Physiology and Organization of Retinal Cell Types

Project Abstract Neurons in the vertebrate retina are classified into well-defined types and organized in a layered structure according to a set of organizational principles. In the mammalian retina, the dendritic and axonal processes of second- and third-order neurons are strategically positioned to utilize the conventional ON and OFF segregation of the inner plexiform layer (IPL). However, cell types that ramify in the distal margin of the IPL, known as the accessory ON layer (AOL), often exhibit paradoxical ON responses that require anatomical and physiological explanation. Recently, we discovered a new group of bipolar cell populations that co-stratify with M1 photoreceptive ganglion cells and dopaminergic amacrine cells (DACs) in the AOL and display ON light responses. The goal of this proposal is to understand the organization and function of these noncanonical bipolar cells (NBCs) in the retina. To achieve this, we have developed an innovative experimental approach that integrates advanced electrophysiological recordings with two-photon Ca and glutamate imaging of genetically labeled neurons in a powerful wholemount retinal preparation. This functional approach is further enhanced by ultrastructural reconstructions of NBC synaptic circuitry using serial block EM connectomics. There are three specific aims: (1) Understand the physiological responses and anatomical properties of NBCs in the mouse retina, (2) Understand the synaptic physiology of glutamate signaling in the accessory ON layer (AOL), (3) Connectomic and functional characterization of NBC synaptic circuits. Results from this study are expected to provide new insights into the function and organization of NBCs in the AOL and their interactions with other retinal neurons.