FiPhA: an open-source platform for fiber photometry analysis.

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. Approach: FiPhA was developed using the R Shiny framework and offers interactive visualization, quality control, and batch processing functionalities in a user-friendly interface. Results: This application simplifies and streamlines the analysis process, thereby reducing labor and time requirements. It offers interactive visualizations, event-triggered average processing, powerful tools for filtering behavioral events, and quality control features. Conclusions: FiPhA is a valuable tool for behavioral neuroscientists working with discrete, event-based FP data. It addresses the challenges associated with analyzing and investigating such data, offering a robust and user-friendly solution without the complexity of having to hand-design custom analysis pipelines. This application thus helps standardize an approach to FP analysis.

Partial or Complete Loss of Norepinephrine Differentially Alters Contextual Fear and Catecholamine Release Dynamics in Hippocampal CA1.

Background: Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Methods: We generated 2 new mouse models of altered locus coeruleus-norepinephrine (NE) synthesis and utilized them together with GRABNE and GRABDA sensors and in vivo fiber photometry to investigate NE and dopamine (DA) release dynamics in the dorsal hippocampal CA1 during contextual fear conditioning. Results: Aversive foot shock increased both NE and DA release in the dorsal CA1, while freezing behavior associated with recall of fear memory was accompanied by decreased release. Moreover, we found that freezing at the recent time point was sensitive to both partial and complete loss of locus coeruleus-NE synthesis throughout prenatal and postnatal development, similar to previous observations of mice with global loss of NE synthesis beginning postnatally. In contrast, freezing at the remote time point was compromised only by complete loss of locus coeruleus-NE synthesis beginning prenatally. Conclusions: Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior and highlight complex relationships between genotype, sex, and NE signaling.

FiPhA: An Open-Source Platform for Fiber Photometry Analysis.

Significance: Fiber photometry 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 FiPhA (Fiber Photometry Analysis) app, which is a general-purpose fiber photometry 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. Approach: FiPhA was developed using the R Shiny framework and offers interactive visualization, quality control, and batch processing functionalities in a user-friendly interface. Results: This application simplifies and streamlines the analysis process, thereby reducing labor and time requirements. It offers interactive visualizations, event-triggered average processing, powerful tools for filtering behavioral events and quality control features. Conclusions: FiPhA is a valuable tool for behavioral neuroscientists working with discrete, event-based fiber photometry data. It addresses the challenges associated with analyzing and investigating such data, offering a robust and user-friendly solution without the complexity of having to hand-design custom analysis pipelines. This application thus helps standardize an approach to fiber photometry analysis.

The Chi-Square Test of Distance Correlation.

Distance correlation has gained much recent attention in the data science community: the sample statistic is straightforward to compute and asymptotically equals zero if and only if independence, making it an ideal choice to discover any type of dependency structure given sufficient sample size. One major bottleneck is the testing process: because the null distribution of distance correlation depends on the underlying random variables and metric choice, it typically requires a permutation test to estimate the null and compute the p-value, which is very costly for large amount of data. To overcome the difficulty, in this paper we propose a chi-square test for distance correlation. Method-wise, the chi-square test is non-parametric, extremely fast, and applicable to bias-corrected distance correlation using any strong negative type metric or characteristic kernel. The test exhibits a similar testing power as the standard permutation test, and can be utilized for K-sample and partial testing. Theory-wise, we show that the underlying chi-square distribution well approximates and dominates the limiting null distribution in upper tail, prove the chi-square test can be valid and universally consistent for testing independence, and establish a testing power inequality with respect to the permutation test.

Selective and Mechanically Robust Sensors for Electrochemical Measurements of Real-Time Hydrogen Peroxide Dynamics in Vivo.

Hydrogen peroxide (H2O2) is an endogenous molecule that plays several important roles in brain function: it is generated in cellular respiration, serves as a modulator of dopaminergic signaling, and its presence can indicate the upstream production of more aggressive reactive oxygen species (ROS). H2O2 has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD), creating a critical need to identify mechanisms by which H2O2 modulates cellular processes in general and how it affects the dopaminergic nigrostriatal pathway, in particular. Furthermore, there is broad interest in selective electrochemical quantification of H2O2, because it is often enzymatically generated at biosensors as a reporter for the presence of nonelectroactive target molecules. H2O2 fluctuations can be monitored in real time using fast-scan cyclic voltammetry (FSCV) coupled with carbon-fiber microelectrodes. However, selective identification is a critical issue when working in the presence of other molecules that generate similar voltammograms, such as adenosine and histamine. We have addressed this problem by fabricating a robust, H2O2-selective electrode. 1,3-Phenylenediamine (mPD) was electrodeposited on a carbon-fiber microelectrode to create a size-exclusion membrane, rendering the electrode sensitive to H2O2 fluctuations and pH shifts but not to other commonly studied neurochemicals. The electrodes are described and characterized herein. The data demonstrate that this technology can be used to ensure the selective detection of H2O2, enabling confident characterization of the role this molecule plays in normal physiological function as well as in the progression of PD and other neuropathies involving oxidative stress.

Salvage of proximal tibia fracture treated with locked compression plate.

The treatment of displaced proximal tibial fractures is challenging. Recent developments in the techniques of internal fixation, including the development of locking plates and minimally invasive surgical techniques have revolutionaries the treatment of such fractures. We present a case of proximal displaced tibial fracture that was treated with anatomical proximal tibial locking plate using minimally invasive percutaneous plate osteosynthesis. Patient made uneventful recovery even after he sustained re-injury and plate bending and was manipulated under anaesthesia for the same.