Bisti S, Gargini C, Chalupa L M
Institute of Neurophysiology, Consiglio Nazionale delle Ricerche, Pisa 56127, Italy.
J Neurosci. 1998 Jul 1;18(13):5019-25. doi: 10.1523/JNEUROSCI.18-13-05019.1998.
The dendrites of ganglion cells initially ramify throughout the inner plexiform layer of the developing retina before becoming stratified into ON or OFF sublaminae. This ontogenetic event is thought to depend on glutamate-mediated afferent activity, because treating the developing retina with the glutamate analog 2-amino-4-phosphonobutyrate (APB), which hyperpolarizes ON cone bipolar cells and rod bipolar cells, thereby preventing their release of glutamate, effectively arrests the dendritic stratification process. To assess the functional consequences of this manipulation, extracellular recordings were made from single cells in the A laminae of the dorsal lateral geniculate nucleus and from the optic tract in mature cats that had received intraocular injections of APB during the first postnatal month. Such recordings revealed that stimulation of the APB-treated eye evoked both ON as well as OFF discharges in 37% of the cells tested. (As expected, when the normal eye 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 anatomical studies of APB-treated cat retinas. This suggests that the ganglion cells with multistratified dendrites receive functional inputs from ON as well as OFF cone bipolar cells. This interpretation is further supported by the finding that the proportion of ON-OFF cells was very similar in the geniculate layer innervated by the treated eye and in the optic tract. The cells activated by the APB-treated eye were also found not to show response suppression when flashing stimuli of increasing size were used. This suggests that exposing the developing retina to APB 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 APB suggest that it should now be feasible to assess how the segregation of ON and OFF retinal pathways relates to organizational features at higher levels of the visual system, such as orientation selectivity in cortical cells.
神经节细胞的树突最初在发育中的视网膜内网状层中广泛分支，然后才分层进入ON或OFF亚层。这种个体发育事件被认为依赖于谷氨酸介导的传入活动，因为用谷氨酸类似物2-氨基-4-膦酰丁酸（APB）处理发育中的视网膜，会使ON型视锥双极细胞和视杆双极细胞超极化，从而阻止它们释放谷氨酸，这有效地阻止了树突分层过程。为了评估这种操作的功能后果，在出生后第一个月接受眼内注射APB的成年猫的背外侧膝状核A层的单细胞和视束进行了细胞外记录。这样的记录显示，在37%的测试细胞中，刺激经APB处理的眼睛会诱发ON和OFF放电。（正如预期的那样，当正常眼睛被激活时，几乎所有细胞只产生ON或OFF反应。）这里发现的ON-OFF细胞的比例与先前在APB处理的猫视网膜的解剖学研究中观察到的多层树突的发生率密切对应。这表明具有多层树突的神经节细胞从ON型和OFF型视锥双极细胞接收功能性输入。这一解释得到了进一步支持，即经处理的眼睛支配的膝状层和视束中ON-OFF细胞的比例非常相似。还发现，经APB处理的眼睛激活的细胞在使用尺寸不断增加的闪烁刺激时不会表现出反应抑制。这表明将发育中的视网膜暴露于APB会扰乱介导正常感受野中拮抗中心-周边组织的神经回路。用APB处理发育中的视网膜后明显的功能变化表明，现在应该可以评估ON和OFF视网膜通路的分离与视觉系统更高层次的组织特征（如皮层细胞的方向选择性）之间的关系。
