Abstract
BackgroundRetinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. In this study, we have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo.ResultsUsing retroviral lineage analysis with the histochemical marker alkaline phosphatase, the percentage of cone and rod bipolar cells born on postnatal day 0 (P0), P4, and P6 were determined, based upon the well characterized morphology of these cells in the adult rat retina. In this in vivo experiment, we have demonstrated that cone bipolar genesis clearly precedes rod bipolar genesis. In addition, in the postnatal mouse retina, using a combination of tritiated-thymidine birthdating and immunohistochemistry to distinguish bipolar types, we have similarly found that cone bipolar genesis precedes rod bipolar genesis. The tritiated-thymidine birthdating studies also included quantification of the birth of all postnatally generated retinal cell types in the mouse.ConclusionUsing two independent in vivo methodologies in rat and mouse retina, we have demonstrated that there are distinct waves of genesis of the two major bipolar cell types, with cone bipolar genesis preceding rod bipolar genesis. These waves of bipolar genesis correspond to the order of genesis of the presynaptic photoreceptor cell types.
Highlights
Retinal bipolar cells comprise a diverse group of neurons
We directly demonstrate that there is a clear temporal relationship to bipolar type genesis, with birth of cone bipolar cells distinctly preceding that of rod bipolar cells both in both mouse and rat
Since the cell cycle is approximately 24 hours at postnatal day 0 (P0) [13,14], one can estimate that one cell clones and two cell clones comprise cells born on P1-P2 if the virus was delivered on P0
Summary
Retinal bipolar cells comprise a diverse group of neurons. Cone bipolar cells and rod bipolar cells are so named for their connections with cone and rod photoreceptors, respectively. Morphological criteria have been established that distinguish nine types of cone bipolar cells and one type of rod bipolar cell in mouse and rat. While anatomical and physiological aspects of bipolar types have been actively studied, little is known about the sequence of events that leads to bipolar cell type specification and the potential relationship this process may have with synapse formation in the outer plexiform layer. We have examined the birth order of rod and cone bipolar cells in the developing mouse and rat in vivo. The outer plexiform layer (OPL) contains the tripartite ribbon synapses of presynaptic horizontal and photoreceptor cells and the post-synaptic bipolar cells. Given the well characterized cellular morphology and biochemistry of the retina, the developmental processes of neurogenesis, cell fate determination, neuronal and glial differentiation have been actively studied. Bipolar cell type specification and its potential relationship with synaptogenesis have been relatively less well examined [5,6]
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