Because the mouse retina has become an important model system, we have begun to identify its specific neuron types and their synaptic connections. Here, based on electron micrographs of serial sections, we report that the wild-type mouse retina expresses the standard rod pathways known in other mammals: (1) rod --> cone (via gap junctions) to inject rod signals into the cone bipolar circuit; and (2) rod --> rod bipolar --> AII amacrine --> cone bipolar --> ganglion cell. The mouse also expresses another rod circuit: a bipolar cell with cone input also receives rod input at symmetrical contacts that express ionotropic glutamate receptors (Hack et al., 1999, 2001). We show that this rod-cone bipolar cell sends an axon to the outer (OFF) strata of the inner plexiform layer to form ribbon synapses with ganglion and amacrine cells. This rod-cone bipolar cell receives direct contacts from only 20% of all rod terminals. However, we also found that rod terminals form gap junctions with each other and thus establish partial syncytia that could pool rod signals for direct chemical transmission to the OFF bipolar cell. This third rod pathway probably explains the rod responses that persist in OFF ganglion cells after the well known rod pathways are blocked (Soucy et al., 1998).

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The rod bipolar cell and about five types of ON cone bipolar cells depolarize to light by employing a sign-reversing metabotropic glutamate receptor. Glutamate responses are similar in both rod bipolar and cone bipolar cells, but the receptor mediating this response (mGluRo) was so far demonstrated only in rod bipolar cells. To test if ON cone bipolar cells also express mGluR6, we immunoreacted rat retina with an antibody specific for mGluRo, and studied the staining from serial ultrathin sections. We demonstrate that mGluR6 is indeed expressed in the dendritic tips of cone bipolar cells, the majority of which receive a ribbon synapse, and thus probably are ON cone bipolar cells. We further show that half of the dendritic tips contacting the cones stain for mGluR6, thus implying that all ON cone bipolar cell types express mGluR6.

The nasotemporal overlap of crossed and uncrossed retinal ganglion cell projections were studied in 11 Japanese monkeys (Macaca fuscata) using HRP and fluorescent dyes (DAPI and RITC) as retrograde tracers and by physiological recordings of antidromic field potentials. A strip of nasotemporal overlap ran orthogonal to the horizontal meridian in all the whole-mount retinas studied. In HRP-labeled retinas of 6 monkeys, the width of the overlap gradually increased from 0.6 degrees in the central retina up to 5 degrees at eccentricity of 5 mm, and to 15 degrees at the extreme periphery. We also noted a clear asymmetric distribution of crossed and uncrossed retinal ganglion cell projections particularly in the perifoveal region; ipsilaterally projecting cells encircled the nasal edge of the fovea, whereas few contralaterally projecting cells were observed in the temporal edge. Soma-size analysis revealed that crossed projections in the temporal portion of the overlap arose mainly from large and small cells (presumably P alpha and P gamma cells, respectively); uncrossed projections in its nasal portion arose from medium-sized cells (presumably P beta cell). Direct evidence of the overlap as well as of the asymmetry was obtained in subsequent fluorescent dye experiments in 3 monkeys. Physiological studies on 2 additional monkeys confirmed the widening of the nasotemporal overlap towards the upper and lower parts of the retina. Moreover, in the nasal portion of the overlap, only slow potentials, which presumably reflect activities of P beta cells, were recorded after stimulation of the ipsilateral LGN as expected from the morphological study. The findings are discussed in relation to clinical observations of macular sparing and splitting, and with regard to the functional differences between P alpha and P beta cell systems on which binocular stereoscopic vision along the midsagittal plane may be based.

(i) mGluR6 receptors concentrate on dendrites at the base of the invagination rather than at the apex. This implies that receptors at both 'invaginating' and 'basal' contacts lie roughly equidistant from the release sites and should therefore receive similar spatiotemporal concentrations of glutamate. (ii) The 'cone' membrane is electron-dense opposite to the receptor sites on both ON and OFF bipolar cells. This suggests a special role for this region in synaptic transmission. Possibly, these densities signify a transporter that would regulate glutamate concentration at sites remote (> 200 nm) from the locus of vesicle release.

Since the discovery of direct chemical synapses between rod photoreceptor and OFF cone bipolar cells in mouse retinas, whether the ON cone bipolar cell also receive direct chemical input from rod has been a pending question. In finding that metabotropic glutamate receptor 7 (mGluR7) was uniquely expressed in dendrites of ON cone bipolar cells in the mGluR6-deficient mouse retina, we used this ectopic mGluR7 immunoreactivity as a specific marker for the ON cone bipolar to search for its rod connection. Here, we show that a certain type of ON cone bipolar cell forms ribbon-associated synapses not only with cones, but also rods. This finding was verified in the wild-type mouse retina by three-dimensional reconstruction of bipolar cells from serial electron micrographs. These ON cone bipolars were further identified as corresponding to type 7 of mouse bipolar cell described by Ghosh et al.

The somato-dendritic morphologies of large ganglion cells were studied by intracellular injections of Lucifer yellow in perfused in vitro preparations of the albino rat retina. The ganglion cells were prelabeled with retrogradely transported granular blue or labeled with acridine orange dropped into the perfusate of in vitro preparations. After the dye injection, somato-dendritic morphologies were successfully studied for 210 cells, the majority of which had a large soma more than 20 microns in diameter and were identified as alpha cells. According to the level of dendritic extensions within the inner plexiform layer (IPL) these alpha cells were further classified into inner ramifying (inner) and outer ramifying (outer) cells. Both qualitative and quantitative observations led us to conclude the following: 1) The outer cells have a spherical soma with relatively few primary dendrites, while inner cells have a large polygonal soma with more primary dendrites. 2) The dendritic field of inner cells was always larger than that of outer cells at every retinal location. The dendritic field diameter tended to increase as a function of retinal eccentricity from the optic disk, the tendency being more clear among inner cells. 3) The dendrites of outer cells branch more frequently in the proximal part of the dendritic field while those of inner cells branch more distally. 4) Total dendritic length of outer cells increases linearly with eccentricity whereas that of the inner cells does not change much irrespective of retinal location.

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