Di Berardino Claudia, Estay Sebastián F, Alcaino Alejandro, Chávez Andrés E
Programa de Doctorado en Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, 2340000, Valparaíso, Chile.
Instituto de Neurociencias, Facultad de Ciencias, Universidad de Valparaíso, 2340000, Valparaíso, Chile.
Biol Res. 2025 Mar 4;58(1):11. doi: 10.1186/s40659-025-00594-6.
Serotonin (5-HT) is known to be synthesized and accumulated in the vertebrate retina through the 5-HT transporter, SERT. While manipulation of the serotonergic system has been shown to impact visual processing, the role of 5-HT and SERT as modulators of retinal synaptic function remains poorly understood.
Using mouse retinal slices, we show that acute application of 5-HT produces a cell-type specific reduction in light-evoked excitatory responses (L-EPSC) in ON-OFF retinal ganglion cells (RGCs), but not in ON RGCs. Similarly, increasing 5-HT tone by acute application of citalopram, a selective 5-HT reuptake inhibitor, also reduces L-EPSC in ON-OFF RGCs while not affecting ON RGCs. Importantly, citalopram-mediated reduction of L-EPSC was absent in ON-OFF RGCs recorded from SERT null retina, highlighting the role of SERT in regulating light-evoked responses in RGCs. The effects of both exogenous and endogenous 5-HT on L-EPSC in ON-OFF RGCs are likely due to a presynaptic reduction in excitatory synaptic strength as 5-HT and citalopram reduced the frequency but not the amplitude of spontaneous excitatory currents (sEPSCs) in ON-OFF RGCs. Moreover, 5-HT and citalopram had no effect on currents elicited by the direct activation of postsynaptic receptors in RGCs by brief application of glutamate in the inner retina.
Altogether these findings indicate that 5-HT modulates excitatory inputs onto RGCs in a cell-type specific manner and highlight that in the adult mouse retina, 5-HT-mediated effects onto RGCs are tightly controlled by the 5-HT transporter SERT.
已知血清素（5-羟色胺，5-HT）通过5-HT转运体（SERT）在脊椎动物视网膜中合成和积累。虽然已经表明对血清素能系统的操纵会影响视觉处理，但5-HT和SERT作为视网膜突触功能调节剂的作用仍知之甚少。
使用小鼠视网膜切片，我们发现急性应用5-HT会使开-关型视网膜神经节细胞（RGC）的光诱发兴奋性反应（L-EPSC）产生细胞类型特异性降低，但对开型RGC没有影响。同样，通过急性应用选择性5-HT再摄取抑制剂西酞普兰来增加5-HT水平，也会降低开-关型RGC的L-EPSC，而不影响开型RGC。重要的是，在从SERT基因敲除视网膜记录的开-关型RGC中，西酞普兰介导的L-EPSC降低不存在，这突出了SERT在调节RGC光诱发反应中的作用。外源性和内源性5-HT对开-关型RGC中L-EPSC的影响可能是由于兴奋性突触强度的突触前降低，因为5-HT和西酞普兰降低了开-关型RGC中自发兴奋性电流（sEPSC）的频率但不影响其幅度。此外，5-HT和西酞普兰对通过在内层视网膜中短暂应用谷氨酸直接激活RGC突触后受体所引发的电流没有影响。
总之，这些发现表明5-HT以细胞类型特异性方式调节对RGC的兴奋性输入，并突出了在成年小鼠视网膜中，5-HT对RGC的介导作用受到5-HT转运体SERT的严格控制。
