Serotonin regulates in a cell-type specific manner light-evoked response and synaptic activity in mouse retinal...

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.