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  1. Article ; Online: Involvement of superior colliculus in complex figure detection of mice.

    Cazemier, J Leonie / Haak, Robin / Tran, T K Loan / Hsu, Ann T Y / Husic, Medina / Peri, Brandon D / Kirchberger, Lisa / Self, Matthew W / Roelfsema, Pieter / Heimel, J Alexander

    eLife

    2024  Volume 13

    Abstract: Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been ... ...

    Abstract Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is involved in figure detection based on differences in figure contrast, orientation, and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than for incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.
    MeSH term(s) Animals ; Mice ; Superior Colliculi ; Optogenetics ; Visual Cortex ; Visual Perception
    Language English
    Publishing date 2024-01-25
    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.83708
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. 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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Connectomic Analysis of Brain Networks: Novel Techniques and Future Directions.

    Cazemier, J Leonie / Clascá, Francisco / Tiesinga, Paul H E

    Frontiers in neuroanatomy

    2016  Volume 10, Page(s) 110

    Abstract: Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. "Connectomics" ...

    Abstract Brain networks, localized or brain-wide, exist only at the cellular level, i.e., between specific pre- and post-synaptic neurons, which are connected through functionally diverse synapses located at specific points of their cell membranes. "Connectomics" is the emerging subfield of neuroanatomy explicitly aimed at elucidating the wiring of brain networks with cellular resolution and a quantified accuracy. Such data are indispensable for realistic modeling of brain circuitry and function. A connectomic analysis, therefore, needs to identify and measure the soma, dendrites, axonal path, and branching patterns together with the synapses and gap junctions of the neurons involved in any given brain circuit or network. However, because of the submicron caliber, 3D complexity, and high packing density of most such structures, as well as the fact that axons frequently extend over long distances to make synapses in remote brain regions, creating connectomic maps is technically challenging and requires multi-scale approaches, Such approaches involve the combination of the most sensitive cell labeling and analysis methods available, as well as the development of new ones able to resolve individual cells and synapses with increasing high-throughput. In this review, we provide an overview of recently introduced high-resolution methods, which researchers wanting to enter the field of connectomics may consider. It includes several molecular labeling tools, some of which specifically label synapses, and covers a number of novel imaging tools such as brain clearing protocols and microscopy approaches. Apart from describing the tools, we also provide an assessment of their qualities. The criteria we use assess the qualities that tools need in order to contribute to deciphering the key levels of circuit organization. We conclude with a brief future outlook for neuroanatomic research, computational methods, and network modeling, where we also point out several outstanding issues like structure-function relations and the complexity of neural models.
    Language English
    Publishing date 2016-11-09
    Publishing country Switzerland
    Document type Review ; Journal Article
    ZDB-ID 2452969-2
    ISSN 1662-5129
    ISSN 1662-5129
    DOI 10.3389/fnana.2016.00110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration.

    Schaffer, Ashleigh E / Eggens, Veerle R C / Caglayan, Ahmet Okay / Reuter, Miriam S / Scott, Eric / Coufal, Nicole G / Silhavy, Jennifer L / Xue, Yuanchao / Kayserili, Hulya / Yasuno, Katsuhito / Rosti, Rasim Ozgur / Abdellateef, Mostafa / Caglar, Caner / Kasher, Paul R / Cazemier, J Leonie / Weterman, Marian A / Cantagrel, Vincent / Cai, Na / Zweier, Christiane /
    Altunoglu, Umut / Satkin, N Bilge / Aktar, Fesih / Tuysuz, Beyhan / Yalcinkaya, Cengiz / Caksen, Huseyin / Bilguvar, Kaya / Fu, Xiang-Dong / Trotta, Christopher R / Gabriel, Stacey / Reis, André / Gunel, Murat / Baas, Frank / Gleeson, Joseph G

    Cell

    2014  Volume 157, Issue 3, Page(s) 651–663

    Abstract: Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and ... ...

    Abstract Neurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans.
    MeSH term(s) Animals ; Brain/metabolism ; Brain/pathology ; Cerebellum/growth & development ; Cerebellum/pathology ; Cleavage And Polyadenylation Specificity Factor/genetics ; Cleavage And Polyadenylation Specificity Factor/metabolism ; Female ; Humans ; Male ; Mice ; Models, Molecular ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Pedigree ; Phosphotransferases/genetics ; Phosphotransferases/metabolism ; RNA Splicing ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Saccharomyces cerevisiae/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Zebrafish ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism
    Chemical Substances Cleavage And Polyadenylation Specificity Factor ; Nuclear Proteins ; Transcription Factors ; Zebrafish Proteins ; RNA, Transfer (9014-25-9) ; CLP1 protein, human (EC 2.7.-) ; CLP1 protein, zebrafish (EC 2.7.-) ; Phosphotransferases (EC 2.7.-)
    Language English
    Publishing date 2014-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2014.03.049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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