The Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA.
J Neurophysiol. 2011 Nov;106(5):2285-302. doi: 10.1152/jn.00641.2011. Epub 2011 Jul 27.
The balance of inhibitory to excitatory (I/E) synaptic inputs is thought to control information processing and behavioral output of the central nervous system. We sought to test the effects of the decreased or increased I/E ratio on visual circuit function and visually guided behavior in Xenopus tadpoles. We selectively decreased inhibitory synaptic transmission in optic tectal neurons by knocking down the γ2 subunit of the GABA(A) receptors (GABA(A)R) using antisense morpholino oligonucleotides or by expressing a peptide corresponding to an intracellular loop of the γ2 subunit, called ICL, which interferes with anchoring GABA(A)R at synapses. Recordings of miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory PSCs (mEPSCs) showed that these treatments decreased the frequency of mIPSCs compared with control tectal neurons without affecting mEPSC frequency, resulting in an ∼50% decrease in the ratio of I/E synaptic input. ICL expression and γ2-subunit knockdown also decreased the ratio of optic nerve-evoked synaptic I/E responses. We recorded visually evoked responses from optic tectal neurons, in which the synaptic I/E ratio was decreased. Decreasing the synaptic I/E ratio in tectal neurons increased the variance of first spike latency in response to full-field visual stimulation, increased recurrent activity in the tectal circuit, enlarged spatial receptive fields, and lengthened the temporal integration window. We used the benzodiazepine, diazepam (DZ), to increase inhibitory synaptic activity. DZ increased optic nerve-evoked inhibitory transmission but did not affect evoked excitatory currents, resulting in an increase in the I/E ratio of ∼30%. Increasing the I/E ratio with DZ decreased the variance of first spike latency, decreased spatial receptive field size, and lengthened temporal receptive fields. Sequential recordings of spikes and excitatory and inhibitory synaptic inputs to the same visual stimuli demonstrated that decreasing or increasing the I/E ratio disrupted input/output relations. We assessed the effect of an altered I/E ratio on a visually guided behavior that requires the optic tectum. Increasing and decreasing I/E in tectal neurons blocked the tectally mediated visual avoidance behavior. Because ICL expression, γ2-subunit knockdown, and DZ did not directly affect excitatory synaptic transmission, we interpret the results of our study as evidence that partially decreasing or increasing the ratio of I/E disrupts several measures of visual system information processing and visually guided behavior in an intact vertebrate.
抑制性到兴奋性（I/E）突触输入的平衡被认为控制着中枢神经系统的信息处理和行为输出。我们试图通过敲低 GABA(A) 受体（GABA(A)R）γ2 亚基的反义形态发生素寡核苷酸或表达对应于 γ2 亚基细胞内环的肽（称为 ICL）来选择性地降低视顶盖神经元中的抑制性突触传递，从而测试降低或增加 I/E 比值对视光回路功能和视觉引导行为的影响。记录微小抑制性突触后电流（mIPSCs）和微小兴奋性 PSCs（mEPSCs）表明，与对照视顶盖神经元相比，这些处理降低了 mIPSCs 的频率，而不影响 mEPSC 的频率，导致 I/E 突触输入的比值降低约 50%。ICL 表达和 γ2 亚基敲低也降低了视神经诱发的突触 I/E 反应的比值。我们从视顶盖神经元记录视觉诱发反应，其中突触 I/E 比值降低。降低视顶盖神经元中的突触 I/E 比值增加了全视野视觉刺激反应的第一峰潜伏期的方差，增加了视顶盖电路中的递归活动，扩大了空间感受野，并延长了时间整合窗口。我们使用苯二氮䓬类药物，地西泮（DZ）来增加抑制性突触活动。DZ 增加了视神经诱发的抑制性传递，但不影响诱发的兴奋性电流，导致 I/E 比值增加约 30%。用 DZ 增加 I/E 比值会降低第一峰潜伏期的方差，减小空间感受野的大小，并延长时间感受野。对相同视觉刺激的尖峰和兴奋性和抑制性突触输入的连续记录表明，降低或增加 I/E 比值会破坏输入/输出关系。我们评估了改变 I/E 比值对视顶盖介导的视觉回避行为的影响，这种行为需要视顶盖。增加和降低视顶盖神经元中的 I/E 阻断了视顶盖介导的视觉回避行为。由于 ICL 表达、γ2 亚基敲低和 DZ 没有直接影响兴奋性突触传递，我们将我们研究的结果解释为证据，证明部分降低或增加 I/E 比值会破坏完整脊椎动物中几种视觉系统信息处理和视觉引导行为的测量。
