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Article ; Online: Backward masking in mice requires visual cortex.

Gale, Samuel D / Strawder, Chelsea / Bennett, Corbett / Mihalas, Stefan / Koch, Christof / Olsen, Shawn R

2023 Volume 27, Issue 1, Page(s) 129–136

Abstract: Visual masking can reveal the timescale of perception, but the underlying circuit mechanisms are not understood. Here we describe a backward masking task in mice and humans in which the location of a stimulus is potently masked. Humans report reduced ... ...

Abstract	Visual masking can reveal the timescale of perception, but the underlying circuit mechanisms are not understood. Here we describe a backward masking task in mice and humans in which the location of a stimulus is potently masked. Humans report reduced subjective visibility that tracks behavioral deficits. In mice, both masking and optogenetic silencing of visual cortex (V1) reduce performance over a similar timecourse but have distinct effects on response rates and accuracy. Activity in V1 is consistent with masked behavior when quantified over long, but not short, time windows. A dual accumulator model recapitulates both mouse and human behavior. The model and subjects' performance imply that the initial spikes in V1 can trigger a correct response, but subsequent V1 activity degrades performance. Supporting this hypothesis, optogenetically suppressing mask-evoked activity in V1 fully restores accurate behavior. Together, these results demonstrate that mice, like humans, are susceptible to masking and that target and mask information is first confounded downstream of V1.
MeSH term(s)	Humans ; Mice ; Animals ; Perceptual Masking/physiology ; Visual Cortex/physiology ; Photic Stimulation/methods ; Visual Perception/physiology
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-023-01488-0
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Article ; Online: Single administration of a psychedelic [(R)-DOI] influences coping strategies to an escapable social stress.

Krupp, Kevin T / Yaeger, Jazmine D W / Ledesma, Leighton J / Withanage, Miyuraj Harishchandra Hikkaduwa / Gale, J J / Howe, Chase B / Allen, Trevor J / Sathyanesan, Monica / Newton, Samuel S / Summers, Cliff H

Neuropharmacology

2024 Volume 252, Page(s) 109949

Abstract: Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5- ... ...

Abstract	Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT
Language	English
Publishing date	2024-04-16
Publishing country	England
Document type	Journal Article
ZDB-ID	218272-5
ISSN	1873-7064 ; 0028-3908
ISSN (online)	1873-7064
ISSN	0028-3908
DOI	10.1016/j.neuropharm.2024.109949
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Article ; Online: Distinct cell types in the superficial superior colliculus project to the dorsal lateral geniculate and lateral posterior thalamic nuclei.

Gale, Samuel D / Murphy, Gabe J

Journal of neurophysiology

2018 Volume 120, Issue 3, Page(s) 1286–1292

Abstract: The superficial layers of the superior colliculus (sSC) receive retinal input and project to thalamic regions, the dorsal lateral geniculate (dLGN) and lateral posterior (LP; or pulvinar) nuclei, that convey visual information to cortex. A critical step ... ...

Abstract	The superficial layers of the superior colliculus (sSC) receive retinal input and project to thalamic regions, the dorsal lateral geniculate (dLGN) and lateral posterior (LP; or pulvinar) nuclei, that convey visual information to cortex. A critical step toward understanding the functional impact of sSC neurons on these parallel thalamo-cortical pathways is determining whether different classes of sSC neurons, which are known to respond to different features of visual stimuli, innervate overlapping or distinct thalamic targets. Here, we identified a transgenic mouse line that labels sSC neurons that project to dLGN but not LP. We utilized selective expression of fluorophores and channelrhodopsin in this and previously characterized mouse lines to demonstrate that distinct cell types give rise to sSC projections to dLGN and LP. We further show that the glutamatergic sSC cell type that projects to dLGN also provides input to the sSC cell type that projects to LP. These results clarify the cellular origin of parallel sSC-thalamo-cortical pathways and reveal an interaction between these pathways via local connections within the sSC. NEW & NOTEWORTHY The superficial layers of the superior colliculus (sSC) project to two visual thalamic targets: the dorsal lateral geniculate (dLGN) and lateral posterior (LP) nuclei. We show that distinct excitatory sSC cell types give rise to these projections; stellate cells project to dLGN and wide-field (WF) cells project to LP. Moreover, these pathways interact via a connection within the sSC from stellate to WF cells.
MeSH term(s)	Animals ; Female ; Geniculate Bodies/physiology ; Male ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Neurological ; Neurons/physiology ; Pulvinar/physiology ; Superior Colliculi/physiology ; Visual Pathways/physiology
Language	English
Publishing date	2018-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00248.2018
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Article ; Online: Active Dendritic Properties and Local Inhibitory Input Enable Selectivity for Object Motion in Mouse Superior Colliculus Neurons.

Gale, Samuel D / Murphy, Gabe J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2016 Volume 36, Issue 35, Page(s) 9111–9123

Abstract: Unlabelled: Neurons respond to specific features of sensory stimuli. In the visual system, for example, some neurons respond to motion of small but not large objects, whereas other neurons prefer motion of the entire visual field. Separate neurons ... ...

Abstract	Unlabelled: Neurons respond to specific features of sensory stimuli. In the visual system, for example, some neurons respond to motion of small but not large objects, whereas other neurons prefer motion of the entire visual field. Separate neurons respond equally to local and global motion but selectively to additional features of visual stimuli. How and where does response selectivity emerge? Here, we show that wide-field (WF) cells in retino-recipient layers of the mouse superior colliculus (SC) respond selectively to small moving objects. Moreover, we identify two mechanisms that contribute to this selectivity. First, we show that input restricted to a small portion of the broad dendritic arbor of WF cells is sufficient to trigger dendritic spikes that reliably propagate to the soma/axon. In vivo whole-cell recordings reveal that nearly every action potential evoked by visual stimuli has characteristics of spikes initiated in dendrites. Second, inhibitory input from a different class of SC neuron, horizontal cells, constrains the range of stimuli to which WF cells respond. Horizontal cells respond preferentially to the sudden appearance or rapid movement of large stimuli. Optogenetic reduction of their activity reduces movement selectivity and broadens size tuning in WF cells by increasing the relative strength of responses to stimuli that appear suddenly or cover a large region of space. Therefore, strongly propagating dendritic spikes enable small stimuli to drive spike output in WF cells and local inhibition helps restrict responses to stimuli that are both small and moving. Significance statement: How do neurons respond selectively to some sensory stimuli but not others? In the visual system, a particularly relevant stimulus feature is object motion, which often reveals other animals. Here, we show how specific cells in the superior colliculus, one synapse downstream of the retina, respond selectively to object motion. These wide-field (WF) cells respond strongly to small objects that move slowly anywhere through a large region of space, but not to stationary objects or full-field motion. Action potential initiation in dendrites enables small stimuli to trigger visual responses and inhibitory input from cells that prefer large, suddenly appearing, or quickly moving stimuli restricts responses of WF cells to objects that are small and moving.
MeSH term(s)	Action Potentials/physiology ; Animals ; Biophysics ; Calcium/metabolism ; Channelrhodopsins ; Dendrites/physiology ; Glutamate Decarboxylase/genetics ; Glutamate Decarboxylase/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; In Vitro Techniques ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Motion ; Neurons/classification ; Neurons/cytology ; Neurons/physiology ; Optogenetics ; Patch-Clamp Techniques ; Photic Stimulation ; Receptors, Neurotensin/genetics ; Receptors, Neurotensin/metabolism ; Superior Colliculi/cytology ; Vesicular Inhibitory Amino Acid Transport Proteins/genetics ; Vesicular Inhibitory Amino Acid Transport Proteins/metabolism
Chemical Substances	Channelrhodopsins ; Receptors, Neurotensin ; Vesicular Inhibitory Amino Acid Transport Proteins ; Viaat protein, mouse ; neurotensin type 1 receptor ; Green Fluorescent Proteins (147336-22-9) ; Glutamate Decarboxylase (EC 4.1.1.15) ; glutamate decarboxylase 2 (EC 4.1.1.15) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2016-08-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.0645-16.2016
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Article: A survey of neurophysiological differentiation across mouse visual brain areas and timescales.

Gandhi, Saurabh R / Mayner, William G P / Marshall, William / Billeh, Yazan N / Bennett, Corbett / Gale, Samuel D / Mochizuki, Chris / Siegle, Joshua H / Olsen, Shawn / Tononi, Giulio / Koch, Christof / Arkhipov, Anton

Frontiers in computational neuroscience

2023 Volume 17, Page(s) 1040629

Abstract: Neurophysiological differentiation (ND), a measure of the number of distinct activity states that a neural population visits over a time interval, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely ... ...

Abstract	Neurophysiological differentiation (ND), a measure of the number of distinct activity states that a neural population visits over a time interval, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely been studied in non-invasive human whole-brain recordings where spatial resolution is limited. However, it is likely that perception is supported by discrete neuronal populations rather than the whole brain. Therefore, here we use Neuropixels recordings from the mouse brain to characterize the ND metric across a wide range of temporal scales, within neural populations recorded at single-cell resolution in localized regions. Using the spiking activity of thousands of simultaneously recorded neurons spanning 6 visual cortical areas and the visual thalamus, we show that the ND of stimulus-evoked activity of the entire visual cortex is higher for naturalistic stimuli relative to artificial ones. This finding holds in most individual areas throughout the visual hierarchy. Moreover, for animals performing an image change detection task, ND of the entire visual cortex (though not individual areas) is higher for successful detection compared to failed trials, consistent with the assumed perception of the stimulus. Together, these results suggest that ND computed on cellular-level neural recordings is a useful tool highlighting cell populations that may be involved in subjective perception.
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452964-3
ISSN	1662-5188
ISSN	1662-5188
DOI	10.3389/fncom.2023.1040629
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Article: Development and Evaluation of Ensemble Learning-based Environmental Methane Detection and Intensity Prediction Models.

Majumder, Reek / Pollard, Jacquan / Salek, M Sabbir / Werth, David / Comert, Gurcan / Gale, Adrian / Khan, Sakib Mahmud / Darko, Samuel / Chowdhury, Mashrur

Environmental health insights

2024 Volume 18, Page(s) 11786302241227307

Abstract: The environmental impacts of global warming driven by methane ( ... ...

Abstract	The environmental impacts of global warming driven by methane (CH
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2452946-1
ISSN	1178-6302
ISSN	1178-6302
DOI	10.1177/11786302241227307
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Article ; Online: A survey of neurophysiological differentiation across mouse visual brain areas and timescales

Saurabh R. Gandhi / William G. P. Mayner / William Marshall / Yazan N. Billeh / Corbett Bennett / Samuel D. Gale / Chris Mochizuki / Joshua H. Siegle / Shawn Olsen / Giulio Tononi / Christof Koch / Anton Arkhipov

Frontiers in Computational Neuroscience, Vol

2023 Volume 17

Abstract	Neurophysiological differentiation (ND), a measure of the number of distinct activity states that a neural population visits over a time interval, has been used as a correlate of meaningfulness or subjective perception of visual stimuli. ND has largely been studied in non-invasive human whole-brain recordings where spatial resolution is limited. However, it is likely that perception is supported by discrete neuronal populations rather than the whole brain. Therefore, here we use Neuropixels recordings from the mouse brain to characterize the ND metric across a wide range of temporal scales, within neural populations recorded at single-cell resolution in localized regions. Using the spiking activity of thousands of simultaneously recorded neurons spanning 6 visual cortical areas and the visual thalamus, we show that the ND of stimulus-evoked activity of the entire visual cortex is higher for naturalistic stimuli relative to artificial ones. This finding holds in most individual areas throughout the visual hierarchy. Moreover, for animals performing an image change detection task, ND of the entire visual cortex (though not individual areas) is higher for successful detection compared to failed trials, consistent with the assumed perception of the stimulus. Together, these results suggest that ND computed on cellular-level neural recordings is a useful tool highlighting cell populations that may be involved in subjective perception.
Keywords	visual cortex ; neurophysiological differentiation ; mouse ; Allen Institute for Brain Science ; Neuropixels ; conscious perception ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
Subject code	612
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
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Article ; Online: Distinct representation and distribution of visual information by specific cell types in mouse superficial superior colliculus.

Gale, Samuel D / Murphy, Gabe J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2014 Volume 34, Issue 40, Page(s) 13458–13471

Abstract: The superficial superior colliculus (sSC) occupies a critical node in the mammalian visual system; it is one of two major retinorecipient areas, receives visual cortical input, and innervates visual thalamocortical circuits. Nonetheless, the contribution ...

Abstract	The superficial superior colliculus (sSC) occupies a critical node in the mammalian visual system; it is one of two major retinorecipient areas, receives visual cortical input, and innervates visual thalamocortical circuits. Nonetheless, the contribution of sSC neurons to downstream neural activity and visually guided behavior is unknown and frequently neglected. Here we identified the visual stimuli to which specific classes of sSC neurons respond, the downstream regions they target, and transgenic mice enabling class-specific manipulations. One class responds to small, slowly moving stimuli and projects exclusively to lateral posterior thalamus; another, comprising GABAergic neurons, responds to the sudden appearance or rapid movement of large stimuli and projects to multiple areas, including the lateral geniculate nucleus. A third class exhibits direction-selective responses and targets deeper SC layers. Together, our results show how specific sSC neurons represent and distribute diverse information and enable direct tests of their functional role.
MeSH term(s)	Action Potentials/physiology ; Animals ; Channelrhodopsins ; Excitatory Amino Acid Antagonists/pharmacology ; Female ; GABA Antagonists/pharmacology ; Glutamate Decarboxylase/genetics ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Male ; Mice ; Mice, Transgenic ; Neurons/classification ; Neurons/physiology ; Pyridazines/pharmacology ; Quinoxalines/pharmacology ; Receptors, Neurotensin/genetics ; Receptors, Neurotensin/metabolism ; Superior Colliculi/cytology ; Valine/analogs & derivatives ; Valine/pharmacology ; Vesicular Inhibitory Amino Acid Transport Proteins/genetics ; Vesicular Inhibitory Amino Acid Transport Proteins/metabolism ; Visual Fields/physiology ; Visual Pathways/physiology
Chemical Substances	Channelrhodopsins ; Excitatory Amino Acid Antagonists ; GABA Antagonists ; Luminescent Proteins ; Pyridazines ; Quinoxalines ; Receptors, Neurotensin ; Vesicular Inhibitory Amino Acid Transport Proteins ; Viaat protein, mouse ; neurotensin type 1 receptor ; 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline (118876-58-7) ; Green Fluorescent Proteins (147336-22-9) ; 2-amino-5-phosphopentanoic acid (76326-31-3) ; gabazine (99460MG420) ; Glutamate Decarboxylase (EC 4.1.1.15) ; glutamate decarboxylase 2 (EC 4.1.1.15) ; Valine (HG18B9YRS7)
Language	English
Publishing date	2014-10-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2768-14.2014
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Article ; Online: Target Occupancy and Functional Inhibition of JAK3 and TEC Family Kinases by Ritlecitinib in Healthy Adults: An Open-Label, Phase 1 Study.

Martin, David A / Telliez, Jean-Baptiste / Pleasic-Williams, Susan / Zhang, Ying / Tierney, Brendan / Blatnik, Matthew / Gale, Jeremy D / Banfield, Chris / Zhou, Yifan / Lejeune, Alexandre / Zwillich, Samuel H / Stevens, Erin / Tiwari, Neeraj / Kieras, Elizabeth / Karanam, Ashwin

Journal of clinical pharmacology

2023 Volume 64, Issue 1, Page(s) 67–79

Abstract: ... cell activation, following treatment with anti-immunoglobulin D. Eight participants received one 50 mg ...

Abstract	Ritlecitinib is a small molecule in clinical development that covalently and irreversibly inhibits Janus kinase 3 (JAK3) and the TEC family of kinases (BTK, BMX, ITK, TXK, and TEC). This phase 1, open-label, parallel-group study assessed target occupancy and functional effects of ritlecitinib on JAK3 and TEC family kinases in healthy participants aged 18-60 years who received 50 or 200 mg single doses of ritlecitinib on day 1. Blood samples to assess ritlecitinib pharmacokinetics, target occupancy, and pharmacodynamics were collected over 48 hours. Target occupancy was assessed using mass spectroscopy. Functional inhibition of JAK3-dependent signaling was measured by the inhibition of the phosphorylation of its downstream target signal transducer and activator of transcription 5 (pSTAT5), following activation by interleukin 15 (IL-15). The functional inhibition of Bruton's tyrosine kinase (BTK)-dependent signaling was measured by the reduction in the upregulation of cluster of differentiation 69 (CD69), an early marker of B-cell activation, following treatment with anti-immunoglobulin D. Eight participants received one 50 mg ritlecitinib dose and 8 participants received one 200 mg dose. Ritlecitinib plasma exposure increased in an approximately dose-proportional manner from 50 to 200 mg. The maximal median JAK3 target occupancy was 72% for 50 mg and 64% for 200 mg. Ritlecitinib 50 mg had >94% maximal target occupancy of all TEC kinases, except BMX (87%), and 200 mg had >97% for all TEC kinases. For BTK and TEC, ritlecitinib maintained high target occupancy throughout a period of 48 hours. Ritlecitinib reduced pSTAT5 levels following IL-15- and BTK-dependent signaling in a dose-dependent manner. These target occupancy and functional assays demonstrate the dual inhibition of the JAK3- and BTK-dependent pathways by ritlecitinib. Further studies are needed to understand the contribution to clinical effects of inhibiting these pathways.
MeSH term(s)	Humans ; Interleukin-15 ; Janus Kinase 3 ; Agammaglobulinaemia Tyrosine Kinase ; Signal Transduction ; Protein Kinase Inhibitors/pharmacology ; Immunologic Factors
Chemical Substances	Interleukin-15 ; Janus Kinase 3 (EC 2.7.10.2) ; Agammaglobulinaemia Tyrosine Kinase (EC 2.7.10.2) ; Protein Kinase Inhibitors ; Immunologic Factors ; JAK3 protein, human (EC 2.7.10.2)
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188980-1
ISSN	1552-4604 ; 0091-2700 ; 0021-9754
ISSN (online)	1552-4604
ISSN	0091-2700 ; 0021-9754
DOI	10.1002/jcph.2347
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Article ; Online: Assessing functional reorganization in visual cortex with simulated retinal lesions.

Brown, Holly D H / Gouws, André D / Vernon, Richard J W / Lawrence, Samuel J D / Donnelly, Gemma / Gill, Lorraine / Gale, Richard P / Baseler, Heidi A / Morland, Antony B

Brain structure & function

2021 Volume 226, Issue 9, Page(s) 2855–2867

Abstract: Macular degeneration (MD) causes central vision loss, removing input to corresponding representations in the primary visual cortex. There is disagreement concerning whether the cortical regions deprived of input can remain responsive, and the source of ... ...

Abstract	Macular degeneration (MD) causes central vision loss, removing input to corresponding representations in the primary visual cortex. There is disagreement concerning whether the cortical regions deprived of input can remain responsive, and the source of reported cortical responses is still debated. To simulate MD in controls, normally sighted participants viewed a bright central disk to adapt the retina, creating a transient 'retinal lesion' during a functional MRI experiment. Participants viewed blocks of faces, scrambled faces and uniform grey stimuli, either passively or whilst performing a one-back task. To assess the impact of the simulated lesion, participants repeated the paradigm using a more conventional mean luminance simulated scotoma without adaptation. Our results suggest our attempt to create a more realistic simulation of a lesion did not impact on responses in the representation of the simulated lesion. While most participants showed no evidence of stimulus-driven activation within the lesion representation, a few individuals (22%) exhibited responses similar to a participant with juvenile MD who completed the same paradigm (without adaptation). Reliability analysis showed that responses in the representation of the lesion were generally consistent irrespective of whether positive or negative. We provide some evidence that peripheral visual stimulation can also produce responses in central representations in controls while performing a task. This suggests that the 'signature of reorganization of visual processing', is not found solely in patients with retinal lesions, consistent with the idea that activity may be driven by unmasked top-down feedback.
MeSH term(s)	Humans ; Macular Degeneration ; Reproducibility of Results ; Retina/pathology ; Retina/physiopathology ; Scotoma ; Visual Cortex/diagnostic imaging ; Visual Perception
Language	English
Publishing date	2021-09-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2273162-3
ISSN	1863-2661 ; 1863-2653
ISSN (online)	1863-2661
ISSN	1863-2653
DOI	10.1007/s00429-021-02366-w
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