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  1. Article ; Online: Müller Glia in Retinal Development: From Specification to Circuit Integration.

    Tworig, Joshua M / Feller, Marla B

    Frontiers in neural circuits

    2022  Volume 15, Page(s) 815923

    Abstract: Müller glia of the retina share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitter spillover, and robust response to injury. Here we present the molecular factors and signaling ... ...

    Abstract Müller glia of the retina share many features with astroglia located throughout the brain including maintenance of homeostasis, modulation of neurotransmitter spillover, and robust response to injury. Here we present the molecular factors and signaling events that govern Müller glial specification, patterning, and differentiation. Next, we discuss the various roles of Müller glia in retinal development, which include maintaining retinal organization and integrity as well as promoting neuronal survival, synaptogenesis, and phagocytosis of debris. Finally, we review the mechanisms by which Müller glia integrate into retinal circuits and actively participate in neuronal signaling during development.
    MeSH term(s) Astrocytes ; Neurogenesis ; Neuroglia/physiology ; Phagocytosis/physiology ; Retina
    Language English
    Publishing date 2022-02-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2452968-0
    ISSN 1662-5110 ; 1662-5110
    ISSN (online) 1662-5110
    ISSN 1662-5110
    DOI 10.3389/fncir.2021.815923
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Excitatory neurotransmission activates compartmentalized calcium transients in Müller glia without affecting lateral process motility.

    Tworig, Joshua M / Coate, Chandler J / Feller, Marla B

    eLife

    2021  Volume 10

    Abstract: Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here, we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type ... ...

    Abstract Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here, we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia that exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These regions comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.
    MeSH term(s) Animals ; Calcium/analysis ; Calcium/metabolism ; Cell Physiological Phenomena ; Cytosol/chemistry ; Cytosol/physiology ; Ependymoglial Cells/physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Retina/cytology ; Retina/growth & development ; Synaptic Transmission
    Chemical Substances Calcium (SY7Q814VUP)
    Language English
    Publishing date 2021-12-16
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.73202
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Differential Expression Analysis Identifies Candidate Synaptogenic Molecules for Wiring Direction-Selective Circuits in the Retina.

    Tworig, Joshua M / Morrie, Ryan D / Bistrong, Karina / Somaiya, Rachana D / Hsu, Shaw / Liang, Jocelyn / Cornejo, Karen G / Feller, Marla B

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

    2024  Volume 44, Issue 18

    Abstract: An organizational feature of neural circuits is the specificity of synaptic connections. A striking example is the direction-selective (DS) circuit of the retina. There are multiple subtypes of DS retinal ganglion cells (DSGCs) that prefer motion along ... ...

    Abstract An organizational feature of neural circuits is the specificity of synaptic connections. A striking example is the direction-selective (DS) circuit of the retina. There are multiple subtypes of DS retinal ganglion cells (DSGCs) that prefer motion along one of four preferred directions. This computation is mediated by selective wiring of a single inhibitory interneuron, the starburst amacrine cell (SAC), with each DSGC subtype preferentially receiving input from a subset of SAC processes. We hypothesize that the molecular basis of this wiring is mediated in part by unique expression profiles of DSGC subtypes. To test this, we first performed paired recordings from isolated mouse retinas of both sexes to determine that postnatal day 10 (P10) represents the age at which asymmetric synapses form. Second, we performed RNA sequencing and differential expression analysis on isolated P10 ON-OFF DSGCs tuned for either nasal or ventral motion and identified candidates which may promote direction-specific wiring. We then used a conditional knock-out strategy to test the role of one candidate, the secreted synaptic organizer cerebellin-4 (Cbln4), in the development of DS tuning. Using two-photon calcium imaging, we observed a small deficit in directional tuning among ventral-preferring DSGCs lacking Cbln4, though whole-cell voltage-clamp recordings did not identify a significant change in inhibitory inputs. This suggests that Cbln4 does not function primarily via a cell-autonomous mechanism to instruct wiring of DS circuits. Nevertheless, our transcriptomic analysis identified unique candidate factors for gaining insights into the molecular mechanisms that instruct wiring specificity in the DS circuit.
    MeSH term(s) Animals ; Mice ; Retina/metabolism ; Retina/physiology ; Male ; Synapses/physiology ; Synapses/metabolism ; Female ; Retinal Ganglion Cells/metabolism ; Retinal Ganglion Cells/physiology ; Mice, Inbred C57BL ; Amacrine Cells/physiology ; Amacrine Cells/metabolism ; Motion Perception/physiology ; Nerve Net/physiology ; Nerve Net/metabolism ; Visual Pathways/physiology ; Visual Pathways/metabolism
    Language English
    Publishing date 2024-05-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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.1461-23.2024
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The influence of spontaneous and visual activity on the development of direction selectivity maps in mouse retina.

    Tiriac, Alexandre / Bistrong, Karina / Pitcher, Miah N / Tworig, Joshua M / Feller, Marla B

    Cell reports

    2022  Volume 38, Issue 2, Page(s) 110225

    Abstract: In mice, retinal direction selectivity is organized in a map that aligns to the body and gravitational axes of optic flow, and little is known about how this map develops. We find direction selectivity maps are largely present at eye opening and develop ... ...

    Abstract In mice, retinal direction selectivity is organized in a map that aligns to the body and gravitational axes of optic flow, and little is known about how this map develops. We find direction selectivity maps are largely present at eye opening and develop normally in the absence of visual experience. Remarkably, in mice lacking the beta2 subunit of neuronal nicotinic acetylcholine receptors (β2-nAChR-KO), which exhibit drastically reduced cholinergic retinal waves in the first postnatal week, selectivity to horizontal motion is absent while selectivity to vertical motion remains. We tested several possible mechanisms that could explain the loss of horizontal direction selectivity in β2-nAChR-KO mice (wave propagation bias, FRMD7 expression, starburst amacrine cell morphology), but all were found to be intact when compared with WT mice. This work establishes a role for retinal waves in the development of asymmetric circuitry that mediates retinal direction selectivity via an unknown mechanism.
    MeSH term(s) Action Potentials/physiology ; Animals ; Animals, Newborn ; Dendrites/metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL/embryology ; Motion ; Motion Perception/physiology ; Optic Flow/physiology ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism ; Retina/embryology ; Retina/metabolism ; Retinal Ganglion Cells/metabolism ; Synaptic Transmission/physiology ; Visual Acuity/genetics ; Visual Pathways/physiology
    Chemical Substances Receptors, Nicotinic ; nicotinic receptor beta2
    Language English
    Publishing date 2022-01-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.110225
    Database MEDical Literature Analysis and Retrieval System OnLINE

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