Li, C. Liu, and B. Sun for technical advice. This work was supported by Singapore Millennium Foundation (D.K), Duke-NUS funding, MOE2008-T2-1-048 and NRF-RF2009-02 (H.W.), Temasek Life Sciences Laboratory, and Singapore (F.Y.). “
“During the day/night cycle, our visual system faces the challenge of operating over E7080 research buy a light intensity range that covers more than nine orders of magnitude (Rodieck, 1998). To meet this challenge, the retina undergoes dark and light adaptation at all levels of processing, including

the various stages of rod-driven circuitry, which mediate dim-light vision (Dunn et al., 2006 and Shapley and Enroth-Cugell, 1984). The types of retinal neurons participating in the primary rod circuit and addressed in this study are illustrated in Figure 1A. Protein Tyrosine Kinase inhibitor Rod photoreceptors provide glutamatergic input to a single class of rod bipolar cells that depolarize upon light stimulation (depolarizing “ON” bipolar cells, DBCs), a response triggered by cessation of glutamate release from rod synapses. Axon terminals of rod DBCs are located in the inner retina, where they form synapses with AII amacrine cells.

The signals are further processed by cone ON bipolar and retinal ganglion cells and transmitted to the brain via the optic nerve. The strength and duration of light signals traveling through the rod-driven circuit are shaped by two classes of retinal neurons (Wässle, 2004). Amacrine cells regulate the synaptic output of rod DBCs by GABAergic enough and glycinergic inputs, providing both lateral and temporal inhibitory feedback (Chávez et al., 2010, Eggers and Lukasiewicz, 2006 and Tachibana and Kaneko, 1987). Horizontal cell axon terminals provide lateral feedback inhibition directly onto rods (Babai and Thoreson, 2009) and potentially feedforward inhibition onto bipolar cell dendrites (Yang and Wu, 1991). However, the precise mechanisms by which horizontal cells communicate with other neurons remain controversial (Kamermans and Spekreijse, 1999). It also remains unknown whether horizontal cells play a direct role in setting the light sensitivity

of the rod-driven circuitry. Dopamine, another major neurotransmitter in the retina, is produced by a single class of amacrine cells (Figure 1A) and has long been known to modulate retinal circuitry to favor cone-driven pathways during the daytime (Witkovsky, 2004). The goal of this study was to investigate whether dopamine is involved in controlling the light sensitivity and adaptation of rod-driven DBCs. We now demonstrate that dopamine is also critical for sensitizing rod-driven DBC responses in the dark and under dim light. This sensitizing effect of dopamine is mediated only by D1-type dopamine receptors (D1R), with horizontal cells serving as a plausible dopamine target. We further demonstrate that this D1R-dependent mechanism is conveyed through a GABAergic input via GABAC receptors (GABACR) expressed in rod-driven DBCs.