it is unclear what information the mesocortical pathway conveys and how it impacts action initiation. In this study, we unveiled the indispensable role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions. AIM: To investigate the role of mesocortical axon terminals in encoding the execution of movements in self-initiated actions...

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences...

Large-scale imaging of brain activity with high spatio-temporal resolution is crucial for advancing our understanding of brain function. The existing neuroimaging techniques are largely limited by restricted field of view, slow imaging speed, or otherwise do not have the adequate spatial resolution to capture brain activities on a capillary and cellular level. To address these limitations, we introduce fluorescence localization microscopy aided with sparsely-labeled red blood cells for cortex-wide morphological and functional cerebral angiography with 4...

Although previous studies reported structural changes associated with electroconvulsive therapy (ECT) in major depressive disorder (MDD), the underlying molecular basis of ECT remains largely unknown. Here, we combined two independent structural MRI datasets of MDD patients receiving ECT and transcriptomic gene expression data from Allen Human Brain Atlas to reveal the molecular basis of ECT for MDD. We performed partial least square regression to explore whether/how gray matter volume (GMV) alterations were associated with gene expression level...

The abnormal aggregation of extracellular amyloid-<mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mi>β</mml:mi><mml:mspace/><mml:mo>(</mml:mo><mml:mi>A</mml:mi><mml:mi>β</mml:mi><mml:mo>)</mml:mo></mml:math> in senile plaques resulting in calcium <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mfenced><mml:mrow><mml:msup><mml:mrow><mml:mi>C</mml:mi><mml:mi>a</mml:mi></mml:mrow><mml:mrow><mml:mo>+</mml:mo><mml:mn>2</mml:mn></mml:mrow></mml:msup></mml:mrow></mml:mfenced></mml:math> dyshomeostasis is one of the primary symptoms of Alzheimer's disease (AD)...

Timely diagnosis of mild traumatic brain injury (mTBI) remains challenging due to the rapid recovery of acute symptoms and the absence of evidence of injury in static neuroimaging scans. Furthermore, while longitudinal tracking of mTBI is essential in understanding how the diseases progresses/regresses over time for enhancing personalized patient care, a standardized approach for this purpose is not yet available. Recent functional neuroimaging studies have provided evidence of brain function alterations following mTBI, suggesting mTBI-detection models can be built based on these changes...

SIGNIFICANCE: Advances in genetically encoded sensors and two-photon imaging have unlocked functional imaging at the level of single dendritic spines. Synaptic activity can be measured in real time in awake animals. However, tools are needed to facilitate the analysis of the large datasets acquired by the approach. Commonly available software suites for imaging calcium transients in cell bodies are ill-suited for spine imaging as dendritic spines have structural characteristics distinct from those of the cell bodies...

SIGNIFICANCE: Genetically encoded calcium ion (<mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mi>Ca</mml:mi><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math>) indicators (GECIs) are powerful tools for monitoring intracellular <mml:math xmlns:mml="https://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mi>Ca</mml:mi><mml:mrow><mml:mn>2</mml:mn><mml:mo>+</mml:mo></mml:mrow></mml:msup></mml:mrow></mml:math> concentration changes in living cells and model organisms...

SIGNIFICANCE: Optical imaging has accelerated neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters, and voltage are commonly used for optical recording of neuronal activity. However, fluorescence imaging is limited to superficial regions for in vivo activity imaging, due to photon scattering and absorbance. Bioluminescence imaging offers a promising alternative for achieving activity imaging in deeper brain regions without hardware implanted within the brain...

Susceptibility-weighted imaging (SWI) is a magnetic resonance imaging (MRI) technique able to depict the magnetic susceptibility produced by different substances, such as deoxyhemoglobin, calcium, and iron. The main application of SWI in clinical neuroimaging is detecting microbleedings and venous vasculature. Quantitative analyses of SWI have been developed over the last few years, aimed to offer new parameters, which could be used as neuroimaging biomarkers. Each technique has shown pros and cons, but no gold standard exists yet...

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: The function of the hippocampus in behavior and cognition has long been studied primarily through electrophysiological recordings from freely moving rodents. However, the application of optical recording methods, particularly multiphoton fluorescence microscopy, in the last decade or two has dramatically advanced our understanding of hippocampal function. This article provides a comprehensive overview of techniques and biological findings obtained from multiphoton imaging of hippocampal neural circuits...

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...

In recent decades, various subfields within neuroscience, spanning molecular, cellular, and systemic dimensions, have significantly advanced our understanding of the elaborate molecular and cellular mechanisms that underpin learning, memory, and adaptive behaviors. There have been notable advancements in imaging techniques, particularly in reaching superficial brain structures. This progress has led to their widespread adoption in numerous laboratories. However, essential physiological and cognitive processes, including sensory integration, emotional modulation of motivated behavior, motor regulation, learning, and memory consolidation, are intricately encoded within deeper brain structures...

In the field of neuroscience, the importance of constructing closed-loop experimental systems has increased in conjunction with technological advances in measuring and controlling neural activity in live animals. We provide an overview of recent technological advances in the field, focusing on closed-loop experimental systems where multiphoton microscopy-the only method capable of recording and controlling targeted population activity of neurons at a single-cell resolution in vivo -works through real-time feedback...

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...

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: 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...

Genetically encoded voltage indicators (GEVIs) are protein-based optical sensors that allow for measurements from genetically defined populations of neurons. Although in vivo imaging in the mammalian brain with early generation GEVIs was difficult due to poor membrane expression and low signal-to-noise ratio, newer and more sensitive GEVIs have begun to make them useful for answering fundamental questions in neuroscience. We discuss principles of imaging using GEVIs and genetically encoded calcium indicators, both useful tools for in vivo imaging of neuronal activity, and review some of the recent mechanistic advances that have led to GEVI improvements...

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...