Luminance-dependent changes of retinal output: phenomenon and mechanisms

• Applicant: Dr. Thomas Münch
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 299051345

The intensity range of environmental signals (e.g. luminance) is usually much larger than the operational range of the respective sensory neurons (e.g. photoreceptor cells). Therefore, one key property of all sensory organs is their ability to adapt, i.e. to adjust their activity to sense only a limited range, but being able to transmit more detailed information on that range. Traditionally, adaptation has been thought to maintain stability of neural activity and coding across changing conditions. For example, in the visual system, one might expect that the neural activity representing a given "visual event" is always very similar, no matter if the event happens at twilight or during mid-day. Specifically, the retinal ganglion cells, which link the eye to the brain, have classically been characterized as "ON cells" or "OFF cells" (responding to the event of light increments or decrements), as "X-cells" or "Y-cells" (integrating linearly or non-linearly across space), as transient or sustained (responding only to immediate changes or having maintained activity). We showed in a recent study (Tikidji-Hamburyan et al, Nature Neuroscience 2015) that these classical descriptions are incomplete at best: instead of being fixed, these response qualities of ganglion cells (e.g. ON vs. OFF) depend on the ambient luminance. Far from ensuring stability, adaptation in the retina results in widespread qualitative changes of retinal output. Our study therefore marks a surprising departure from traditional ganglion cell characterization. It forces us to rethink how the retina processes visual stimuli, and it has implications for our understanding of the retinal code and visual processing in general. The project proposed here investigates the interactions and mechanisms within the retina that underlie the surprising luminance-dependent response changes we have described earlier. We will employ electrophysiological experiments (single-cell patch-clamp recordings, multi-electrode array recordings) to investigate circuit interactions and retinal output in response to visual stimuli at different ambient luminance conditions, supplemented by pharmacological manipulations and immunohistochemical characterization of synaptic configurations. Specifically, the project has the following objectives: (1) What is the detailed functional relationship between the ambient light level and retinal response changes? (2) What are the synaptic interactions, the mechanisms, underlying luminance-dependent response changes? (3) What is the source of ON responses regularly observed in OFF ganglion cells? This project will also have implications for our general understanding of retinal processing and interactions of the two dozen or so parallel retinal circuits, beyond the specific question of luminance-dependent processing.

• DFG Programme: Research Grants