scholarly journals Nonlinearity of two-photon Ca2+ imaging yields distorted measurements of tuning for V1 neuronal populations

2012 ◽  
Vol 107 (3) ◽  
pp. 923-936 ◽  
Author(s):  
Ian Nauhaus ◽  
Kristina J. Nielsen ◽  
Edward M. Callaway

We studied the relative accuracy of drifting gratings and noise stimuli for functionally characterizing neural populations using two-photon calcium imaging. Calcium imaging has the potential to distort measurements due to nonlinearity in the conversion from spikes to observed fluorescence. We demonstrate a dramatic impact of fluorescence saturation on functional measurements in ferret V1 by showing that responses to drifting gratings strongly violate contrast invariance of orientation tuning, a fundamental property of the spike rates. The observed relationship is consistent with saturation that clips the high-contrast tuning curve peaks by ∼40%. The nonlinearity was also apparent in mouse V1 responses to drifting gratings, but not as strong as in the ferret. Contrast invariance holds, however, for tuning curves measured with a randomized grating stimulus. This finding is consistent with prior work showing that the linear portion of a linear-nonlinear system can be recovered with reverse correlation. Furthermore, we demonstrate that a noise stimulus is more effective at keeping spike rates in the linear operating regime of a saturating nonlinearity, which both maximizes signal-to-noise ratios and simplifies the recovery of fast spike dynamics from slow calcium transients. Finally, we uncover spatiotemporal receptive fields by removing the nonlinearity and slow calcium transient from a model of fluorescence generation, which allowed us to observe dynamic sharpening of orientation tuning. We conclude that for two-photon recordings it is imperative that one considers the nonlinear distortion when designing stimuli and interpreting results, especially in sensory areas, species, or cell types with high firing rates.

2018 ◽  
Author(s):  
Thomas Deneux ◽  
Alexandre Kempf ◽  
Brice Bathellier

AbstractDetecting rapid coincident changes across sensory modalities is essential to recognize sudden threats and events. Using two-photon calcium imaging in identified cell types in awake mice, we show that auditory cortex (AC) neurons projecting to primary visual cortex (V1) preferentially encode the abrupt onsets of sounds. In V1, a sub-population of layer 1 interneurons gates this selective cross-modal information by a suppression specific to the absence of visual inputs. However, when large auditory onsets coincide with visual stimuli, visual responses are strongly boosted in V1. Thus, a dynamic asymmetric circuit across AC and V1 specifically identifies visual events starting simultaneously to sudden sounds, potentially catalyzing localization of new sound sources in the visual field.


2015 ◽  
Author(s):  
Stephanie Reynolds ◽  
Caroline S Copeland ◽  
Simon R Schultz ◽  
Pier Luigi Dragotti

Two-photon calcium imaging of the brain allows the spatiotemporal activity of neuronal networks to be monitored at cellular resolution. In order to analyse this activity it must first be possible to detect, with high temporal resolution, spikes from the time series corresponding to single neurons. Previous work has shown that finite rate of innovation (FRI) theory can be used to reconstruct spike trains from noisy calcium imaging data. In this paper we extend the FRI framework for spike detection from calcium imaging data to encompass data generated by a larger class of calcium indicators, including the genetically encoded indicator GCaMP6s. Furthermore, we implement least squares model-order estimation and perform a noise reduction procedure ('pre-whitening') in order to increase the robustness of the algorithm. We demonstrate high spike detection performance on real data generated by GCaMP6s, detecting 90% of electrophysiologically-validated spikes.


2009 ◽  
Vol 65 ◽  
pp. S172
Author(s):  
Yoshiya Mori ◽  
Koji Ikezoe ◽  
Junichi Furutaka ◽  
Kazuo Kitamura ◽  
Hiroshi Tamura ◽  
...  

2001 ◽  
Vol 85 (5) ◽  
pp. 2130-2149 ◽  
Author(s):  
Andrew Kayser ◽  
Nicholas J. Priebe ◽  
Kenneth D. Miller

We study a recently proposed “correlation-based,” push-pull model of the circuitry of layer 4 of cat visual cortex. This model was previously shown to explain the contrast-invariance of cortical orientation tuning. Here we show that it can simultaneously account for several contrast-dependent (c-d) “nonlinearities” in cortical responses. These include an advance with increasing contrast in the temporal phase of response to a sinusoidally modulated stimulus; a change in shape of the temporal frequency tuning curve, so that higher temporal frequencies may give little or no response at low contrast but reasonable responses at high contrast; and contrast saturation that occurs at lower contrasts in cortex than in the lateral geniculate nucleus (LGN). In the context of the model circuit, these properties arise from a mixture of nonlinear cellular and synaptic mechanisms: short-term synaptic depression, spike-rate adaptation, contrast-induced changes in cellular conductance, and the nonzero spike threshold. The former three mechanisms are sufficient to explain the experimentally observed increase in c-d phase advance in cortex relative to LGN. The c-d changes in temporal frequency tuning arise as a threshold effect: voltage modulations in response to higher-frequency inputs are only slightly above threshold at lower contrast, but become robustly suprathreshold at higher contrast. The other three nonlinear mechanisms also play a crucial role in this result, allowing contrast dependence of temporal frequency tuning to coexist with contrast-invariance of orientation tuning. Contrast saturation, and the observation that responses to stimuli of increasing temporal frequency saturate at increasingly high contrasts, can be induced both by the model's push-pull inhibition and by synaptic depression. Previous proposals explained these nonlinear response properties by assuming contrast-invariant orientation tuning as a starting point, and adding normalization by shunting inhibition derived equally from cells of all preferred orientations. The present proposal simultaneously explains both contrast-invariant orientation tuning and these contrast-dependent nonlinearities and requires only processing that is local in orientation, in agreement with intracellular measurements.


2020 ◽  
Author(s):  
Agostina Palmigiano ◽  
Francesco Fumarola ◽  
Daniel P. Mossing ◽  
Nataliya Kraynyukova ◽  
Hillel Adesnik ◽  
...  

AbstractIdentifying the regime in which the cortical microcircuit operates is a prerequisite to determine the mechanisms that mediate its response to stimulus. Classic modeling work has started to characterize this regime through the study of perturbations, but an encompassing perspective that links the full ensemble of the network’s response to appropriate descriptors of the cortical operating regime is still lacking. Here we develop a class of mathematically tractable models that exactly describe the modulation of the distribution of cell-type-specific calcium-imaging activity with the contrast of a visual stimulus. The model’s fit recovers signatures of the connectivity structure found in mouse visual cortex. Analysis of this structure subsequently reveal parameter-independent relations between the responses of different cell types to perturbations and each interneuron’s role in circuit-stabilization. Leveraging recent theoretical approaches, we derive explicit expressions for the distribution of responses to partial perturbations which reveal a novel, counter-intuitive effect in the sign of response functions.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Quentin Gaucher ◽  
Mariangela Panniello ◽  
Aleksandar Z Ivanov ◽  
Johannes C Dahmen ◽  
Andrew J King ◽  
...  

Primary cortical areas contain maps of sensory features, including sound frequency in primary auditory cortex (A1). Two-photon calcium imaging in mice has confirmed the presence of these global tonotopic maps, while uncovering an unexpected local variability in the stimulus preferences of individual neurons in A1 and other primary regions. Here we show that local heterogeneity of frequency preferences is not unique to rodents. Using two-photon calcium imaging in layers 2/3, we found that local variance in frequency preferences is equivalent in ferrets and mice. Neurons with multipeaked frequency tuning are less spatially organized than those tuned to a single frequency in both species. Furthermore, we show that microelectrode recordings may describe a smoother tonotopic arrangement due to a sampling bias towards neurons with simple frequency tuning. These results help explain previous inconsistencies in cortical topography across species and recording techniques.


2020 ◽  
Author(s):  
Nian-Sheng Ju ◽  
Shu-Chen Guan ◽  
Louis Tao ◽  
Shi-Ming Tang ◽  
Cong Yu

Abstract Orientation tuning is a fundamental response property of V1 neurons and has been extensively studied with single-/multiunit recording and intrinsic signal optical imaging. Long-term 2-photon calcium imaging allows simultaneous recording of hundreds of neurons at single neuron resolution over an extended time in awake macaques, which may help elucidate V1 orientation tuning properties in greater detail. We used this new technology to study the microstructures of orientation functional maps, as well as population tuning properties, in V1 superficial layers of 5 awake macaques. Cellular orientation maps displayed horizontal and vertical clustering of neurons according to orientation preferences, but not tuning bandwidths, as well as less frequent pinwheels than previous estimates. The orientation tuning bandwidths were narrower than previous layer-specific single-unit estimates, suggesting more precise orientation selectivity. Moreover, neurons tuned to cardinal and oblique orientations did not differ in quantities and bandwidths, likely indicating minimal V1 representation of the oblique effect. Our experimental design also permitted rough estimates of length tuning. The results revealed significantly more end-stopped cells at a more superficial 150 μm depth (vs. 300 μm), but unchanged orientation tuning bandwidth with different length tuning. These results will help construct more precise models of V1 orientation processing.


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.


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