Orientation Tuning and End-stopping in Macaque V1 Studied with Two-photon Calcium Imaging

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.

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Critical-Period Visual Deprivation Disrupts Binocular Integration but Spares Spatial Acuity in the Geniculocortical Pathway

10.1101/484774 ◽

2018 ◽

Author(s):

Carey Y. L. Huh ◽

Karim Abdelaal ◽

Kirstie J. Salinas ◽

Diyue Gu ◽

Jack Zeitoun ◽

...

Keyword(s):

Critical Period ◽

Monocular Deprivation ◽

Orientation Tuning ◽

Visual Responses ◽

V1 Neurons ◽

Two Photon ◽

Spatial Acuity ◽

A Site

ABSTRACTMonocular deprivation (MD) during the juvenile critical period leads to long-lasting impairments in binocular function and visual acuity. The site of these changes has been widely considered to be cortical. However, recent evidence indicates that binocular integration may first occur in the dorsolateral geniculate nucleus of the thalamus (dLGN), raising the question of whether MD during the critical period may produce long-lasting deficits in dLGN binocular integration. Using in vivo two-photon Ca2+ imaging of dLGN afferents and excitatory neurons in superficial layers of primary visual cortex (V1), we demonstrate that critical-period MD leads to a persistent and selective loss of binocular dLGN inputs, while leaving spatial acuity in the thalamocortical pathway intact. Despite being few in number, binocular dLGN boutons display remarkably robust visual responses, on average twice stronger than monocular boutons, and their responses are exquisitely well-matched between the eyes. To our surprise, we found that MD leads to a profound binocular mismatch of response amplitude, spatial frequency and orientation tuning detected at the level of single thalamocortical synapses. In comparison, V1 neurons display deficits in both binocular integration and spatial acuity following MD. Our data provide the most compelling evidence to date demonstrating that following critical-period MD, binocular deficits observed at the level of V1 may at least in part originate from dLGN binocular dysfunction, while spatial acuity deficits arise from cortical circuits. These findings highlight a hitherto unknown role of the thalamus as a site for developmental refinement of binocular vision.

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

Journal of Neurophysiology ◽

10.1152/jn.00725.2011 ◽

2012 ◽

Vol 107 (3) ◽

pp. 923-936 ◽

Cited By ~ 17

Author(s):

Ian Nauhaus ◽

Kristina J. Nielsen ◽

Edward M. Callaway

Keyword(s):

Calcium Imaging ◽

Tuning Curve ◽

Receptive Fields ◽

Fundamental Property ◽

Calcium Transient ◽

Cell Types ◽

Operating Regime ◽

Orientation Tuning ◽

Two Photon ◽

Contrast Invariance

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.

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Macaque V1 responses to 2nd-order contrast-modulated stimuli and the possible subcortical and cortical contributions

10.1101/2021.01.28.428627 ◽

2021 ◽

Author(s):

Nian-Sheng Ju ◽

Shu-Chen Guan ◽

Shi-Ming Tang ◽

Cong Yu

Keyword(s):

Calcium Imaging ◽

Linear Filters ◽

V1 Neurons ◽

Two Photon ◽

Second Stage ◽

Stimulus Representation ◽

Lm Adaptation

AbstractV1 neurons as linear filters supposedly only respond to 1st-order luminance-modulated (LM) stimuli, but not 2nd-order contrast-modulated (CM) ones. To solve this difficulty, filter-rectify-filter models are proposed, in which first-stage filters respond to CM stimulus elements, and the nonlinear-rectified outputs are summed by a second-stage filter for CM stimulus representation. Correspondingly, neurophysiological evidence shows V1/A17 neurons less responsive to CM stimuli than V2/A18 neurons. Here we used two-photon calcium imaging to demonstrate substantial V1 responses to CM gratings with unimodally distributed LM/CM preferences. Moreover, LM responses are suppressed by LM and CM adaptations regardless of orientation, but CM responses are more suppressed by same-orientation LM and CM adaptations than by orthogonal ones. While LM adaptation results agree with the Hubel-Wiesel view of LGN contributions to V1 orientation responses, CM adaptation results, which include both orientation-unspecific and specific components, may suggest similar subcortical contributions plus additional refinement by recurrent intracortical interactions.

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Deficits in higher visual area representations in a mouse model of Angelman syndrome

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-020-09329-y ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Leah B. Townsend ◽

Kelly A. Jones ◽

Christopher R. Dorsett ◽

Benjamin D. Philpot ◽

Spencer L. Smith

Keyword(s):

Visual Cortex ◽

Mouse Model ◽

Primary Visual Cortex ◽

Angelman Syndrome ◽

Calcium Imaging ◽

Neurodevelopmental Disorders ◽

Synaptic Function ◽

Strong Response ◽

Intrinsic Signal ◽

Two Photon

Abstract Background Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). Methods Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. Results We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. Conclusion Assaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. Trial registration Not applicable.

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Curvature-processing domains in primate V4

eLife ◽

10.7554/elife.57502 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Rendong Tang ◽

Qianling Song ◽

Ying Li ◽

Rui Zhang ◽

Xingya Cai ◽

...

Keyword(s):

Calcium Imaging ◽

Visual Object ◽

Visual Object Recognition ◽

Intrinsic Signal ◽

Two Photon ◽

Contour Shape ◽

Wide Range ◽

Shape Tuning ◽

Common Shape

Neurons in primate V4 exhibit various types of selectivity for contour shapes, including curves, angles, and simple shapes. How are these neurons organized in V4 remains unclear. Using intrinsic signal optical imaging and two-photon calcium imaging, we observed submillimeter functional domains in V4 that contained neurons preferring curved contours over rectilinear ones. These curvature domains had similar sizes and response amplitudes as orientation domains but tended to separate from these regions. Within the curvature domains, neurons that preferred circles or curve orientations clustered further into finer scale subdomains. Nevertheless, individual neurons also had a wide range of contour selectivity, and neighboring neurons exhibited a substantial diversity in shape tuning besides their common shape preferences. In strong contrast to V4, V1 and V2 did not have such contour-shape-related domains. These findings highlight the importance and complexity of curvature processing in visual object recognition and the key functional role of V4 in this process.

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Color and orientation are jointly coded and spatially organized in primate primary visual cortex

Science ◽

10.1126/science.aaw5868 ◽

2019 ◽

Vol 364 (6447) ◽

pp. 1275-1279 ◽

Cited By ~ 28

Author(s):

Anupam K. Garg ◽

Peichao Li ◽

Mohammad S. Rashid ◽

Edward M. Callaway

Keyword(s):

Visual Cortex ◽

Single Cell ◽

Primary Visual Cortex ◽

Visual Stimulus ◽

Calcium Imaging ◽

Stimulus Space ◽

Single Neurons ◽

V1 Neurons ◽

Two Photon ◽

Rigorous Testing

Previous studies support the textbook model that shape and color are extracted by distinct neurons in primate primary visual cortex (V1). However, rigorous testing of this model requires sampling a larger stimulus space than previously possible. We used stable GCaMP6f expression and two-photon calcium imaging to probe a very large spatial and chromatic visual stimulus space and map functional microarchitecture of thousands of neurons with single-cell resolution. Notable proportions of V1 neurons strongly preferred equiluminant color over achromatic stimuli and were also orientation selective, indicating that orientation and color in V1 are mutually processed by overlapping circuits. Single neurons could precisely and unambiguously code for both color and orientation. Further analyses revealed systematic spatial relationships between color tuning, orientation selectivity, and cytochrome oxidase histology.

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Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex

PLoS ONE ◽

10.1371/journal.pone.0214954 ◽

2019 ◽

Vol 14 (4) ◽

pp. e0214954 ◽

Cited By ~ 6

Author(s):

Annet Glas ◽

Mark Hübener ◽

Tobias Bonhoeffer ◽

Pieter M. Goltstein

Keyword(s):

Visual Cortex ◽

Single Cell ◽

Calcium Imaging ◽

Orientation Tuning ◽

Cell Orientation ◽

Two Photon ◽

Mouse Visual Cortex

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Benchmarking miniaturized microscopy against two-photon calcium imaging using single-cell orientation tuning in mouse visual cortex

10.1101/494641 ◽

2018 ◽

Cited By ~ 1

Author(s):

Annet Glas ◽

Mark Huebener ◽

Tobias Bonhoeffer ◽

Pieter M Goltstein

Keyword(s):

Visual Cortex ◽

Calcium Imaging ◽

Visual Stimulation ◽

Signal To Noise Ratio ◽

Imaging Techniques ◽

Orientation Tuning ◽

Cell Orientation ◽

Two Photon ◽

Highly Correlated

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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