Localization of heterotypic gap junctions composed of connexin45 and connexin36 in the rod pathway of the mouse retina
ABSTRACT The primary rod pathway in mammals contains gap junctions between AII amacrine cells and ON cone bipolar cells which relay the rod signal into the cone pathway under scotopic conditions. Two gap junctional proteins, connexin36 (Cx36) and connexin45 (Cx45), appear to play a pivotal role in this pathway because lack of either protein leads to an impairment of visual transmission under scotopic conditions. To investigate whether these connexins form heterotypic gap junctions between ON cone bipolar and AII amacrine cells, we used newly developed Cx45 antibodies and studied the cellular and subcellular distribution of this protein in the mouse retina. Specificity of the Cx45 antibodies was determined, among others, by Western blot and immunostaining of mouse heart, where Cx45 is abundantly expressed. In mouse retina, Cx45 immunosignals were detected in both plexiform layers and the ganglion cell layer. Double staining for Cx45 and Cx36 revealed a partial overlap in the punctate patterns in the ON sublamina of the inner plexiform layer of the retina. We quantified the distributions of these two connexins in the ON sublamina, and detected 30% of the Cx45 signals to be co-localized with or in close apposition to Cx36 signals. Combining immunostaining and intracellular dye injection revealed an overlap or tight association of Cx36 and Cx45 signals on the terminals of injected AII amacrine and two types of ON cone bipolar cells. Our results provide direct evidence for heterotypic gap junctions composed of Cx36 and Cx45 between AII amacrine and certain types of ON cone bipolar cells.
- SourceAvailable from: Bela Volgyi
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- "e connexon embedded in AII cell plasma membrane ( Feigenspan et al . , 2001 ; Güldenagel et al . , 2001 ; Mills et al . , 2001 ; Deans et al . , 2002 ) . There has been a debate , however , over the connexin subunit that forms ON cone bipolar cell connexons . While most studies detected Cx45 in bipolar cell hemichannels ( Maxeiner et al . , 2005 ; Dedek et al . , 2006 ; Hilgen et al . , 2011 ) , there is evidence for the presence of Cx36 as well ( Han and Massey , 2005 ) . This apparent inconsistency seems resolved by the finding that either Cx36 or Cx45 could contribute to ON bipolar cell connexons in a bi - polar cell type specific manner ( Lin et al . , 2005 ) . This implies that some of these cont"
ABSTRACT: Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such as signal averaging and synchronization.Progress in Retinal and Eye Research 01/2013; 34. DOI:10.1016/j.preteyeres.2012.12.002 · 9.90 Impact Factor
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- "Initial studies suggested that DA does not modulate AII–ON cone bipolar tracer coupling (Mills & Massey, 1995), which appears to be mediated by heteromeric Cx36/Cx45 gap junctions (Han & Massey, 2005; Maxeiner et al., 2005; Dedek et al., 2006 "
ABSTRACT: Amacrine cells represent the most diverse class of retinal neuron, comprising dozens of distinct cell types. Each type exhibits a unique morphology and generates specific visual computations through its synapses with a subset of excitatory interneurons (bipolar cells), other amacrine cells, and output neurons (ganglion cells). Here, we review the intrinsic and network properties that underlie the function of the most common amacrine cell in the mammalian retina, the AII amacrine cell. The AII connects rod and cone photoreceptor pathways, forming an essential link in the circuit for rod-mediated (scotopic) vision. As such, the AII has become known as the rod-amacrine cell. We, however, now understand that AII function extends to cone-mediated (photopic) vision, and AII function in scotopic and photopic conditions utilizes the same underlying circuit: AIIs are electrically coupled to each other and to the terminals of some types of ON cone bipolar cells. The direction of signal flow, however, varies with illumination. Under photopic conditions, the AII network constitutes a crossover inhibition pathway that allows ON signals to inhibit OFF ganglion cells and contributes to motion sensitivity in certain ganglion cell types. We discuss how the AII's combination of intrinsic and network properties accounts for its unique role in visual processing.Visual Neuroscience 01/2012; 29(1):51-60. DOI:10.1017/S0952523811000368 · 1.68 Impact Factor
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- "In adult retinas, Cx45 is expressed in bipolar cells (BCs), where it forms a part of the gap junction between AII amacrine cells and cone BCs (Han and Massey, 2005; Lin et al., 2005; Maxeiner et al., 2005; Dedek et al., 2006). It is also expressed in amacrine cells (Maxeiner et al., 2005; Dedek et al., 2006) and RGCs (Schubert et al., 2005a; for review, see Bloomfield and Völgyi, 2009). Cx45 antibodies produce strong labeling of mouse retinas from P1 to adulthood, and Cx45 mRNA levels are high at P1 and slowly decrease until adulthood (Kihara et al., 2006), similar to connexins that are transiently expressed in developing spinal cord (Chang et al., 1999). "
ABSTRACT: Gap junction coupling synchronizes activity among neurons in adult neural circuits, but its role in coordinating activity during development is less known. The developing retina exhibits retinal waves--spontaneous depolarizations that propagate among retinal interneurons and drive retinal ganglion cells (RGCs) to fire correlated bursts of action potentials. During development, two connexin isoforms, connexin 36 (Cx36) and Cx45, are expressed in bipolar cells and RGCs, and therefore provide a potential substrate for coordinating network activity. To determine whether gap junctions contribute to retinal waves, we compared spontaneous activity patterns using calcium imaging, whole-cell recording, and multielectrode array recording in control, single-knock-out (ko) mice lacking Cx45 and double-knock-out (dko) mice lacking both isoforms. Wave frequency, propagation speed, and bias in propagation direction were similar in control, Cx36ko, Cx45ko, and Cx36/45dko retinas. However, the spontaneous firing rate of individual retinal ganglion cells was elevated in Cx45ko retinas, similar to Cx36ko retinas (Hansen et al., 2005; Torborg and Feller, 2005), a phenotype that was more pronounced in Cx36/45dko retinas. As a result, spatial correlations, as assayed by nearest-neighbor correlation and functional connectivity maps, were significantly altered. In addition, Cx36/45dko mice had reduced eye-specific segregation of retinogeniculate afferents. Together, these findings suggest that although Cx36 and Cx45 do not play a role in gross spatial and temporal propagation properties of retinal waves, they strongly modulate the firing pattern of individual RGCs, ensuring strongly correlated firing between nearby RGCs and normal patterning of retinogeniculate projections.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 07/2011; 31(27):9998-10008. DOI:10.1523/JNEUROSCI.5640-10.2011 · 6.75 Impact Factor