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Article ; Online: Impaired Direction Selectivity in the Nucleus of the Optic Tract of Albino Mice.

Montijn, Jorrit S / Riguccini, Valentina / Levelt, Christiaan N / Heimel, J Alexander

Investigative ophthalmology & visual science

2023 Volume 64, Issue 11, Page(s) 9

Abstract: Purpose: Human albinos have a low visual acuity. This is partially due to the presence of spontaneous erroneous eye movements called pendular nystagmus. This nystagmus is present in other albino vertebrates and has been hypothesized to be caused by ... ...

Abstract	Purpose: Human albinos have a low visual acuity. This is partially due to the presence of spontaneous erroneous eye movements called pendular nystagmus. This nystagmus is present in other albino vertebrates and has been hypothesized to be caused by aberrant wiring of retinal ganglion axons to the nucleus of the optic tract (NOT), a part of the accessory optic system involved in the optokinetic response to visual motion. The NOT in pigmented rodents is preferentially responsive to ipsiversive motion (i.e., motion in the contralateral visual field in the temporonasal direction). We compared the response to visual motion in the NOT of albino and pigmented mice to understand if motion coding and preference are impaired in the NOT of albino mice. Methods: We recorded neuronal spiking activity with Neuropixels probes in the visual cortex and NOT in C57BL/6JRj mice (pigmented) and DBA/1JRj mice with oculocutaneous albinism (albino). Results: We found that in pigmented mice, NOT is retinotopically organized, and neurons are direction tuned, whereas in albino mice, neuronal tuning is severely impaired. Neurons in the NOT of albino mice do not have a preference for ipsiversive movement. In contrast, neuronal tuning in visual cortex was preserved in albino mice and did not differ significantly from the tuning in pigmented mice. Conclusions: We propose that excessive interhemispheric crossing of retinal projections in albinos may cause the disrupted left/right direction encoding we found in NOT. This, in turn, impairs the normal horizontal optokinetic reflex and leads to pendular albino nystagmus.
MeSH term(s)	Animals ; Mice ; Albinism ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Nystagmus, Optokinetic ; Nystagmus, Pathologic ; Pretectal Region ; Retinal Ganglion Cells ; Visual Cortex ; Visual Pathways
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Journal Article ; 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.64.11.9
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Article ; Online: Amblyopia: The Thalamus Is a No-Go Area for Visual Acuity.

Seignette, Koen / Levelt, Christiaan N

Current biology : CB

2018 Volume 28, Issue 12, Page(s) R709–R712

Abstract: When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits. ...

Abstract	When one eye does not function well during development, the visual cortex becomes less responsive to it and visual acuity declines. New research suggests that reduced response strength and deteriorating acuity occur in separate circuits.
MeSH term(s)	Amblyopia ; Animals ; Dominance, Ocular ; Mice ; Thalamus ; Visual Acuity ; Visual Cortex
Language	English
Publishing date	2018-06-18
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2018.04.081
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Zs.A 3208: Show issues

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Article ; Online: Thalamic regulation of ocular dominance plasticity in adult visual cortex.

Qin, Yi / Ahmadlou, Mehran / Suhai, Samuel / Neering, Paul / de Kraker, Leander / Heimel, J Alexander / Levelt, Christiaan N

eLife

2023 Volume 12

Abstract: Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral ... ...

Abstract	Experience-dependent plasticity in the adult visual system is generally thought of as a cortical process. However, several recent studies have shown that perceptual learning or monocular deprivation can also induce plasticity in the adult dorsolateral geniculate nucleus (dLGN) of the thalamus. How plasticity in the thalamus and cortex interact in the adult visual system is ill-understood. To assess the influence of thalamic plasticity on plasticity in primary visual cortex (V1), we made use of our previous finding that during the critical period ocular dominance (OD) plasticity occurs in dLGN and requires thalamic synaptic inhibition. Using multielectrode recordings we find that this is also true in adult mice, and that in the absence of thalamic inhibition and plasticity, OD plasticity in adult V1 is absent. To study the influence of V1 on thalamic plasticity, we silenced V1 and show that during the critical period, but not in adulthood, the OD shift in dLGN is partially caused by feedback from V1. We conclude that during adulthood the thalamus plays an unexpectedly dominant role in experience-dependent plasticity in V1. Our findings highlight the importance of considering the thalamus as a potential source of plasticity in learning events that are typically thought of as cortical processes.
MeSH term(s)	Mice ; Animals ; Dominance, Ocular ; Thalamus/physiology ; Visual Cortex/physiology ; Geniculate Bodies/physiology ; Inhibition, Psychological ; Neuronal Plasticity/physiology
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.88124
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Article ; Online: Experience shapes chandelier cell function and structure in the visual cortex.

Seignette, Koen / Jamann, Nora / Papale, Paolo / Terra, Huub / Porneso, Ralph O / de Kraker, Leander / van der Togt, Chris / van der Aa, Maaike / Neering, Paul / Ruimschotel, Emma / Roelfsema, Pieter R / Montijn, Jorrit S / Self, Matthew W / Kole, Maarten H P / Levelt, Christiaan N

eLife

2024 Volume 12

Abstract: Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we ... ...

Abstract	Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modeling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.
MeSH term(s)	Animals ; Mice ; Neurons ; Pyramidal Cells ; Visual Cortex ; Interneurons ; Arousal
Language	English
Publishing date	2024-01-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.91153
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Article ; Online: A parameter-free statistical test for neuronal responsiveness.

Montijn, Jorrit S / Seignette, Koen / Howlett, Marcus H / Cazemier, J Leonie / Kamermans, Maarten / Levelt, Christiaan N / Heimel, J Alexander

eLife

2021 Volume 10

Abstract: Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based ... ...

Abstract	Neurophysiological studies depend on a reliable quantification of whether and when a neuron responds to stimulation. Simple methods to determine responsiveness require arbitrary parameter choices, such as binning size, while more advanced model-based methods require fitting and hyperparameter tuning. These parameter choices can change the results, which invites bad statistical practice and reduces the replicability. New recording techniques that yield increasingly large numbers of cells would benefit from a test for cell-inclusion that requires no manual curation. Here, we present the parameter-free ZETA-test, which outperforms t-tests, ANOVAs, and renewal-process-based methods by including more cells at a similar false-positive rate. We show that our procedure works across brain regions and recording techniques, including calcium imaging and Neuropixels data. Furthermore, in illustration of the method, we show in mouse visual cortex that (1) visuomotor-mismatch and spatial location are encoded by different neuronal subpopulations and (2) optogenetic stimulation of VIP cells leads to early inhibition and subsequent disinhibition.
MeSH term(s)	Animals ; Male ; Mice ; Neural Inhibition/physiology ; Neurons/physiology ; Optogenetics ; Visual Cortex/physiology
Language	English
Publishing date	2021-09-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.71969
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Article ; Online: Somatostatin interneurons restrict cell recruitment to retinally driven spontaneous activity in the developing cortex.

Leighton, Alexandra H / Cheyne, Juliette E / Houwen, Gerrit J / Maldonado, Paloma P / De Winter, Fred / Levelt, Christiaan N / Lohmann, Christian

Cell reports

2021 Volume 36, Issue 1, Page(s) 109316

Abstract: During early development, before the eyes open, synaptic refinement of sensory networks depends on activity generated by developing neurons themselves. In the mouse visual system, retinal cells spontaneously depolarize and recruit downstream neurons to ... ...

Abstract	During early development, before the eyes open, synaptic refinement of sensory networks depends on activity generated by developing neurons themselves. In the mouse visual system, retinal cells spontaneously depolarize and recruit downstream neurons to bursts of activity, where the number of recruited cells determines the resolution of synaptic retinotopic refinement. Here we show that during the second post-natal week in mouse visual cortex, somatostatin (SST)-expressing interneurons control the recruitment of cells to retinally driven spontaneous activity. Suppressing SST interneurons increases cell participation and allows events to spread farther along the cortex. During the same developmental period, a second type of high-participation, retina-independent event occurs. During these events, cells receive such large excitatory charge that inhibition is overwhelmed and large parts of the cortex participate in each burst. These results reveal a role of SST interneurons in restricting retinally driven activity in the visual cortex, which may contribute to the refinement of retinotopy.
MeSH term(s)	Animals ; Animals, Newborn ; Interneurons/physiology ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Neural Inhibition/physiology ; Retina/physiology ; Somatostatin/metabolism ; Synapses/physiology ; Visual Cortex/growth & development ; Mice
Chemical Substances	Somatostatin (51110-01-1)
Language	English
Publishing date	2021-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2021.109316
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Article ; Online: Inhibitory interneurons in visual cortical plasticity.

van Versendaal, Daniëlle / Levelt, Christiaan N

Cellular and molecular life sciences : CMLS

2016 Volume 73, Issue 19, Page(s) 3677–3691

Abstract: For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, ...

Abstract	For proper maturation of the neocortex and acquisition of specific functions and skills, exposure to sensory stimuli is vital during critical periods of development when synaptic connectivity is highly malleable. To preserve reliable cortical processing, it is essential that these critical periods end after which learning becomes more conditional and active interaction with the environment becomes more important. How these age-dependent forms of plasticity are regulated has been studied extensively in the primary visual cortex. This has revealed that inhibitory innervation plays a crucial role and that a temporary decrease in inhibition is essential for plasticity to take place. Here, we discuss how different interneuron subsets regulate plasticity during different stages of cortical maturation. We propose a theory in which different interneuron subsets select the sources of neuronal input that undergo plasticity.
MeSH term(s)	Action Potentials/physiology ; Animals ; Humans ; Interneurons/physiology ; Neural Inhibition/physiology ; Neuronal Plasticity/physiology ; Retina/pathology ; Visual Cortex/physiology
Language	English
Publishing date	2016-05-18
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-016-2264-4
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Article ; Online: Critical-period plasticity in the visual cortex.

Levelt, Christiaan N / Hübener, Mark

Annual review of neuroscience

2012 Volume 35, Page(s) 309–330

Abstract: In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the ... ...

Abstract	In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.
MeSH term(s)	Aging/physiology ; Animals ; Critical Period (Psychology) ; Dominance, Ocular/physiology ; Humans ; Models, Neurological ; Neural Inhibition/physiology ; Neuronal Plasticity/physiology ; Signal Transduction/physiology ; Synaptic Transmission/physiology ; Visual Cortex/growth & development ; Visual Cortex/physiology
Language	English
Publishing date	2012
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	282459-0
ISSN	1545-4126 ; 0147-006X
ISSN (online)	1545-4126
ISSN	0147-006X
DOI	10.1146/annurev-neuro-061010-113813
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Article ; Online: Synaptotagmin-2 is a reliable marker for parvalbumin positive inhibitory boutons in the mouse visual cortex.

Sommeijer, Jean-Pierre / Levelt, Christiaan N

PloS one

2012 Volume 7, Issue 4, Page(s) e35323

Abstract: Background: Inhibitory innervation by parvalbumin (PV) expressing interneurons has been implicated in the onset of the sensitive period of visual plasticity. Immunohistochemical analysis of the development and plasticity of these inhibitory inputs is ... ...

Abstract	Background: Inhibitory innervation by parvalbumin (PV) expressing interneurons has been implicated in the onset of the sensitive period of visual plasticity. Immunohistochemical analysis of the development and plasticity of these inhibitory inputs is difficult because PV expression is low in young animals and strongly influenced by neuronal activity. Moreover, the synaptic boutons that PV neurons form onto each other cannot be distinguished from the innervated cell bodies by immunostaining for this protein because it is present throughout the cells. These problems call for the availability of a synaptic, activity-independent marker for PV+ inhibitory boutons that is expressed before sensitive period onset. We investigated whether synaptotagmin-2 (Syt2) fulfills these properties in the visual cortex. Syt2 is a synaptic vesicle protein involved in fast Ca(2+) dependent neurotransmitter release. Its mRNA expression follows a pattern similar to that of PV throughout the brain and is present in 30-40% of hippocampal PV expressing basket cells. Up to now, no quantitative analyses of Syt2 expression in the visual cortex have been carried out. Methodology/principal findings: We used immunohistochemistry to analyze colocalization of Syt2 with multiple interneuron markers including vesicular GABA transporter VGAT, calbindin, calretinin, somatostatin and PV in the primary visual cortex of mice during development and after dark-rearing. Conclusions/significance: We show that in the adult visual cortex Syt2 is only found in inhibitory, VGAT positive boutons. Practically all Syt2 positive boutons also contain PV and vice versa. During development, Syt2 expression can be detected in synaptic boutons prior to PV and in contrast to PV expression, Syt2 is not down-regulated by dark-rearing. These properties of Syt2 make it an excellent marker for analyzing the development and plasticity of perisomatic inhibitory innervations onto both excitatory and inhibitory neurons in the visual cortex.
MeSH term(s)	Animals ; Calbindin 2 ; Calbindins ; Female ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Parvalbumins/metabolism ; Presynaptic Terminals/metabolism ; S100 Calcium Binding Protein G/analysis ; S100 Calcium Binding Protein G/metabolism ; Somatostatin/analysis ; Somatostatin/metabolism ; Synaptotagmin II/analysis ; Synaptotagmin II/metabolism ; Vesicular Inhibitory Amino Acid Transport Proteins/analysis ; Vesicular Inhibitory Amino Acid Transport Proteins/metabolism ; Visual Cortex/metabolism
Chemical Substances	Calb2 protein, mouse ; Calbindin 2 ; Calbindins ; Parvalbumins ; S100 Calcium Binding Protein G ; Synaptotagmin II ; Vesicular Inhibitory Amino Acid Transport Proteins ; Viaat protein, mouse ; Somatostatin (51110-01-1)
Language	English
Publishing date	2012-04-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0035323
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Article ; Online: SpecSeg is a versatile toolbox that segments neurons and neurites in chronic calcium imaging datasets based on low-frequency cross-spectral power.

de Kraker, Leander / Seignette, Koen / Thamizharasu, Premnath / van den Boom, Bastijn J G / Ferreira Pica, Ildefonso / Willuhn, Ingo / Levelt, Christiaan N / Togt, Chris van der

Cell reports methods

2022 Volume 2, Issue 10, Page(s) 100299

Abstract: Imaging calcium signals in neurons of animals using single- or multi-photon microscopy facilitates the study of coding in large neural populations. Such experiments produce massive datasets requiring powerful methods to extract responses from hundreds of ...

Abstract	Imaging calcium signals in neurons of animals using single- or multi-photon microscopy facilitates the study of coding in large neural populations. Such experiments produce massive datasets requiring powerful methods to extract responses from hundreds of neurons. We present SpecSeg, an open-source toolbox for (1) segmentation of regions of interest (ROIs) representing neuronal structures, (2) inspection and manual editing of ROIs, (3) neuropil correction and signal extraction, and (4) matching of ROIs in sequential recordings. ROI segmentation in SpecSeg is based on temporal cross-correlations of low-frequency components derived by Fourier analysis of each pixel with its neighbors. The approach is user-friendly, intuitive, and insightful and enables ROI detection around neurons or neurites. It works for single- (miniscope) and multi-photon microscopy data, eliminating the need for separate toolboxes. SpecSeg thus provides an efficient and versatile approach for analyzing calcium responses in neuronal structures imaged over prolonged periods of time.
MeSH term(s)	Animals ; Neurites ; Calcium ; Neurons/physiology ; Calcium, Dietary ; Microscopy
Chemical Substances	Calcium (SY7Q814VUP) ; Calcium, Dietary
Language	English
Publishing date	2022-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2667-2375
ISSN (online)	2667-2375
DOI	10.1016/j.crmeth.2022.100299
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