Sanyal Subhabrata, Narayanan Radhakrishnan, Consoulas Christos, Ramaswami Mani
Department of Molecular & Cellular Biology, Box 210106 University of Arizona, 1007 E, Lowell Street, Tucson AZ 85721, USA.
BMC Neurosci. 2003 Sep 11;4:20. doi: 10.1186/1471-2202-4-20.
The transcription factor AP1 mediates long-term plasticity in vertebrate and invertebrate central nervous systems. Recent studies of activity-induced synaptic change indicate that AP1 can function upstream of CREB to regulate both CREB-dependent enhancement of synaptic strength as well as CREB-independent increase in bouton number at the Drosophila neuromuscular junction (NMJ). However, it is not clear from this study if AP1 functions autonomously in motor neurons to directly modulate plasticity.
Here, we show that Fos and Jun, the two components of AP1, are abundantly expressed in motor neurons. We further combine immunohistochemical and electrophysiological analyses with use of a collection of enhancers that tightly restrict AP1 transgene expression within the nervous system to show that AP1 induction or inhibition in, but not outside of, motor neurons is necessary and sufficient for its modulation of NMJ size and strength.
By arguing against the possibility that AP1 effects at the NMJ occur via a polysynaptic mechanism, these observations support a model in which AP1 directly modulates NMJ plasticity processes through a cell autonomous pathway in the motor neuron. The approach described here may serve as a useful experimental paradigm for analyzing cell autonomy of genes found to influence structure and function of Drosophila motor neurons.
转录因子AP1介导脊椎动物和无脊椎动物中枢神经系统的长期可塑性。最近关于活动诱导的突触变化的研究表明，AP1可在CREB上游发挥作用，以调节果蝇神经肌肉接头（NMJ）处CREB依赖的突触强度增强以及CREB非依赖的轴突终扣数量增加。然而，从这项研究中尚不清楚AP1是否在运动神经元中自主发挥作用以直接调节可塑性。
在这里，我们表明AP1的两个组成部分Fos和Jun在运动神经元中大量表达。我们进一步将免疫组织化学和电生理分析与一系列增强子结合使用，这些增强子严格限制神经系统内AP1转基因的表达，以表明在运动神经元内而非其外诱导或抑制AP1对于其调节NMJ大小和强度是必要且充分的。
通过排除AP1在NMJ处的作用通过多突触机制发生的可能性，这些观察结果支持了一种模型，即AP1通过运动神经元中的细胞自主途径直接调节NMJ可塑性过程。这里描述的方法可能作为一种有用的实验范式，用于分析发现影响果蝇运动神经元结构和功能的基因的细胞自主性。
