Connexin36 Expression in the Mammalian Retina: A Multiple-Species Comparison

Abstract

Much knowledge about interconnection of human retinal neurons is inferred from results on animal models. Likewise, there is a lack of information on human retinal electrical synapses/gap junctions (GJ). Connexin36 (Cx36) forms GJs in both the inner and outer plexiform layers (IPL and OPL) in most species including humans. However, a comparison of Cx36 GJ distribution in retinas of humans and popular animal models has not been presented. To this end a multiple-species comparison was performed in retinas of 12 mammals including humans to survey the Cx36 distribution. Areas of retinal specializations were avoided (e.g., fovea, visual streak, area centralis), thus observed Cx36 distribution differences were not attributed to these species-specific architecture of central retinal areas. Cx36 was expressed in both synaptic layers in all examined retinas. Cx36 plaques displayed an inhomogenous IPL distribution favoring the ON sublamina, however, this feature was more pronounced in the human, swine and guinea pig while it was less obvious in the rabbit, squirrel monkey, and ferret retinas. In contrast to the relative conservative Cx36 distribution in the IPL, the labels in the OPL varied considerably among mammals. In general, OPL plaques were rare and rather small in rod dominant carnivores and rodents, whereas the human and the cone rich guinea pig retinas displayed robust Cx36 labels. This survey presented that the human retina displayed two characteristic features, a pronounced ON dominance of Cx36 plaques in the IPL and prevalent Cx36 plaque conglomerates in the OPL. While many species showed either of these features, only the guinea pig retina shared both. The observed similarities and subtle differences in Cx36 plaque distribution across mammals do not correspond to evolutionary distances but may reflect accomodation to lifestyles of examined species.

Spatial Expression Pattern of the Major Ca2+-buffer Proteins in the Mouse Retinal Ganglion Cells

“…Soma sizes often show a strong correlation to the diameters of corresponding dendritic fields, therefore it is likely that PV-IR RGC subtypes with smaller dendritic fields in the morphological analyses correspond to cells of small somata of this study, and cells with larger cell bodies maintain larger dendritic arbors as well. In fact, morphological analyses differentiated 2-3 large-field (PV1, PV5, PV6 [5]; PV7, PV8 [17]) and 5-6 small/medium-sized (PV2, PV3, PV4, PV7 [5]; PV3, PV4, PV5, PV6 [18]) PV expressing RGC populations. Moreover, these RGC populations corresponded well to our cluster analyses in the Dp/Tp areas, where we found 1-2 clusters of RGCs with large somata and more than 5 clusters with small-medium sized cell bodies.…”

“…Therefore, none of them can be utilized effectively as a subtype-specific RGC marker in retinal morphology studies. However, CaBP labels proved useful for labeling retinal layers [18], or combined with other markers, served as a methodological approach to selectively examine a subset of the RGC population. One such combined approach was presented in a series of studies by the Jeon laboratory.…”

Spatial Expression Pattern of the Major Ca2+-Buffer Proteins in Mouse Retinal Ganglion Cells

“…Soma sizes often show a strong correlation to the diameters of corresponding dendritic fields, therefore it is likely that PV-IR RGC subtypes with smaller dendritic fields in the morphological analyses correspond to cells of small somata of this study, and cells with larger cell bodies maintain larger dendritic arbors as well. In fact, morphological analyses differentiated to three large-field (PV1, PV5, PV6 [9]; PV7, PV8 [26]) and five to six small/medium-sized (PV2, PV3, PV4, PV7 [9]; PV3, PV4, PV5, PV6 [27]) PV expressing RGC populations. Moreover, these RGC populations corresponded well to our cluster analyses in the Dp/Tp areas, where we found one to two clusters of RGCs with large somata and more than five clusters with small/medium-sized cell bodies.…”

“…Therefore, none of them can be utilized effectively as a subtype-specific RGC marker in retinal morphology studies. However, CaBP labels have proved useful for labeling retinal layers [27] or, combined with other markers, served as a methodological approach to selectively examine a subset of the RGC population. One such combined approach was presented in a series of studies by the Jeon laboratory.…”

Effects of constitutive and acute Connexin 36 deficiency on brain-wide susceptibility to PTZ-induced neuronal hyperactivity

“…Connexin 36 (Cx36) is the main connexin expressed by neurons. It is involved in brain functions that rely on synchronous firing such as learning and memory (Allen, Fuchs, Jaschonek, Bannerman, & Monyer, 2011;Wang & Belousov, 2011), retina visual processing (Kovács-Öller et al, 2017), and sensorimotor reflex in the zebrafish (Miller et al, 2017). As the key structural component of electrical synapses, Cx36 may also act as a therapeutic target in diseases involving deficiencies in fast communication and aberrant synchronous firing, such as seizures.…”