The Role of Neuronal Connexins 36 and 45 in Shaping Spontaneous Firing Patterns in the Developing Retina
Male
Mice, Knockout
Neurons
0301 basic medicine
Gap Junction delta-2 Protein
Patch-Clamp Techniques
Green Fluorescent Proteins
Action Potentials
Nerve Tissue Proteins
Connexins
Retina
Choline O-Acetyltransferase
Mice
03 medical and health sciences
Animals, Newborn
Animals
Calcium
Female
Visual Pathways
RNA, Messenger
DOI:
10.1523/jneurosci.5640-10.2011
Publication Date:
2011-07-07T05:46:01Z
AUTHORS (7)
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.
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