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Article ; Online: Stimulus-Driven Retinal Intrinsic Signal Optical Imaging in Mouse Demonstrates a Dominant Rod-Driven Component.

Begum, Momotaz / Joiner, Dorothy P / Ts'o, Daniel Y

Investigative ophthalmology & visual science

2020 Volume 61, Issue 8, Page(s) 37

Abstract: Purpose: The primary hypotheses tested are that (1) there exist stimulus-driven intrinsic optical signals in the mouse retina similar to those previously observed in other species, and (2) these optical signals require an intact rod photoreceptor ... ...

Abstract	Purpose: The primary hypotheses tested are that (1) there exist stimulus-driven intrinsic optical signals in the mouse retina similar to those previously observed in other species, and (2) these optical signals require an intact rod photoreceptor phototransduction cascade. Methods: We used 38 wild-type C57BL6J mice and 18 genetic knockout Gnat1-/- mice to study the light-evoked retinal intrinsic response. A custom mouse fundus camera delivered visual stimuli and collected mouse retinal imaging data of changes in retinal reflectance for further analysis. The retina was stimulated in the high-mesopic range with a 505-nm light-emitting diode while also being illuminated with 780-nm near-infrared light. Results: Wild-type C57BL6J mice yielded retinal imaging signals that typically showed a stimulus-driven decrease in retinal reflectance of ∼0.1%, with a time course of several seconds. The signals exhibit spatial specificity in the retina. Overall, the mouse imaging signals are similar in sign and time course to those reported in other mammalian species but are of lower amplitude. In contrast, functional retinal imaging of Gnat1-/- mice that lack a functional rod transducin yielded no such stimulus-driven signals. Conclusions: Previous studies have not shown which pathway component is essential for the generation of these imaged signals. The absence of the intrinsic signal responses in Gnat1-/- knockout mice indicates that a functional rod transducin is likely to be necessary for generating the retinal intrinsic signals. These studies, to the best of our knowledge, demonstrate for the first time in vivo mouse retinal functional imaging signals similar to those previously shown in other mammalian species.
MeSH term(s)	Animals ; Evoked Potentials, Visual ; Light Signal Transduction/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Optical Imaging/methods ; Photic Stimulation/instrumentation ; Photic Stimulation/methods ; Retina/physiopathology ; Retinal Rod Photoreceptor Cells/physiology ; Transducin/genetics ; Vision, Ocular/physiology
Chemical Substances	Gnat1 protein, mouse ; Transducin (EC 3.6.5.1)
Language	English
Publishing date	2020-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.61.8.37
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Article: Integration of color, orientation, and size functional domains in the ventral pathway.

Ghose, Geoffrey M / Ts'o, Daniel Y

Neurophotonics

2017 Volume 4, Issue 3, Page(s) 31216

Abstract: Functional specialization within the extrastriate areas of the ventral pathway associated with visual form analysis is poorly understood. Studies comparing the functional selectivities of neurons within the early visual areas have found that there are ... ...

Abstract	Functional specialization within the extrastriate areas of the ventral pathway associated with visual form analysis is poorly understood. Studies comparing the functional selectivities of neurons within the early visual areas have found that there are more similar than different between the areas. We simultaneously imaged visually evoked activation over regions of V2 and V4 and parametrically varied three visual attributes for which selectivity exists in both areas: color, orientation, and size. We found that color selective regions were observed in both areas and were of similar size and spatial distribution. However, two major areal distinctions were observed: V4 contained a greater number and diversity of color-specific regions than V2 and exhibited a higher degree of overlap between domains for different functional attributes. In V2, size and color regions were largely segregated from orientation domains, whereas in V4 both color and size regions overlapped considerably with orientation regions. Our results suggest that higher-order composite selectivities in the extrastriate cortex may arise organically from the interactions afforded by an overlap of functional domains for lower order selectivities.
Language	English
Publishing date	2017-05-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2781943-7
ISSN	2329-4248 ; 2329-423X
ISSN (online)	2329-4248
ISSN	2329-423X
DOI	10.1117/1.NPh.4.3.031216
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Article: Contextual modulation revealed by optical imaging exhibits figural asymmetry in macaque V1 and V2.

Zarella, Mark D / Ts'o, Daniel Y

Eye and brain

2017 Volume 9, Page(s) 1–12

Abstract: Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the ... ...

Abstract	Neurons in early visual cortical areas are influenced by stimuli presented well beyond the confines of their classical receptive fields, endowing them with the ability to encode fine-scale features while also having access to the global context of the visual scene. This property can potentially define a role for the early visual cortex to contribute to a number of important visual functions, such as surface segmentation and figure-ground segregation. It is unknown how extraclassical response properties conform to the functional architecture of the visual cortex, given the high degree of functional specialization in areas V1 and V2. We examined the spatial relationships of contextual activations in macaque V1 and V2 with intrinsic signal optical imaging. Using figure-ground stimulus configurations defined by orientation or motion, we found that extraclassical modulation is restricted to the cortical representations of the figural component of the stimulus. These modulations were positive in sign, suggesting a relative enhancement in neuronal activity that may reflect an excitatory influence. Orientation and motion cues produced similar patterns of activation that traversed the functional subdivisions of V2. The asymmetrical nature of the enhancement demonstrated the capacity for visual cortical areas as early as V1 to contribute to figure-ground segregation, and the results suggest that this information can be extracted from the population activity constrained only by retinotopy, and not the underlying functional organization.
Language	English
Publishing date	2017-04-11
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2587460-3
ISSN	1179-2744
ISSN	1179-2744
DOI	10.2147/EB.S105609
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Article: Cue combination encoding via contextual modulation of V1 and V2 neurons.

Zarella, Mark D / Ts'o, Daniel Y

Eye and brain

2016 Volume 8, Page(s) 177–193

Abstract: Neurons in early visual cortical areas encode the local properties of a stimulus in a number of different feature dimensions such as color, orientation, and motion. It has been shown, however, that stimuli presented well beyond the confines of the ... ...

Abstract	Neurons in early visual cortical areas encode the local properties of a stimulus in a number of different feature dimensions such as color, orientation, and motion. It has been shown, however, that stimuli presented well beyond the confines of the classical receptive field can augment these responses in a way that emphasizes these local attributes within the greater context of the visual scene. This mechanism imparts global information to cells that are otherwise considered local feature detectors and can potentially serve as an important foundation for surface segmentation, texture representation, and figure-ground segregation. The role of early visual cortex toward these functions remains somewhat of an enigma, as it is unclear how surface segmentation cues are integrated from multiple feature dimensions. We examined the impact of orientation- and motion-defined surface segmentation cues in V1 and V2 neurons using a stimulus in which the two features are completely separable. We find that, although some cells are modulated in a cue-invariant manner, many cells are influenced by only one cue or the other. Furthermore, cells that are modulated by both cues tend to be more strongly affected when both cues are presented together than when presented individually. These results demonstrate two mechanisms by which cue combinations can enhance salience. We find that feature-specific populations are more frequently encountered in V1, while cue additivity is more prominent in V2. These results highlight how two strongly interconnected areas at different stages in the cortical hierarchy can potentially contribute to scene segmentation.
Language	English
Publishing date	2016-10-21
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2587460-3
ISSN	1179-2744
ISSN	1179-2744
DOI	10.2147/EB.S105616
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Article ; Online: Specificity of V1-V2 orientation networks in the primate visual cortex.

Roe, Anna W / Ts'o, Daniel Y

Cortex; a journal devoted to the study of the nervous system and behavior

2015 Volume 72, Page(s) 168–178

Abstract: The computation of texture and shape involves integration of features of various orientations. Orientation networks within V1 tend to involve cells which share similar orientation selectivity. However, emergent properties in V2 require the integration of ...

Abstract	The computation of texture and shape involves integration of features of various orientations. Orientation networks within V1 tend to involve cells which share similar orientation selectivity. However, emergent properties in V2 require the integration of multiple orientations. We now show that, unlike interactions within V1, V1-V2 orientation interactions are much less synchronized and are not necessarily orientation dependent. We find V1-V2 orientation networks are of two types: a more tightly synchronized, orientation-preserving network and a less synchronized orientation-diverse network. We suggest that such diversity of V1-V2 interactions underlies the spatial and functional integration required for computation of higher order contour and shape in V2.
MeSH term(s)	Animals ; Brain Mapping ; Macaca fascicularis ; Nerve Net/physiology ; Neurons/physiology ; Orientation/physiology ; Photic Stimulation ; Visual Cortex/physiology ; Visual Pathways/physiology ; Visual Perception/physiology
Language	English
Publishing date	2015-07-22
Publishing country	Italy
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	280622-8
ISSN	1973-8102 ; 0010-9452
ISSN (online)	1973-8102
ISSN	0010-9452
DOI	10.1016/j.cortex.2015.07.007
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Article ; Online: Whither the hypercolumn?

Ts'o, Daniel Y / Zarella, Mark / Burkitt, Guy

The Journal of physiology

2009 Volume 587, Issue Pt 12, Page(s) 2791–2805

Abstract: Among the crowning achievements of Hubel and Wiesel's highly influential studies on primary visual cortex is the description of the cortical hypercolumn, a set of cortical columns with functional properties spanning a particular parameter space. This ... ...

Abstract	Among the crowning achievements of Hubel and Wiesel's highly influential studies on primary visual cortex is the description of the cortical hypercolumn, a set of cortical columns with functional properties spanning a particular parameter space. This fundamental concept laid the groundwork for the notion of a modular sensory cortex, canonical cortical circuits and an understanding of visual field coverage beyond simple retinotopy. Surprisingly, the search for and description of analogous hypercolumnar organizations in other cortical areas to date has been limited. In the present work, we have applied the hypercolumn concept to the functional organization of the second visual area, V2. We found it important to separate out the original definition of the hypercolumn from other associated observations and concepts, not all of which are applicable to V2. We present results indicating that, as in V1, the V2 hypercolumns for orientation and binocular interaction (disparity) run roughly orthogonal to each other. We quantified the 'nearest neighbour' periodicities for the hypercolumns for ocular dominance, orientation, colour and disparity, and found a marked similarity in the periodicities of all of these hypercolumns, both across hypercolumn type and across visual areas V1 and V2. The results support an underlying common mechanism that constrains the anatomical extent of hypercolumn systems, and highlight the original definition of the cortical hypercolumn.
MeSH term(s)	Algorithms ; Animals ; Brain Mapping ; Electrophysiology ; Models, Anatomic ; Retina/physiology ; Vision Disparity/physiology ; Visual Cortex/anatomy & histology ; Visual Cortex/physiology ; Visual Pathways/anatomy & histology ; Visual Pathways/physiology
Language	English
Publishing date	2009-06-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2009.171082
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Article ; Online: Retinal intrinsic optical signals in a cat model of primary congenital glaucoma.

Schallek, Jesse B / McLellan, Gillian J / Viswanathan, Suresh / Ts'o, Daniel Y

Investigative ophthalmology & visual science

2012 Volume 53, Issue 4, Page(s) 1971–1981

Abstract: Purpose: To examine the impact of reduced inner retinal function and breed on intrinsic optical signals in cats.: Methods: Retinal intrinsic optical signals were recorded from anesthetized cats with a modified fundus camera. Near infrared light (NIR, ...

Abstract	Purpose: To examine the impact of reduced inner retinal function and breed on intrinsic optical signals in cats. Methods: Retinal intrinsic optical signals were recorded from anesthetized cats with a modified fundus camera. Near infrared light (NIR, 700-900 nm) was used to illuminate the retina while a charge-coupled device (CCD) camera captured the NIR reflectance of the retina. Visible stimuli (540 nm) evoked patterned changes in NIR retinal reflectance. NIR intrinsic signals were compared across three subject groups: two Siamese cats with primary congenital glaucoma (PCG), a control Siamese cat without glaucoma, and a control group of seven normally pigmented cats. Intraocular pressure (IOP), pattern electroretinogram, and optical coherence tomography measurements were evaluated to confirm the inner retinal deficit in PCG cats. Results: Stimulus-evoked, NIR retinal reflectance signals were observed in PCG cats despite severe degeneration of the nerve fiber layer and inner retinal function. The time course, spectral dependence, and spatial profile of signals imaged in PCG cats were similar to signals measured from normal and Siamese control cats. Conclusions: Despite increased IOP, reduced nerve fiber layer thickness and ganglion cell function, intrinsic optical signals persist in cats affected with PCG. The mechanisms giving rise to intrinsic signals remain despite inner retinal damage. Signal strength was reduced in all Siamese cats compared to controls, suggesting that reduced intrinsic signals in PCG cats represent a difference between breeds rather than loss of ganglion cells. These results corroborated previous findings that retinal ganglion cells are not the dominant source of intrinsic optical signals of the retina.
MeSH term(s)	Animals ; Cats ; Disease Models, Animal ; Electroretinography ; Female ; Fluorescein Angiography ; Fundus Oculi ; Glaucoma/congenital ; Glaucoma/diagnosis ; Glaucoma/physiopathology ; Intraocular Pressure ; Photic Stimulation ; Retina/pathology ; Retina/physiopathology ; Tomography, Optical Coherence
Language	English
Publishing date	2012-04-18
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.11-8299
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Article: Color processing in macaque striate cortex: electrophysiological properties.

Landisman, Carole E / Ts'o, Daniel Y

Journal of neurophysiology

2002 Volume 87, Issue 6, Page(s) 3138–3151

Abstract: We have shown in the accompanying paper that optical imaging of macaque striate cortex reveals patches that are preferentially activated by equiluminant chromatic gratings compared with luminance gratings. These imaged color patches are highly correlated, ...

Abstract	We have shown in the accompanying paper that optical imaging of macaque striate cortex reveals patches that are preferentially activated by equiluminant chromatic gratings compared with luminance gratings. These imaged color patches are highly correlated, although not always in one-to-one correspondence, with the cytochrome-oxidase (CO) blobs. In the present study, we have investigated the electrophysiological properties of neurons in the imaged color patches and the CO blobs. Our results indicate that individual blobs tend to contain cells of only one type of color opponency: either red/green or blue/yellow. Individual imaged color patches, however, can bridge blobs of similar opponency or differing opponency. When imaged color patches contain two blobs of differing opponency, the cells in the bridge region exhibit mixed color properties that are not opponent along the two cardinal color axes (either red/green or blue/yellow). Two blobs within a single imaged color patch receive input from the same eye or from different eyes. In the latter case, the bridge region between blobs contains binocular cells that are color selective. Because the cells recorded in imaged color patches were more color selective and unoriented than cells outside of color patches, color properties appear to be organized in a clustered and segregated fashion in primate V1.
MeSH term(s)	Animals ; Brain Mapping ; Color Perception/physiology ; Electron Transport Complex IV/analysis ; Electron Transport Complex IV/physiology ; Electrophysiology ; Macaca fascicularis ; Neurons/enzymology ; Photic Stimulation ; Visual Cortex/physiology ; Visual Fields/physiology
Chemical Substances	Electron Transport Complex IV (EC 1.9.3.1)
Language	English
Publishing date	2002-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00957.1999
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Article: Color processing in macaque striate cortex: relationships to ocular dominance, cytochrome oxidase, and orientation.

Landisman, Carole E / Ts'o, Daniel Y

Journal of neurophysiology

2002 Volume 87, Issue 6, Page(s) 3126–3137

Abstract: We located clusters of color-selective neurons in macaque striate cortex, as mapped with optical imaging and confirmed with electrophysiological recordings. By comparing responses to an equiluminant red/green stimulus versus a high-contrast luminance ... ...

Abstract	We located clusters of color-selective neurons in macaque striate cortex, as mapped with optical imaging and confirmed with electrophysiological recordings. By comparing responses to an equiluminant red/green stimulus versus a high-contrast luminance stimulus, we were able to reveal a patchy distribution of color selectivity. Other color imaging protocols, when compared with electrophysiological data, did not reliably indicate the location of functional structures. The imaged color patches were compared with other known functional subdivisions of striate cortex. There was a high degree of overlap of the color patches with the cytochrome-oxidase (CO) blobs. The patches were often larger than a single blob in size, however, and in some instances spanned two neighboring blobs. More than one-half (56%) of the color-selective patches seen in optical imaging were not confined to one ocular dominance (OD) column. Almost one-quarter of color patches (23%) extended across OD columns to encompass two blobs of different eye preference. We also compared optical images of orientation selectivity to maps of color selectivity. Results indicate that the layout of orientation and color selectivity are not directly related. Specifically, despite having similar scales and distributions, the maps of orientation and color selectivity were not in consistent alignment or registration. Further, we find that the maps of color selectivity and of orientation are each only loosely related to maps of OD. This description stands in contrast to a common depiction of color-selective regions as identical to CO blobs, appearing as pegs in the centers of OD columns in the classical "ice cube" model. These results concerning the pattern of color selectivity in V1 support the view (put forth in previous imaging studies of the organization of orientation and ocular dominance) that there is not a fundamental registration of functional hypercolumns in V1.
MeSH term(s)	Animals ; Brain Mapping ; Color Perception/physiology ; Electron Transport Complex IV/analysis ; Electron Transport Complex IV/physiology ; Electrophysiology ; Macaca fascicularis ; Neurons/enzymology ; Orientation/physiology ; Photic Stimulation ; Visual Cortex/physiology
Chemical Substances	Electron Transport Complex IV (EC 1.9.3.1)
Language	English
Publishing date	2002-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
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Article ; Online: Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases.

Gut

2022 Volume 72, Issue 2, Page(s) 325–337

Abstract: Objective: Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of ... ...

Abstract	Objective: Programmed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate the effect of interleukin 10 (IL-10) blockade on endogenous T cell and chimeric antigen receptor T (CAR-T) cell antitumour function in CRLM slice cultures. Design: We created organotypic slice cultures from human CRLM (n=38 patients' tumours) and tested the antitumour effects of a neutralising antibody against IL-10 (αIL-10) both alone as treatment and in combination with exogenously administered carcinoembryonic antigen (CEA)-specific CAR-T cells. We evaluated slice cultures with single and multiplex immunohistochemistry, in situ hybridisation, single-cell RNA sequencing, reverse-phase protein arrays and time-lapse fluorescent microscopy. Results: αIL-10 generated a 1.8-fold increase in T cell-mediated carcinoma cell death in human CRLM slice cultures. αIL-10 significantly increased proportions of CD8 Conclusion: Neutralising the effects of IL-10 in human CRLM has therapeutic potential as a stand-alone treatment and to augment the function of adoptively transferred CAR-T cells.
MeSH term(s)	Animals ; Humans ; Mice ; Carcinoembryonic Antigen/immunology ; Carcinoma/immunology ; Carcinoma/secondary ; CD8-Positive T-Lymphocytes/immunology ; Colorectal Neoplasms/pathology ; Immunotherapy, Adoptive ; Interleukin-10/antagonists & inhibitors ; Liver Neoplasms/immunology ; Liver Neoplasms/secondary ; Lymphocyte Activation ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; Receptors, Interleukin-10/antagonists & inhibitors ; Antibodies, Blocking/immunology
Chemical Substances	Carcinoembryonic Antigen ; Interleukin-10 (130068-27-8) ; Receptors, Antigen, T-Cell ; Receptors, Chimeric Antigen ; Receptors, Interleukin-10 ; Antibodies, Blocking
Language	English
Publishing date	2022-06-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2021-325808
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