Our work focuses on specialized circuitry in the inner retina. Having examined several inner retinal synapses in physiological detail, we now seek to understand how these synapses contribute to visual processing in the surrounding circuitry. We combine electrophysiology, imaging approaches and cellular/network modeling to explore dendritic integration in directionally-selective ganglion cells (DSGCs). Specifically, we have examined how directionally tuned synaptic inhibition, coming from starburst amacrine cells, and NMDA receptor-mediated input from bipolar cells combine in DSGC dendrites to achieve perfectly multiplicative scaling of postsynaptic potentials, enabling directional signals to become larger with no change in directional selectivity. A manuscript is in revision following receipt of the first round of reviews. Our work on feedback inhibition has led us to undertake a long-term effort to understand, in a systematic way, how amacrine cells contribute to visual signaling in the inner retina. With over 40 different amacrine cell subtypes, this prospect can be a bit overwhelming. To start, we have identified narrow- and wide-field amacrine cells that can be identified and manipulated by genetic means. We have acquired mouse lines in which CRE is expressed specifically in certain amacrine cells and then cross them with floxed lines enabling the CRE-expressing neurons to be silenced chemically (through CRE-dependent expression of designer receptors exclusively activated by designer drugs). The impact of this silencing on ganglion cell signaling will be examined with a microelectrode array. In addition, the cell-specific expression of calcium and voltage indicators will enable us to examine dendritic signaling in these cells that likely underlies visual processing in these cells (see Grimes, et al., 2010) that is not accessible with somatic electrophysiological recordings. A manuscript is in preparation (nearing submission) in which we have taken this approach in starburst amacrine cells. A follow-up manuscript on starburst amacrine cells is in preparation, and we are analyzing other amacrine cell subtypes in a similar fashion. We are also studying how the biophysical properties of synapses and neurons change with different phases of the circadian cycle or dark adaptation. Initially we have focused on changes in BK channel function in AII amacrine cells, which play distinct roles in night and daytime vision (see Oesch and Diamond, 2010). A manuscript is nearing submission that includes the initial physiological work.
