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  • 1
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 25, No. 20 ( 2005-05-18), p. 5066-5078
    Kurzfassung: In addition to mediating sexual maturation and reproduction through stimulation of classical intracellular receptors that bind DNA and regulate gene expression, estradiol is also thought to influence various brain functions by acting on receptors localized to the neuronal membrane surface. Many intracellular signaling pathways and modulatory proteins are affected by estradiol via this unconventional route, including regulation of the transcription factor cAMP response element-binding protein (CREB). However, the mechanisms by which estradiol acts at the membrane surface are poorly understood. Because both estradiol and CREB have been implicated in regulating learning and memory, we characterized the effects of estradiol on this transcription factor in cultured rat hippocampal neurons. Within minutes of administration, estradiol triggered mitogen-activated protein kinase (MAPK)-dependent CREB phosphorylation in unstimulated neurons. Furthermore, after brief depolarization, estradiol attenuated L-type calcium channel-mediated CREB phosphorylation. Thus, estradiol exhibited both positive and negative influences on CREB activity. These effects of estradiol were sex specific and traced to membrane-localized estrogen receptors that stimulated group I and II metabotropic glutamate receptor (mGluR) signaling. Activation of estrogen receptor α (ERα) led to mGluR1a signaling, triggering CREB phosphorylation through phospholipase C regulation of MAPK. In addition, estradiol stimulation of ERα or ERβ triggered mGluR2/3 signaling, decreasing L-type calcium channel-mediated CREB phosphorylation. These results not only characterize estradiol regulation of CREB but also provide two putative signaling mechanisms that may account for many of the unexplained observations regarding the influence of estradiol on nervous system function.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2005
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 2
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    American Physiological Society ; 2012
    In:  Journal of Neurophysiology Vol. 108, No. 4 ( 2012-08-15), p. 1186-1198
    In: Journal of Neurophysiology, American Physiological Society, Vol. 108, No. 4 ( 2012-08-15), p. 1186-1198
    Kurzfassung: Multiple classes of inhibitory interneurons shape the activity of principal neurons of the dorsal cochlear nucleus (DCN), a primary target of auditory nerve fibers in the mammalian brain stem. Feedforward inhibition mediated by glycinergic vertical cells (also termed tuberculoventral or corn cells) is thought to contribute importantly to the sound-evoked response properties of principal neurons, but the cellular and synaptic properties that determine how vertical cells function are unclear. We used transgenic mice in which glycinergic neurons express green fluorescent protein (GFP) to target vertical cells for whole cell patch-clamp recordings in acute slices of DCN. We found that vertical cells express diverse intrinsic spiking properties and could fire action potentials at high, sustained spiking rates. Using paired recordings, we directly examined synapses made by vertical cells onto fusiform cells, a primary DCN principal cell type. Vertical cell synapses produced unexpectedly small-amplitude unitary currents in fusiform cells, and additional experiments indicated that multiple vertical cells must be simultaneously active to inhibit fusiform cell spike output. Paired recordings also revealed that a major source of inhibition to vertical cells comes from other vertical cells.
    Materialart: Online-Ressource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 2012
    ZDB Id: 80161-6
    ZDB Id: 1467889-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 3
    In: Current Biology, Elsevier BV, Vol. 26, No. 15 ( 2016-08), p. 2070-2077
    Materialart: Online-Ressource
    ISSN: 0960-9822
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2016
    ZDB Id: 2019214-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 4
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    Elsevier BV ; 2009
    In:  Neuron Vol. 63, No. 5 ( 2009-09), p. 566-567
    In: Neuron, Elsevier BV, Vol. 63, No. 5 ( 2009-09), p. 566-567
    Materialart: Online-Ressource
    ISSN: 0896-6273
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2009
    ZDB Id: 2001944-0
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 5
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    Elsevier BV ; 2016
    In:  Neuron Vol. 90, No. 2 ( 2016-04), p. 320-332
    In: Neuron, Elsevier BV, Vol. 90, No. 2 ( 2016-04), p. 320-332
    Materialart: Online-Ressource
    ISSN: 0896-6273
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2016
    ZDB Id: 2001944-0
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 6
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    Elsevier BV ; 2011
    In:  Neuron Vol. 71, No. 2 ( 2011-07), p. 306-318
    In: Neuron, Elsevier BV, Vol. 71, No. 2 ( 2011-07), p. 306-318
    Materialart: Online-Ressource
    ISSN: 0896-6273
    Sprache: Englisch
    Verlag: Elsevier BV
    Publikationsdatum: 2011
    ZDB Id: 2001944-0
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 7
    Online-Ressource
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    Society for Neuroscience ; 2009
    In:  The Journal of Neuroscience Vol. 29, No. 30 ( 2009-07-29), p. 9625-9634
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 29, No. 30 ( 2009-07-29), p. 9625-9634
    Kurzfassung: Identification of shared features between avian and mammalian auditory brainstem circuits has provided much insight into the mechanisms underlying early auditory processing. However, previous studies have highlighted an apparent difference in inhibitory systems; synaptic inhibition is thought to be slow and GABAergic in birds but to have fast kinetics and be predominantly glycinergic in mammals. Using patch-clamp recordings in chick brainstem slices, we found that this distinction is not exclusively true. Consistent with previous work, IPSCs in nucleus magnocellularis (NM) were slow and mediated by GABA A receptors. However, IPSCs in nucleus laminaris (NL) and a subset of neurons in nucleus angularis (NA) had rapid time courses twofold to threefold faster than those in NM. Furthermore, we found that IPSCs in NA were mediated by both glycine and GABA A receptors, demonstrating for the first time a role for fast glycinergic transmission in the avian auditory brainstem. Although NM, NL, and NA have unique roles in auditory processing, the majority of inhibitory input to each nucleus arises from the same source, ipsilateral superior olivary nucleus (SON). Our results demonstrate remarkable diversity of inhibitory transmission among the avian brainstem nuclei and suggest that differential glycine and GABA A receptor activity tailors inhibition to the specific functional roles of NM, NL, and NA despite common SON input. We additionally observed that glycinergic/GABAergic activity in NA was usually depolarizing and could elicit spiking activity in NA neurons. Because NA projects to SON, these excitatory effects may influence the recruitment of inhibitory activity in the brainstem nuclei.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2009
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 8
    Online-Ressource
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    American Physiological Society ; 2009
    In:  Journal of Neurophysiology Vol. 102, No. 2 ( 2009-08), p. 1218-1226
    In: Journal of Neurophysiology, American Physiological Society, Vol. 102, No. 2 ( 2009-08), p. 1218-1226
    Kurzfassung: The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca 2+ . We examined Ca 2+ signaling through patch clamp and ion imaging experiments in slices containing nucleus laminaris from embryonic chicks. Voltage-clamp recordings of neurons located in the NL showed the presence of large Ca 2+ currents of two types, a low voltage–activated, fast inactivating Ni 2+ sensitive channel resembling mammalian T-type channels, and a high voltage–activated, slowly inactivating Cd 2+ sensitive channel. Two-photon Ca 2+ imaging showed that both channel types were concentrated on dendrites, even at their distal tips. Single action potentials triggered synaptically or by somatic current injection immediately elevated Ca 2+ throughout the entire cell. Ca 2+ signals triggered by subthreshold synaptic activity were highly localized. Thus when electrical activity is suprathreshold, Ca 2+ channels ensure that Ca 2+ rises in all dendrites, even those that are synaptically inactive.
    Materialart: Online-Ressource
    ISSN: 0022-3077 , 1522-1598
    RVK:
    Sprache: Englisch
    Verlag: American Physiological Society
    Publikationsdatum: 2009
    ZDB Id: 80161-6
    ZDB Id: 1467889-5
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 9
    Online-Ressource
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    Society for Neuroscience ; 2020
    In:  The Journal of Neuroscience Vol. 40, No. 41 ( 2020-10-07), p. 7785-7794
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 40, No. 41 ( 2020-10-07), p. 7785-7794
    Kurzfassung: The extracellular space (ECS) plays an important role in the physiology of neural circuits. Despite our detailed understanding of the cellular architecture of the mammalian retina, little is known about the organization and dynamics of the retinal ECS. We developed an optical technique based on two-photon imaging of fluorescently labeled extracellular fluid to measure the ECS volume fraction (α) in the ex vivo retina of male and female mice. This method has high spatial resolution and can detect rapid changes in α evoked by osmotic challenge and neuronal activity. The measured ECS α varied dramatically in different layers of the adult mouse retina, with α equaling ∼0.050 in the ganglion cell layer, ∼0.122 in the inner plexiform layer (IPL), ∼0.025 in the inner nuclear layer (INL), ∼0.087 in the outer plexiform layer, and ∼0.026 in the outer nuclear layer (ONL). ECS α was significantly larger early in retinal development; α was 67% larger in the IPL and 100% larger in the INL in neonatal mice compared with adults. In adult retinas, light stimulation evoked rapid decreases in ECS α. Light-driven reductions in ECS α were largest in the IPL, where visual stimuli decreased α values ∼10%. These light-evoked decreases demonstrate that a physiological stimulus can lead to rapid changes in ECS α and indicate that activity-dependent regulation of extracellular space may contribute to visual processing in the retina. SIGNIFICANCE STATEMENT The volume fraction of the extracellular space (ECS α), that portion of CNS tissue occupied by interstitial space, influences the diffusion of neurotransmitters from the synaptic cleft and the volume transmission of transmitters. However, ECS α has never been measured in live retina, and little is known about how ECS α varies following physiological stimulation. Here we show that ECS α values vary dramatically between different retinal layers and decrease by 10% following light stimulation. ECS α differences within the retina will influence volume transmission and light-evoked α variations may modulate synaptic transmission and visual processing in the retina. Activity-dependent ECS α variations may represent a mechanism of synaptic modulation throughout the CNS.
    Materialart: Online-Ressource
    ISSN: 0270-6474 , 1529-2401
    Sprache: Englisch
    Verlag: Society for Neuroscience
    Publikationsdatum: 2020
    ZDB Id: 1475274-8
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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  • 10
    Online-Ressource
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    Wiley ; 2022
    In:  Glia Vol. 70, No. 10 ( 2022-10), p. 1927-1937
    In: Glia, Wiley, Vol. 70, No. 10 ( 2022-10), p. 1927-1937
    Kurzfassung: Volume transmission plays an essential role in CNS function, with neurotransmitters released from synapses diffusing through the extracellular space (ECS) to distant sites. Changes in the ECS volume fraction ( α ) will influence the diffusion and the concentration of transmitters within the ECS. We have recently shown that neuronal activity evoked by physiological photic stimuli results in rapid decreases in ECS α as large as 10% in the retina. We now characterize the cellular mechanisms responsible for this ECS shrinkage. We find that block of inwardly rectifying K + channels with Ba 2+ , inhibition of the Na + /K + /2Cl − cotransporter with bumetanide, or block of AQP4 water channels with TGN‐020 do not diminish the light‐evoked ECS decrease. Inhibition of the Na + /HCO 3 − cotransporter by removing HCO 3 − from the superfusate, in contrast, reduces the light‐evoked ECS decrease by 95.6%. Inhibition of the monocarboxylate transporter with alpha‐cyano‐4‐hydroxycinnamate (4‐CIN) also reduces the ECS shrinkage, but only by 32.5%. We tested whether the swelling of Müller cells, the principal glial cells of the retina, is responsible for the light‐evoked ECS shrinkage. Light stimulation evoked a 6.3% increase in the volume of the fine processes of Müller cells. This volume increase was reduced by 97.1% when HCO 3 − was removed from the superfusate. We conclude that a large fraction of the activity‐dependent decrease in ECS α is generated by the activation of the Na + /HCO 3 − cotransporter in Müller cells. The monocarboxylate transporter may also contribute to the response.
    Materialart: Online-Ressource
    ISSN: 0894-1491 , 1098-1136
    URL: Issue
    Sprache: Englisch
    Verlag: Wiley
    Publikationsdatum: 2022
    ZDB Id: 1474828-9
    SSG: 12
    Standort Signatur Einschränkungen Verfügbarkeit
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