Description:

Steven H. DeVries, M.D., Ph.D.

In order to encode incident light over a wide intensity and temporal frequency range, cone photoreceptors have a high energy throughput. However, it is a general principle that signals are represented with greater energetic efficiency when carried by more units signaling at lower rates. Hence, one of the first steps in signal processing in the visual system involves the sorting of cone signals into 12-14 parallel bipolar cell pathways. Under conditions of daylight, the cone outer segment converts the light from a visual scene into a time-varying membrane voltage signal, which is then re-encoded as a rate of vesicle release at the cone synapse. The spatiotemporal glutamate gradient in the cone synaptic cleft is then sampled by the dendritic contacts of more than 12 different bipolar cell types. My lab focuses on how differences in sampling produce different signals in the five types of Off (ionotropic glutamate receptor-expressing) bipolar cells. Using a combination of cell pair recording, super-resolution microscopy, and rapid receptor perfusion, I identify a threshold-based strategy in which the individual Off bipolar cell types respond to cone transmitter release and encode the visual signal over different light decrement ranges. I examine the mechanisms that underlie the threshold response differences. Differences in response threshold result from type-specific distances between ribbon vesicle release sites and the sites of bipolar cell cone contacts, the precise number of contacts that each bipolar cell makes with a cone, the glutamate affinity of the different kainate and AMPA receptors on the Off bipolar cell types, and the localization of glutamate transporter plaques on the cone terminal surface. The response differences that arise at the cone synapse are further modified by bipolar cell type-specific voltage-dependent membrane currents and amacrine cell inputs to produce the excitatory output that drives the responses of the different retinal ganglion cell types.