Nonsynaptic NMDA Receptors Mediate Activity-Dependent Plasticity of Gap Junctional Coupling in the AII Amacrine Cell Network

Kothmann, W. Wade; Trexler, E. Brady; Whitaker, Christopher J.; Li, Wei; Massey, Stephen C.; O’Brien, John

doi:10.1523/jneurosci.5087-11.2012

Cited by 79 publications

(112 citation statements)

References 67 publications

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“…Varying the strength of presynaptic activation leads to differential activation of the different types of postsynaptic AMPA receptors, depending on the degree of spillout of glutamate at these synapses. If similar mechanisms are operative at the bipolar cell inputs to AII amacrines, changes in the Ca 2ϩ permeability of AMPA receptors evoked by diabetes could influence the signaling and integrative properties of AII amacrine cells, including the activity-driven intracellular Ca 2ϩ dynamics related to regulating the strength of gap junction-mediated electrical coupling between AII amacrine cells (Kothmann et al 2009(Kothmann et al , 2012 which is likely to be an important mechanism for postreceptoral visual adaptation (reviewed by Demb 2010).…”

Section: Discussionmentioning

confidence: 99%

Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Castilho

Madsen

Ambrósio

et al. 2015

Journal of Neurophysiology

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Castilho Á, Madsen E, Ambrósio AF, Veruki ML, Hartveit E. Diabetic hyperglycemia reduces Ca 2ϩ permeability of extrasynaptic AMPA receptors in AII amacrine cells. J Neurophysiol 114: 1545-1553, 2015. First published July 8, 2015 doi:10.1152/jn.00295.2015.-There is increasing evidence that diabetic retinopathy is a primary neuropathological disorder that precedes the microvascular pathology associated with later stages of the disease. Recently, we found evidence for altered functional properties of synaptic ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in A17, but not AII, amacrine cells in the mammalian retina, and the observed changes were consistent with an upregulation of the GluA2 subunit, a key determinant of functional properties of AMPA receptors, including Ca 2ϩ permeability and current-voltage (I-V) rectification properties. Here, we have investigated functional changes of extrasynaptic AMPA receptors in AII amacrine cells evoked by diabetes. With patch-clamp recording of nucleated patches from retinal slices, we measured Ca 2ϩ permeability and I-V rectification in rats with ϳ3 wk of streptozotocin-induced diabetes and age-matched, noninjected controls. Under bi-ionic conditions (extracellular Ca 2ϩ concentration ϭ 30 mM, intracellular Cs ϩ concentration ϭ 171 mM), the reversal potential (E rev ) of AMPA-evoked currents indicated a significant reduction of Ca 2ϩ permeability in diabetic animals [E rev ϭ Ϫ17.7 mV, relative permeability of Ca 2ϩ compared with Cs ϩ (P Ca /P Cs ) ϭ 1.39] compared with normal animals (E rev ϭ Ϫ7.7 mV, P Ca /P Cs ϭ 2.35). Insulin treatment prevented the reduction of Ca 2ϩ permeability. I-V rectification was examined by calculating a rectification index (RI) as the ratio of the AMPA-evoked conductance at ϩ40 and Ϫ60 mV. The degree of inward rectification in patches from diabetic animals (RI ϭ 0.48) was significantly reduced compared with that in normal animals (RI ϭ 0.30). These results suggest that diabetes evokes a change in the functional properties of extrasynaptic AMPA receptors of AII amacrine cells. These changes could be representative for extrasynaptic AMPA receptors elsewhere in AII amacrine cells and suggest that synaptic and extrasynaptic AMPA receptors are differentially regulated.

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Section: Discussionmentioning

confidence: 99%

Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Castilho

Madsen

Ambrósio

et al. 2015

Journal of Neurophysiology

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“…Although there has been no direct observation of activity-dependent modifications of gap-junction between RGCs, some studies suggested that gap-junction strength could be modulated by dopamine, the activity of which is influenced by the luminance of the environment (Bloomfield and Volgyi 2009). Also, luminance-and activity-dependent modifications of gap-junctions between amacrine cells have been found in the retina (Bloomfield et al 1997;Kothmann et al 2012). Alternatively, there may exist other mechanisms which could generate the observed enhanced synchrony behavior.…”

Section: Discussionmentioning

confidence: 99%

Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation

Xiao

Zhang

Xing

et al. 2013

Journal of Neurophysiology

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Neuronal responses to prolonged stimulation attenuate over time. Here, we ask a fundamental question: is adaptation a simple process for the neural system during which sustained input is ignored, or is it actually part of a strategy for the neural system to adjust its encoding properties dynamically? After simultaneously recording the activities of a group of bullfrog's retinal ganglion cells (dimming detectors) in response to sustained dimming stimulation, we applied a combination of information analysis approaches to explore the time-dependent nature of information encoding during the adaptation. We found that at the early stage of the adaptation, the stimulus information was mainly encoded in firing rates, whereas at the late stage of the adaptation, it was more encoded in neural correlations. Such a transition in encoding properties is not a simple consequence of the attenuation of neuronal firing rates, but rather involves an active change in the neural correlation strengths, suggesting that it is a strategy adopted by the neural system for functional purposes. Our results reveal that in encoding a prolonged stimulation, the neural system may utilize concerted, but less active, firings of neurons to encode information.retinal ganglion cell; luminance adaptation; information coding; neural correlation; discrimination ADAPTATION REFERS TO A GENERAL phenomenon in which a neural system adjusts its response property according to the statistics of external inputs (Kohn 2007;Wark et al. 2007). It has been widely suggested that adaptation underlies the strategy for a neural system to utilize its resource efficiently to encode stimulus information (Fairhall et al. 2001;Gutnisky and Dragoi 2008;Lesica et al. 2007;Maravall et al. 2007). For instance, it was found that the tuning functions of sensory neurons are optimized to match the variance of inputs in a natural environment, so that high encoding accuracy for the whole range of stimuli is achieved (Laughlin 1981). In practice, adaptation can also occur very rapidly in response to sudden changes in the input statistics, so that the stimulus information is transmitted with high fidelity (Fairhall et al. 2001;Sharpee et al. 2006). A recent experimental work reported that in addition to enhancing information representation, adaptation can regulate information content transmitted in the sensory pathway (Wang et al. 2010). Thus, to fully understand how the brain processes stimulus information in a natural dynamical environment, it is critical to unveil the computational roles associated with adaptation.Luminance adaptation, in which a neural system is exposed to a sustained stimulation with constant luminance, is a fundamental visual adaptation process whose biophysical mechanisms and potential computational roles have been intensively studied (Wark et al. 2007). However, the detailed time course as to how the stimulus information is encoded dynamically in the varying neural responses during adaptation remains largely unresolved (Kastner and Baccus 2011). In luminance ad...

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“…The AII amacrine cell is characteristically poorly coupled in prolonged, complete darkness, but develops extensive coupling with dim background light [9]. Kothmann et al [••29] found that this light-dependent enhancement in coupling is driven by glutamate spillover from On bipolar cell (either rod- or cone-driven) activity. Enhancement of coupling depends on activation of non-synaptic NMDA receptors, activation of CaM Kinase II, and phosphorylation of Cx36.…”

Section: Seeing All Of the Lightmentioning

confidence: 99%

“…This effect required activation of CaMKII and was limited to weakly coupled IO neurons. Turecek et al [••10] further found that non-synaptic NMDA receptors were closely associated with Cx36 gap junctions in the IO glomeruli, implicating a signaling pathway highly analogous to that of retinal AII amacrine cells [••29]. NMDA application induced synchrony and enhanced the amplitudes of subthreshold oscillations, revealing a mechanism by which excitatory input can enhance the synchrony of the IO network [••10].…”

Section: Timing Is Everythingmentioning

confidence: 99%

The ever-changing electrical synapse

O’Brien

2014

Current Opinion in Neurobiology

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A wealth of research has revealed that electrical synapses in the central nervous system exhibit a high degree of plasticity. Several recent studies, particularly in the retina and inferior olive, highlight this plasticity. Three classes of mechanisms can alter electrical coupling over time courses ranging from milliseconds to days. Changes of membrane conductance through synaptic input or spiking activity shunt current and decouple neurons on the millisecond time scale. Such activity can also alter coupling symmetry, rectifying electrical synapses. More stable rectification can be accomplished through molecular asymmetry of the synapse itself. On the minutes time scale, changes in connexin phosphorylation can change coupling quasi-stably with order of magnitude dynamic range. On the hours to days time scale, changes in expression level of connexins alter coupling through the course of circadian time, over developmental time, or in response to tissue injury. Combined, all of these mechanisms allow electrical coupling to be highly dynamic, changing in response to demands at the whole network level, in small portions of a network, or at the level of an individual synapse.

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Nonsynaptic NMDA Receptors Mediate Activity-Dependent Plasticity of Gap Junctional Coupling in the AII Amacrine Cell Network

Cited by 79 publications

References 67 publications

Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation

The ever-changing electrical synapse

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Nonsynaptic NMDA Receptors Mediate Activity-Dependent Plasticity of Gap Junctional Coupling in the AII Amacrine Cell Network

Cited by 79 publications

References 67 publications

Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Diabetic hyperglycemia reduces Ca2+ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Shifted encoding strategy in retinal luminance adaptation: from firing rate to neural correlation

The ever-changing electrical synapse

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Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells

Diabetic hyperglycemia reduces Ca²⁺ permeability of extrasynaptic AMPA receptors in AII amacrine cells