scholarly journals Effective and Efficient Neural Networks for Spike Inference from In Vivo Calcium Imaging

2021 ◽  
Author(s):  
Zhanhong Zhou ◽  
Chung Tin

AbstractCalcium imaging technique provides irreplaceable advantages in monitoring large population of neuronal activities simultaneously. However, due to the generally low signal to noise ratio (SNR) of the calcium signal and variability in dye properties, it is still challenging to faithfully infer neuronal spikes from these calcium signals, especially from in vivo experiments. In this study, we tackled the problem of both spike-rate and spike-event predictions using a data-driven approach, based on a public pool of dataset with simultaneously recorded calcium and electrophysiological signals using different dyes and recorded from different brain regions. We proposed the ENS2 (effective and efficient neural networks for spike inference from calcium signals) system using raw calcium inputs and it consistently outperforms state-of-the-arts algorithms in both spike-rate and spike-event predictions with reduced computational load. We have also demonstrated that factors such as sampling rates, smoothing window sizes and parametric evaluation metrics could readily bias the interpretation of inference performance. We concluded that optimizing our system for spike-event prediction could produce a more versatile inference system for real neuroscience studies.

2021 ◽  
Author(s):  
Seongtak Kang ◽  
Jiho Park ◽  
Kyungsoo Kim ◽  
Sung-Ho Lim ◽  
Joon Ho Choi ◽  
...  

In vivo calcium imaging is a standard neuroimaging technique that allows the simultaneous observation of neuronal population activity. In calcium imaging, the activation signals of neurons are key information for the investigation of neural circuits. For efficient extraction of the calcium signals of neurons, selective detection of the region of interest (ROI) pixels corresponding to the active subcellular region of the target neuron is essential. However, current ROI detection methods for calcium imaging data exhibit relatively low extraction performance from neurons with a low signal-to-noise power ratio (SNR). This is problematic because a low SNR is unavoidable in many biological experimental settings. Therefore, we propose an iterative correlation-based ROI detection (ICoRD) method that robustly extracts the calcium signal of the target neuron from a calcium imaging series with severe noise. ICoRD extracts calcium signals closer to the ground truth than the conventional method from simulated calcium imaging data in all low SNR ranges. Additionally, this study confirmed that ICoRD robustly extracts activation signals against noise, even within in vivo environments. ICoRD showed reliable detection from neurons with low SNR and sparse activation, which were not detected by the conventional methods. ICoRD will facilitate our understanding of neural circuit activity by providing significantly improved ROI detection from noisy images.


2013 ◽  
Vol 110 (1) ◽  
pp. 243-256 ◽  
Author(s):  
Jakub Tomek ◽  
Ondrej Novak ◽  
Josef Syka

Two-Photon Processor (TPP) is a versatile, ready-to-use, and freely available software package in MATLAB to process data from in vivo two-photon calcium imaging. TPP includes routines to search for cell bodies in full-frame (Search for Neural Cells Accelerated; SeNeCA) and line-scan acquisition, routines for calcium signal calculations, filtering, spike-mining, and routines to construct parametric fields. Searching for somata in artificial in vivo data, our algorithm achieved better performance than human annotators. SeNeCA copes well with uneven background brightness and in-plane motion artifacts, the major problems in simple segmentation methods. In the fast mode, artificial in vivo images with a resolution of 256 × 256 pixels containing ∼100 neurons can be processed at a rate up to 175 frames per second (tested on Intel i7, 8 threads, magnetic hard disk drive). This speed of a segmentation algorithm could bring new possibilities into the field of in vivo optophysiology. With such a short latency (down to 5–6 ms on an ordinary personal computer) and using some contemporary optogenetic tools, it will allow experiments in which a control program can continuously evaluate the occurrence of a particular spatial pattern of activity (a possible correlate of memory or cognition) and subsequently inhibit/stimulate the entire area of the circuit or inhibit/stimulate a different part of the neuronal system. TPP will be freely available on our public web site. Similar all-in-one and freely available software has not yet been published.


2021 ◽  
Author(s):  
Alex A. Legaria ◽  
Julia A. Licholai ◽  
Alexxai V. Kravitz

AbstractFiber photometry recordings are commonly used as a proxy for neuronal activity, based on the assumption that increases in bulk calcium fluorescence reflect increases in spiking of the underlying neural population. However, this assumption has not been adequately tested. Here, using endoscopic calcium imaging in the striatum we report that the bulk fluorescence signal correlates weakly with somatic calcium signals, suggesting that this signal does not reflect spiking activity, but may instead reflect subthreshold changes in neuropil calcium. Consistent with this suggestion, the bulk fluorescence photometry signal correlated strongly with neuropil calcium signals extracted from these same endoscopic recordings. We further confirmed that photometry did not reflect striatal spiking activity with simultaneous in vivo extracellular electrophysiology and fiber photometry recordings in awake behaving mice. We conclude that the fiber photometry signal should not be considered a proxy for spiking activity in neural populations in the striatum.Significance statementFiber photometry is a technique for recording brain activity that has gained popularity in recent years due to it being an efficient and robust way to record the activity of genetically defined populations of neurons. However, it remains unclear what cellular events are reflected in the photometry signal. While it is often assumed that the photometry signal reflects changes in spiking of the underlying cell population, this has not been adequately tested. Here, we processed calcium imaging recordings to extract both somatic and non-somatic components of the imaging field, as well as a photometry signal from the whole field. Surprisingly, we found that the photometry signal correlated much more strongly with the non-somatic than the somatic signals. This suggests that the photometry signal most strongly reflects subthreshold changes in calcium, and not spiking. We confirmed this point with simultaneous fiber photometry and extracellular spiking recordings, again finding that photometry signals relate poorly to spiking in the striatum. Our results may change interpretations of studies that use fiber photometry as an index of spiking output of neural populations.


2020 ◽  
Vol 4 (s1) ◽  
pp. 11-11
Author(s):  
Tyler Nguyen ◽  
Zoe Vriesman ◽  
Peter Andrews ◽  
Sehban Masood ◽  
M Stewart ◽  
...  

OBJECTIVES/GOALS: Our goal is to develop a non-invasive stimulation technique using magneto-electric nanoparticles (MENs) for inducing and enhancing neuronal activity with high spatial and temporal resolutions and minimal toxicity, which can potentially be used as a more effective approach to brain stimulation. METHODS/STUDY POPULATION: MENs compose of core-shell structures that are attracted to strong external magnetic field (~5000 Gauss) but produces electric currents with weaker magnetic field (~450 Gauss). MENs were IV treated into mice and drawn to the brain cortex with a strong magnetic field. We then stimulate MENs with a weaker magnetic field via electro magnet. With two photon calcium imaging, we investigated both the temporal and spatial effects of MENs on neuronal activity both in vivo and in vitro. We performed mesoscopic whole brain calcium imaging on awake animal to assess the MENs effects. Furthermore, we investigated the temporal profile of MENs in the vasculatures post-treatment and its toxicities to CNS. RESULTS/ANTICIPATED RESULTS: MENs were successfully localized to target cortical regions within 30 minutes of magnetic application. After wirelessly applying ~450 G magnetic field between 10-20 Hz, we observed a dramatic increase of calcium signals (i.e. neuronal excitability) both in vitro cultured neurons and in vivo treated animals. Whole brain imaging of awake mice showed a focal increase in calcium signals at the area where MENs localized and the signals spread to regions further away. We also found MENs stimulatory effects lasted up to 24 hours post treatment. MEN stimulation increases c-Fos expression but resulted in no inflammatory changes, up to one week, by assessing microglial or astrocytes activations. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study shows, through controlling the applied magnetic field, MENs can be focally delivered to specific cortical regions with high efficacy and wirelessly activated neurons with high spatial and temporal resolution. This method shows promising potential to be a new non-invasive brain modulation approach disease studies and treatments.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mineki Oguchi ◽  
Jiang Jiasen ◽  
Toshihide W. Yoshioka ◽  
Yasuhiro R. Tanaka ◽  
Kenichi Inoue ◽  
...  

AbstractIn vivo calcium imaging with genetically encoded indicators has recently been applied to macaque brains to monitor neural activities from a large population of cells simultaneously. Microendoscopic calcium imaging combined with implantable gradient index lenses captures neural activities from deep brain areas with a compact and convenient setup; however, this has been limited to rodents and marmosets. Here, we developed miniature fluorescent microscopy to image neural activities from the primary visual cortex of behaving macaques. We found tens of clear fluorescent signals from three of the six brain hemispheres. A subset of these neurons showed clear retinotopy and orientation tuning. Moreover, we successfully decoded the stimulus orientation and tracked the cells across days. These results indicate that microendoscopic calcium imaging is feasible and reasonable for investigating neural circuits in the macaque brain by monitoring fluorescent signals from a large number of neurons.


2020 ◽  
Author(s):  
Alice M. Li ◽  
Robert A. Hill ◽  
Jaime Grutzendler

ABSTRACTNeocortical heterotopia consist of ectopic neuronal clusters that are frequently found in individuals with cognitive disability and epilepsy. However, their pathogenesis remains poorly understood due in part to a lack of tractable animal models. We have developed an inducible model of focal heterotopia that enables their precise spatiotemporal control and high-resolution optical imaging in live mice. Here we report that heterotopia are associated with striking patterns of hypermyelinated and circumferentially projecting axons around neuronal clusters. Despite their aberrant axonal patterns, in vivo calcium imaging revealed that heterotopic neurons remain functionally connected to other brain regions, highlighting their potential to influence global neural networks. These aberrant patterns only form when heterotopia are induced during a critical embryonic temporal window, but not in early postnatal development. Our model provides a new way to investigate heterotopia formation in vivo and revealed features suggesting the existence of developmentally-modulated, neuron-derived axon guidance and myelination factors.


2020 ◽  
Vol 32 (6) ◽  
pp. 1144-1167
Author(s):  
Mengyu Tu ◽  
Ruohe Zhao ◽  
Avital Adler ◽  
Wen-Biao Gan ◽  
Zhe S. Chen

Large-scale fluorescence calcium imaging methods have become widely adopted for studies of long-term hippocampal and cortical neuronal dynamics. Pyramidal neurons of the rodent hippocampus show spatial tuning in freely foraging or head-fixed navigation tasks. Development of efficient neural decoding methods for reconstructing the animal's position in real or virtual environments can provide a fast readout of spatial representations in closed-loop neuroscience experiments. Here, we develop an efficient strategy to extract features from fluorescence calcium imaging traces and further decode the animal's position. We validate our spike inference-free decoding methods in multiple in vivo calcium imaging recordings of the mouse hippocampus based on both supervised and unsupervised decoding analyses. We systematically investigate the decoding performance of our proposed methods with respect to the number of neurons, imaging frame rate, and signal-to-noise ratio. Our proposed supervised decoding analysis is ultrafast and robust, and thereby appealing for real-time position decoding applications based on calcium imaging.


2020 ◽  
Author(s):  
Kevin G. Johnston ◽  
Steven F. Grieco ◽  
Zhaoxia Yu ◽  
Suoqin Jin ◽  
Tong Shen ◽  
...  

SummaryIn vivo calcium imaging enables simultaneous recording of large neuronal ensembles while engaged in operations such as learning and memory. However, such in vivo optical recordings are typically subject to motion artifact and background contamination from neurons and blood vessels. Further, population cell tracking across multiple recordings is complicated by non-rigid transformation induced by cell movements and field shifts. We introduce the novel method SCOUT for Single-Cell SpatiOtemporal LongitUdinal Tracking, consisting of two crucial parts: (1) imposition of spatial constraints on neuronal footprints extracted from individual optical recordings to improve ROI selection and eliminate false discoveries, and (2) application of a predictor-corrector, using spatiotemporal correlation of extracted neurons across sessions, for population cell tracking across multiple sessions. SCOUT empirically outperforms current methods for cell extraction and tracking in long-term multi-session imaging experiments across multiple brain regions. Application of this method allows for robust longitudinal analysis of contextual discrimination associated neural ensemble dynamics in the hippocampus up to 60 days.


2018 ◽  
Author(s):  
Annet Glas ◽  
Mark Huebener ◽  
Tobias Bonhoeffer ◽  
Pieter M Goltstein

Miniaturized microscopes are lightweight imaging devices that allow optical recordings from neurons in freely moving animals over the course of weeks. Despite their ubiquitous use, individual neuronal responses measured with these microscopes have not been directly compared to those obtained with established in vivo imaging techniques such as bench-top two-photon microscopes. To achieve this, we performed calcium imaging in mouse primary visual cortex while presenting animals with drifting gratings. We identified the same neurons in image stacks acquired with both microscopy methods and quantified orientation tuning of individual neurons. The response amplitude and signal-to-noise ratio of calcium transients recorded upon visual stimulation were highly correlated between both microscopy methods, although influenced by neuropil contamination in miniaturized microscopy. Tuning properties, calculated for individual orientation tuned neurons, were strongly correlated between imaging techniques. Thus, neuronal tuning features measured with a miniaturized microscope are quantitatively similar to those obtained with a two-photon microscope.


2022 ◽  
Author(s):  
Yu-Long Huang ◽  
Yi-Ru Lin ◽  
Shang-Yueh Tsai

Abstract Quantification of metabolites concentrations in institutional unit (IU) for between subject and long-term comparison is considered important strategy in the applications of magnetic resonance spectroscopy (MRS). The aim of this study is to investigate if metabolite concentrations quantified by convolutional neuronal network (CNN) based method associated with a proposed scaling procedure can reflect variations of the metabolite concentrations in institution unit (IU) at different brain regions with different signal-to-noise-ratio (SNR) and linewidth (LW). An error index based on standard error (SE) is proposed to indicate the confidence levels on the prediction for metabolites. In vivo MRS spectra were collected at 3 brain regions from 44 subjects at 3T system. Metabolite concentrations in IU quantified by LCModel and CNN from 44 subjects were compared. For in vivo spectra characterized under different spectral quality in terms of SNR and LW, line narrowing and noise free spectra were successfully exported by CNN. Concentrations of five metabolites quantified by CNN and LCModel are in similar range with statistically significant Pearson’s correlation coefficients (0.28~0.70). SE of the metabolites show positive correlation with Cramer-Rao lower bound (CRLB) (r=0.60) and with absolute CRLB (r=0.84). In conclusion, the CNN based method with the proposed scaling procedures can be used to quantify in vivo MRS spectra. The concentrations of five major metabolites were reported in IU, which are in the same range as those quantified using a routine MRS quantification procedures by LCModel. The SE can be used as error index indicating predicted uncertainties for metabolites with the information similar to the absolute CRLB.


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