Circadian Behavioral Responses to Light and Optic Chiasm-Evoked Glutamatergic EPSCs in the Suprachiasmatic Nucleus of ipRGC Conditional vGlut2 Knock-Out Mice.
Circadian Behavioral Responses to Light and Optic Chiasm-Evoked Glutamatergic EPSCs in the Suprachiasmatic Nucleus of ipRGC Conditional vGlut2 Knock-Out Mice.
复制标题
DOI：
10.1523/eneuro.0411-17.2018
复制
发表时间：
2018-05
期刊：
影响因子：
3.4
通讯作者：
Pickard GE
中科院分区：
文献类型：
--
作者：
Moldavan MG;Sollars PJ;Lasarev MR;Allen CN;Pickard GE
光敏视网膜神经节细胞(IpRGCs)本质上支配着下丘脑视交叉上核(SCN)，这是一种起生物钟作用的生理振荡器。IpRGC使用囊泡谷氨酸转运体2(VGlut2)将谷氨酸包装到突触小泡中，光诱发的SCN生物钟的重置被广泛地归因于ipRGC谷氨酸能神经传递。脑垂体腺苷环化酶激活多肽(PACAP)也被包裹在ipRGCs的囊泡中，在SCN中PACAP可能与谷氨酸共同释放。在小鼠的ipRGC中，vGlut2被有条件地删除[条件性敲除(CKO)]，其异常的光携带和残留的衰减光反应被归因于ipRGC PACAP的释放。然而，没有直接证据表明所有的ipRGC谷氨酸能神经传递在vGlut2 cKO中被消除。在这里，我们研究了两个ipRGC vGlut2 CKO小鼠品系在几种光照条件下SCN介导的行为反应以及SCN中的ipRGC谷氨酸能神经传递。昼夜行为反应从对光的非常有限的反应到接近正常的光携带。收集行为学数据后，制作下丘脑脑片，刺激视交叉，记录SCN神经元诱发的EPSCs。在cKO中，记录到谷氨酸能eEPSC，所有eEPSC参数(刺激阈值、幅度、上升时间或峰值时间以及刺激强度以引起最大反应)与对照组相似。我们得出结论，在两个vGlut2 CKO小鼠系中，数量可变但功能显著的ipRGC继续释放谷氨酸。因此，这些CKO小鼠系中残留的SCN介导的光反应不能完全归因于ipRGC PACAP的释放。
Intrinsically photosensitive retinal ganglion cells (ipRGCs) innervate the hypothalamic suprachiasmatic nucleus (SCN), a circadian oscillator that functions as a biological clock. ipRGCs use vesicular glutamate transporter 2 (vGlut2) to package glutamate into synaptic vesicles and light-evoked resetting of the SCN circadian clock is widely attributed to ipRGC glutamatergic neurotransmission. Pituitary adenylate cyclase-activating polypeptide (PACAP) is also packaged into vesicles in ipRGCs and PACAP may be coreleased with glutamate in the SCN. vGlut2 has been conditionally deleted in ipRGCs in mice [conditional knock-outs (cKOs)] and their aberrant photoentrainment and residual attenuated light responses have been ascribed to ipRGC PACAP release. However, there is no direct evidence that all ipRGC glutamatergic neurotransmission is eliminated in vGlut2 cKOs. Here, we examined two lines of ipRGC vGlut2 cKO mice for SCN-mediated behavioral responses under several lighting conditions and for ipRGC glutamatergic neurotransmission in the SCN. Circadian behavioral responses varied from a very limited response to light to near normal photoentrainment. After collecting behavioral data, hypothalamic slices were prepared and evoked EPSCs (eEPSCs) were recorded from SCN neurons by stimulating the optic chiasm. In cKOs, glutamatergic eEPSCs were recorded and all eEPSC parameters examined (stimulus threshold, amplitude, rise time or time-to-peak and stimulus strength to evoke a maximal response) were similar to controls. We conclude that a variable number but functionally significant percentage of ipRGCs in two vGlut2 cKO mouse lines continue to release glutamate. Thus, the residual SCN-mediated light responses in these cKO mouse lines cannot be attributed solely to ipRGC PACAP release.