ON and OFF visual signaling in the retinal interneurons

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Abstract Retinal neurons utilize multiple antagonistic mechanisms to shape visual signal processing, such as ON and OFF signaling, antagonistic center-surround, rod- and cone-signaling, and transient and sustained signaling. Among those signaling mechanisms, ON vs. OFF signaling is coded to morphologically distinct groups of retinal neurons, bipolar, amacrine, and ganglion cells. Retinal neurons that ramify in the inner region of the inner plexiform layer (IPL) respond to the onset of a light stimulus, called ON cells. In contrast, OFF cells ramify in the outer region of the IPL and respond to the offset of a light stimulus. Since being discovered several decades ago, there appeared to be no exceptions to this morpho-physiological rule for ON and OFF signaling. However, recently, some exceptions have been revealed. We found that ON and OFF signaling switches in starburst amacrine cells and bipolar cells. We also found that light adaptation plays a crucial role in the ON and OFF sign switch. In the mesopic light condition, both rods and cones are active, generating a complicated interaction. However, light-evoked responses in retinal interneurons, including bipolar and amacrine cells, have not been systematically investigated over a wide range of ambient light levels. In our proposed studies, we will test the hypothesis that the rod-cone interaction in the mesopic condition converts the ON and OFF signs of light responses in retinal bipolar cells and amacrine cells. The long-term goal of the proposed study is to examine how the ON and OFF sign switch occurs in the interneuron and how this plays a role in shaping spikes in ganglion cells. We will use wholemount retinal preparations to conduct a patch clamp study of bipolar and amacrine cells to determine the visual signal signs in response to various light stimuli. Especially, we will assess the light-evoked excitatory postsynaptic potentials (L-EPSPs) over a wide range of background light conditions. We will also examine the L-EPSPs at the mesopic condition after the tissue is adapted to scotopic or photopic conditions (Aim 1). Also, we will determine how retinal antagonistic signaling systems shape the ON and OFF signs. We will test potential underlying mechanisms, including the rod-cone signaling interaction, the dopaminergic system, the antagonistic surround by inhibitory amacrine cells, and the ON-OFF signaling pathway interaction (Aim 2). Then, we will examine the outcome of the switch by conducting the Calcium imaging from the starburst amacrine cells (Aim 3). Understanding the mesopic vision is essential because both rod and cone dysfunction cause reduced vision in the mesopic vision.