Maguire G, Lukasiewicz P, Werblin F
Neurobiology Group, University of California, Berkeley 94720.
J Neurosci. 1989 Feb;9(2):726-35. doi: 10.1523/JNEUROSCI.09-02-00726.1989.
The neural circuitry and pharmacology underlying transient signal formation at the bipolar-amacrine cell interface were studied. Synaptic currents were measured with whole cell patch clamp in retinal slices. Cell types were identified with Lucifer yellow staining. Activity was initiated with puffs of kainate of known time course and spatial spread delivered at bipolar dendrites. OFF bipolar cells responded to kainate with a sustained inward current, but ON bipolar cells were silent. Two types of amacrine cell were found: (1) narrow field cells, with processes that extended laterally less than 200 microns, responding with a sustained inward current, and (2) wide field cells, with processes that extended laterally by up to 1 mm, responding with a brief transient inward current followed by a more sustained outward current. We pharmacologically dissected the synaptic interactions underlying the transient current in the wide field amacrine cell. In the presence of 5-aminovaleric acid (AVA), the time course of this transient current was increased so that it resembled the response of bipolar cells. Because AVA is a GABAB antagonist, it appears to block an opposing signal that truncates the sustained excitatory bipolar input, thereby generating the transient. GABAB specificity is confirmed by (1) block of the transient inward current by baclofen, a GABAB agonist, and (2) block of the baclofen effect by AVA. The site of GABAB action appears to be presynaptic to the amacrine cell membrane because neither baclofen nor AVA, in combination with picrotoxin, had a direct effect at the amacrine cell membrane. GABAB receptors are often found at presynaptic terminals where they modulate calcium or potassium conductances. It has been shown that bipolar cell terminals receive a GABAergic synaptic input (Vaughn et al., 1981; Wu et al., 1981; Tachibana and Kaneko, 1987). The narrow field sustained-responding amacrine cells appear to be GABAergic (Werblin et al., 1988). This suggests that transient activity measured in wide field amacrine cells is formed at a population of bipolar cell terminals by GABAergic feedback from narrow field amacrine cells at GABAB receptors.
研究了双极细胞-无长突细胞界面处瞬态信号形成的神经回路和药理学机制。在视网膜切片中，用全细胞膜片钳记录突触电流。通过荧光黄染色鉴定细胞类型。在双极细胞树突处施加已知时间进程和空间扩散的海人酸微喷射来引发活动。离双极细胞对海人酸产生持续内向电流反应，但开双极细胞无反应。发现了两种类型的无长突细胞：（1）窄场细胞，其突起横向延伸小于200微米，产生持续内向电流反应；（2）宽场细胞，其突起横向延伸可达1毫米，产生短暂的瞬态内向电流，随后是更持续的外向电流。我们从药理学角度剖析了宽场无长突细胞中瞬态电流背后的突触相互作用。在5-氨基戊酸（AVA）存在的情况下，该瞬态电流的时间进程延长，使其类似于双极细胞的反应。由于AVA是一种GABAB拮抗剂，它似乎阻断了一个相反的信号，该信号截断了双极细胞持续的兴奋性输入，从而产生瞬态。GABAB特异性通过以下方式得到证实：（1）GABAB激动剂巴氯芬阻断瞬态内向电流；（2）AVA阻断巴氯芬的作用。GABAB的作用位点似乎在无长突细胞膜的突触前，因为巴氯芬和AVA与苦味毒联合使用时，对无长突细胞膜没有直接作用。GABAB受体经常出现在突触前终末，在那里它们调节钙或钾电导。已经表明双极细胞终末接受GABA能突触输入（沃恩等人，1981年；吴等人，1981年；立花和金子，1987年）。窄场持续反应的无长突细胞似乎是GABA能的（韦尔布林等人，1988年）。这表明在宽场无长突细胞中测量到的瞬态活动是由窄场无长突细胞在GABAB受体处的GABA能反馈在一群双极细胞终末形成的。
