Zalutsky R A, Miller R F
Washington University School of Medicine, Department of Ophthalmology, St. Louis, Missouri 63110.
J Neurosci. 1990 Feb;10(2):383-93. doi: 10.1523/JNEUROSCI.10-02-00383.1990.
The neuropeptide somatostatin (SS) has been localized to neurons of the rabbit retina by immunochemical and biochemical methods (Sagar et al., 1982, 1986; Marshak and Yamada 1984). We examined the effects of bath-applied SS on neurons of the rabbit retina, using intra- and extracellular electrophysiological techniques in an in vitro retina eyecup preparation. All commonly encountered ganglion cell receptive field types were affected by SS, and the effects were of 3 kinds: The first was a general excitation, occurring with a threshold concentration of about 100 nM; the onset of the excitation was too slow (seconds) for SS to participate in any rapid light-evoked responses. The second SS effect was an increase in the "signal-to-noise ratio," defined here as the ratio of light-evoked to spontaneous spiking, which resulted from a decrease in spontaneous activity and, usually, a concomitant increase in light-evoked spiking. The third effect was a shift in center-surround balance towards a more dominant center. The signal-to-noise and center-surround effects were evident at concentrations as low as 0.5 nM; both were slow onset (tens of seconds) and long lasting (tens of minutes). SS acted at multiple levels within the retinal circuitry to produce the observed changes in ganglion cell output. These effects included direct actions on ganglion and amacrine cells, and a decrease in the efficiency with which horizontal cells could drive the retinal network. At least part of these SS actions on third-order neurons resulted from a decrease in conductance to ions with an equilibrium potential more positive than dark membrane potential. The degradation-resistant SS agonist SMS201-995 had effects qualitatively and quantitatively similar to those of SS, suggesting that SS may be degraded slowly enough to act at a distance from its sites of release. While no adequate SS antagonist is available, the greater sensitivity to exogenous SS, in retinas depleted of their SS content (with cysteamine), suggests a role for endogenous SS. The potency of SS also reinforces this view. The results of this study suggest that SS may be a neuromodulator in the rabbit retina, producing long-lasting changes in the "signal-to-noise" discharge pattern and center-surround balance of ganglion cells.
通过免疫化学和生物化学方法（萨加尔等人，1982年、1986年；马沙克和山田，1984年）已将神经肽生长抑素（SS）定位到兔视网膜的神经元。我们在体外视网膜眼杯制备中使用细胞内和细胞外电生理技术，研究了浴加SS对兔视网膜神经元的影响。所有常见的神经节细胞感受野类型均受SS影响，且影响有3种：第一种是一般兴奋，在约100 nM的阈值浓度时出现；兴奋的起始太慢（数秒），以至于SS无法参与任何快速的光诱发反应。SS的第二种作用是“信噪比”增加，此处定义为光诱发的与自发放电的比率，这是由于自发活动减少，且通常伴随光诱发放电增加所致。第三种作用是中心-周边平衡向更占主导地位的中心转移。信噪比和中心-周边效应在低至0.5 nM的浓度时就很明显；两者都是缓慢起始（数十秒）且持续时间长（数十分钟）。SS在视网膜回路的多个水平起作用，以产生神经节细胞输出中观察到的变化。这些作用包括对神经节细胞和无长突细胞的直接作用，以及水平细胞驱动视网膜网络效率的降低。SS对三级神经元的这些作用至少部分是由于对平衡电位比暗膜电位更正的离子的电导降低所致。抗降解的SS激动剂SMS201-995的作用在质量和数量上与SS相似，这表明SS的降解可能足够缓慢，从而能在远离其释放部位起作用。虽然没有合适的SS拮抗剂，但在其SS含量耗尽（用半胱胺）的视网膜中对外源SS的敏感性更高，这表明内源性SS起作用。SS的效力也强化了这一观点。本研究结果表明，SS可能是兔视网膜中的一种神经调节剂，可在神经节细胞的“信噪比”放电模式和中心-周边平衡方面产生持久变化。
