scholarly journals Fiber photometry does not reflect spiking activity in the striatum

2021 ◽  
Author(s):  
Alex A. Legaria ◽  
Julia A. Licholai ◽  
Alexxai V. Kravitz
Keyword(s):  
Neuronal Activity ◽  
Calcium Imaging ◽  
Brain Activity ◽  
Neural Population ◽  
Fluorescence Signal ◽  
Calcium Signals ◽  
Cellular Events ◽  
Neural Populations ◽  
Spiking Activity

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.

scholarly journals 4009 Magneto-electric nanoparticles (MENs) cobalt ferrite-barrium titanate (CoFe2O4–BaTiO3) for non-invasive neuromodulation

2020 ◽  
Vol 4 (s1) ◽  
pp. 11-11
Author(s):  
Tyler Nguyen ◽  
Zoe Vriesman ◽  
Peter Andrews ◽  
Sehban Masood ◽  
M Stewart ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Post Treatment ◽  
Calcium Signals ◽  
Whole Brain ◽  
Non Invasive ◽  
Cortical Regions

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.

In Vivo Three-photon Calcium Imaging of Brain Activity from Layer 6 Neurons in Mouse Brain

2014 ◽  
Author(s):  
Dimitre G. Ouzounov ◽  
Nicholas Horton ◽  
Tianyu Wang ◽  
Danielle Feng ◽  
Nozomi Nishimura ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Calcium Imaging ◽  
Brain Activity

scholarly journals In vivo direct imaging of neuronal activity at high temporo-spatial resolution

2021 ◽  
Author(s):  
Phan Tan Toi ◽  
Hyun Jae Jang ◽  
Kyeongseon Min ◽  
Sung-Phil Kim ◽  
Seung-Kyun Lee ◽  
...  
Keyword(s):  
Spatial Resolution ◽  
Neuronal Activity ◽  
Functional Organization ◽  
Direct Imaging ◽  
Whisker Pad ◽  
Novel Method ◽  
Mice Brain ◽  
Noninvasive Neuroimaging ◽  
Spiking Activity

There has been a longstanding demand for noninvasive neuroimaging methods capable of detecting neuronal activity at both high temporal and spatial resolution. Here, we propose a novel method that enables Direct Imaging of Neuronal Activity for functional MRI (termed DIANA-fMRI) that can dynamically image spiking activity in milliseconds precision, while retaining the original benefit of high spatial resolution of MRI. DIANA-fMRI was demonstrated through in vivo mice brain imaging at 9.4 T applying electrical whisker-pad stimulation, directly imaging the spiking activity as well as capturing its sequential propagation along the thalamocortical pathway, as further confirmed through in vivo spike recording and optogenetics. DIANA-fMRI will open up new avenues in brain science by providing a deeper understanding of the brain's functional organization including neural networks.

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

2021 ◽  
Author(s):  
Zhanhong Zhou ◽  
Chung Tin
Keyword(s):  
Calcium Imaging ◽  
Signal To Noise Ratio ◽  
Large Population ◽  
Brain Regions ◽  
Spike Rate ◽  
Calcium Signal ◽  
Calcium Signals ◽  
Inference System ◽  
Spike Event

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.

scholarly journals Robustness of spike deconvolution for calcium imaging of neural spiking

2017 ◽  
Author(s):  
Marius Pachitariu ◽  
Carsen Stringer ◽  
Kenneth D. Harris
Keyword(s):  
Neural Networks ◽  
Calcium Imaging ◽  
Ground Truth ◽  
The Other ◽  
Powerful Method ◽  
Challenging Problem ◽  
Calcium Signals ◽  
Multiple Datasets ◽  
Neural Spiking ◽  
Neural Populations

AbstractCalcium imaging is a powerful method to record the activity of neural populations, but inferring spike times from calcium signals is a challenging problem. We compared multiple approaches using multiple datasets with ground truth electrophysiology, and found that simple non-negative deconvolution (NND) outperformed all other algorithms. We introduce a novel benchmark applicable to recordings without electrophysiological ground truth, based on the correlation of responses to two stimulus repeats, and used this to show that unconstrained NND also outperformed the other algorithms when run on “zoomed out” datasets of ~10,000 cell recordings. Finally, we show that NND-based methods match the performance of a supervised method based on convolutional neural networks, while avoiding some of the biases of such methods, and at much faster running times. We therefore recommend that spikes be inferred from calcium traces using simple NND, due to its simplicity, efficiency and accuracy.

scholarly journals Online analysis of microendoscopic 1-photon calcium imaging data streams

2021 ◽  
Vol 17 (1) ◽  
pp. e1008565
Author(s):  
Johannes Friedrich ◽  
Andrea Giovannucci ◽  
Eftychios A. Pnevmatikakis
Keyword(s):  
Neuronal Activity ◽  
Calcium Imaging ◽  
Computing Time ◽  
Video Data ◽  
Streaming Data ◽  
Live Streaming ◽  
Imaging Data ◽  
Online Analysis ◽  
Real Time Processing

In vivo calcium imaging through microendoscopic lenses enables imaging of neuronal populations deep within the brains of freely moving animals. Previously, a constrained matrix factorization approach (CNMF-E) has been suggested to extract single-neuronal activity from microendoscopic data. However, this approach relies on offline batch processing of the entire video data and is demanding both in terms of computing and memory requirements. These drawbacks prevent its applicability to the analysis of large datasets and closed-loop experimental settings. Here we address both issues by introducing two different online algorithms for extracting neuronal activity from streaming microendoscopic data. Our first algorithm, OnACID-E, presents an online adaptation of the CNMF-E algorithm, which dramatically reduces its memory and computation requirements. Our second algorithm proposes a convolution-based background model for microendoscopic data that enables even faster (real time) processing. Our approach is modular and can be combined with existing online motion artifact correction and activity deconvolution methods to provide a highly scalable pipeline for microendoscopic data analysis. We apply our algorithms on four previously published typical experimental datasets and show that they yield similar high-quality results as the popular offline approach, but outperform it with regard to computing time and memory requirements. They can be used instead of CNMF-E to process pre-recorded data with boosted speeds and dramatically reduced memory requirements. Further, they newly enable online analysis of live-streaming data even on a laptop.

scholarly journals Direct Evaluation of L-DOPA Actions on Neuronal Activity of Parkinsonian TissueIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Víctor Plata ◽  
Mariana Duhne ◽  
Jesús E. Pérez-Ortega ◽  
Janet Barroso-Flores ◽  
Elvira Galarraga ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Neuronal Excitability ◽  
Imaging Techniques ◽  
Direct Evaluation ◽  
Disease Evolution

Physiological and biochemical experimentsin vivoandin vitrohave explored striatal receptor signaling and neuronal excitability to posit pathophysiological models of Parkinson's disease. However, when therapeutic approaches, such as dopamine agonists, need to be evaluated, behavioral tests using animal models of Parkinson's disease are employed. To our knowledge, recordings of population neuronal activityin vitroto assess anti-Parkinsonian drugs and the correlation of circuit dynamics with disease state have only recently been attempted. We have shown that Parkinsonian pathological activity of neuronal striatal circuits can be characterized inin vitrocerebral tissue. Here, we show that calcium imaging techniques, capable of recording dozens of neurons simultaneously with single-cell resolution, can be extended to assess the action of therapeutic drugs. We used L-DOPA as a prototypical anti-Parkinsonian drug to show the efficiency of this proposed bioassay. In a rodent model of early Parkinson's disease, Parkinsonian neuronal activity can be returned to control levels by the bath addition of L-DOPA in a reversible way. This result raises the possibility to use calcium imaging techniques to measure, quantitatively, the actions of anti-Parkinsonian drugs over time and to obtain correlations with disease evolution and behavior.

scholarly journals The relationship between voltage-sensitive dye imaging signals and spiking activity of neural populations in primate V1

2012 ◽  
Vol 107 (12) ◽  
pp. 3281-3295 ◽  
Author(s):  
Yuzhi Chen ◽  
Chris R. Palmer ◽  
Eyal Seidemann
Keyword(s):  
Neural Population ◽  
Orientation Tuning ◽  
Visual Responses ◽  
Voltage Sensitive Dye ◽  
Population Responses ◽  
Neural Populations ◽  
The Relationship ◽  
Integration Area ◽  
Spiking Activity ◽  
Voltage Sensitive Dye Imaging

Voltage-sensitive dye imaging (VSDI) is a powerful technique for measuring neural population responses from a large cortical region simultaneously with millisecond temporal resolution and columnar spatial resolution. However, the relationship between the average VSDI signal and the average spiking activity of neural populations is largely unknown. To better understand this relationship, we compared visual responses measured from V1 of behaving monkeys using VSDI and single-unit electrophysiology. We found large and systematic differences between position and orientation tuning properties obtained with these two techniques. We then determined that a simple computational model could explain these tuning differences. This model, together with our experimental results, allowed us to estimate the quantitative relationship between the average VSDI signal and local spiking activity. We found that this relationship is similar to the previously reported nonlinear relationship between average membrane potential and spike rate in single V1 neurons, suggesting that VSDI signals are dominated by subthreshold synaptic activity. This model, together with the VSDI measured maps for spatial position (retinotopy) and orientation, also allowed us to estimate the spatial integration area over which neural responses contribute to the VSDI signal at a given location. We found that the VSDI-integration area is consistent with a Gaussian envelope with a space constant of ∼230 μm. Finally, we show how this model and estimated parameters can be used to predict the pattern of population responses at the level of spiking activity from VSDI responses.

scholarly journals Long-term dynamics of aberrant neuronal activity in Alzheimer’s disease

2019 ◽  
Author(s):  
V. Korzhova ◽  
P. Marinković ◽  
P. M. Goltstein ◽  
J. Herms ◽  
S. Liebscher
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Amyloid Plaque ◽  
Activity Levels ◽  
Highly Active ◽  
Over Time

SummaryAlzheimer’s disease (AD) is associated with aberrant neuronal activity levels. How those activity alterations emerge and how stable they are over time in vivo, however, remains elusive to date. To address these questions we chronically recorded the activity from identified neurons in cortex of awake APPPS1 transgenic mice and their non-transgenic littermates over the course of 4 weeks by means of calcium imaging. Surprisingly, aberrant neuronal activity was very stable over time. Moreover, we identified a slow progressive gain of activity of former intermediately active neurons as the main source of new highly active neurons. Interestingly, fluctuations in neuronal activity were independent from amyloid plaque proximity, but aberrant activity levels were more likely to persist close to plaques. These results support the notion that neuronal network pathology observed in AD patients is the consequence of stable single cell aberrant neuronal activity, a finding of potential therapeutic relevance.

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