Abstract
Abstract: :
Introduction: Horizontal cells are coupled to each other by gap junctions, forming an extensive network that feeds back onto the photoreceptors. Because of this electrical coupling, the receptive field of each cell is considerably larger than its dendritic arbor. The large receptive fields of the horizontal cells are thought to mediate the antagonistic ‘center–surround’ properties exhibited by the bipolar and ganglion cells. Horizontal cell coupling has been shown to be mediated by Connexin57 (Cx57). Hombach and colleagues (2004) generated a mouse line in which the Cx57 coding region was replaced by a lacZ reporter gene expressed under the control of the endogenous Cx57 promoter. This mouse line demonstrated that Cx57 is expressed exclusively by horizontal cells in the mouse retina. Additionally, it was shown that tracer coupling is significantly reduced in Cx57–deficient mice, suggesting that Cx57 is involved in horizontal cell coupling. Purpose: In this study, we compare the receptive field sizes of horizontal cells from wildtype and Cx57–deficient mice to confirm the role of Cx57 in electrical coupling of the horizontal cell network. Methods: We have developed a method for recording from horizontal cells in the mouse retina using the inverted eyecup preparation. For quantitative evaluation, the receptive field can be described by the length constant = √(Rm/Rs), which can be derived from the cell’s responses to concentric spots of light of varying diameter. However, in the mouse, the receptive field size could not be described by a single length constant, because the length constant varied with stimulus intensity: increasing stimulus intensity caused a decrease in the length constant. Results: Horizontal cells from Cx57–deficient mice demonstrated smaller receptive fields than those from wildtype mice: the length constant at 50% of saturation was reduced from 103.5 µm in wildtype mice (n=26) to 81.1 µm (n=5) in knockout animals. As in the wildtype, the length constants of Cx57–deficient horizontal cells decreased with an increase in stimulus intensity. In addition, Cx57–deficient horizontal cells demonstrated an altered light sensitivity profile. The intensity that evoked half–maximal responses was reduced from –2.3 log units in the wildtype to –2.9 log units in knockout mice. Conclusions: Cx57 plays a key role in horizontal cell coupling: deletion of the Cx57 coding region results in elimination of dye coupling and a reduction in receptive field size. The Cx57–lacZ mouse line will therefore be a valuable tool for investigating the functional role of horizontal cell coupling in retinal processing.
Keywords: gap junctions/coupling • horizontal cells • receptive fields