BLOCKADE OF GLUTAMATE-MEDIATED ACTIVITY IN THE DEVELOPING RETINA PERTURBS THE FUNCTIONAL SEGREGATION OF ON AND OFF PATHWAYS

The dendrites of ganglion cells initially ramify throughout the inner plexiform layer of the developing retina before becoming stratified in to ON or OFF sublaminae. This ontogenetic event is thought to depend o n glutamate-mediated afferent activity, because treating the developin g retina with the glutamate analog 2-amino-4-phosphonobutyrate (APE), which hyperpolarizes ON cone bipolar cells and rod bipolar cells, ther eby preventing their release of glutamate, effectively arrests the den dritic stratification process. To assess the functional consequences o f this manipulation, extracellular recordings were made from single ce lls in the A laminae of the dorsal lateral geniculate nucleus and from the optic tract in mature cats that had received intraocular injectio ns of APE during the first postnatal month. Such recordings revealed t hat stimulation of the APE-treated eye evoked both ON as well as OFF d ischarges in 37% of the cells tested. (As expected, when the normal ey e was activated, virtually all cells yielded only ON or OFF responses. ) The proportion of ON-OFF cells found here corresponds closely to the incidence of multistratified dendrites observed previously in anatomi cal studies of APE-treated cat retinas. This suggests that the ganglio n cells with multistratified dendrites receive functional inputs from ON as well as OFF cone bipolar cells. This interpretation is further s upported by the finding that the proportion of ON-OFF cells was very s imilar in the geniculate layer innervated by the treated eye and in th e optic tract. The cells activated by the APE-treated eye were also fo und not to show response suppression when flashing stimuli of increasi ng size were used. This suggests that exposing the developing retina t o APE perturbs the neural circuitry mediating the antagonistic center- surround organization found in normal receptive fields. The functional changes evident after treating the developing retina with APE suggest that it should now be feasible to assess how the segregation of ON an d OFF retinal pathways relates to organizational features at higher le vels of the visual system, such as orientation selectivity in cortical cells.