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. Our most recent work has focused on a previously unknown signaling pathway in night vision circuitry. We have discovered that AII amacrine cells make direct, powerful inhibitory synaptic contacts onto the somata of OFF retinal ganglion cells. We have found that this confers great sensitivity onto the OFF pathways, particularly when stimulated by small, dim spots of light. We are working to determine whether this constitutes the primary pathway for transmitting single photon signals through the mouse retina. A manuscript is under preparation. We are continuing our examination of starburst amacrine cell (SAC) function in the mouse retina by undertaking a machine learning approach to identifying individual SACs within the dense plexus of fluorescent processes in the ChAT-tdTomato mouse retina. Our goal is to record Ca signals in all of the output synapses within the SAC network, then use the machine learning algorithms to associate each synapse with its respective SAC. We are also examining a novel mechanism by which a single, densely expressed amacrine cell type may provide the link between light evoked activity and control of the retinal vasculature. Finally, we are examining the circuit mechanisms underlying retinal remodeling during retinal degenerative diseases. We are using the rd10 mouse model of retinitis pigmentosa to examine how pharmacological intervention may limit circuit oscillations and preserve healthy circuitry, thereby providing a better foundation for subsequent therapies to restore visual sensitivity in the absence of photoreceptors.

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Support Year
6
Fiscal Year
2019
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Poleg-Polsky, Alon; Ding, Huayu; Diamond, Jeffrey S (2018) Functional Compartmentalization within Starburst Amacrine Cell Dendrites in the Retina. Cell Rep 22:2898-2908
Diamond, Jeffrey S (2017) Inhibitory Interneurons in the Retina: Types, Circuitry, and Function. Annu Rev Vis Sci 3:1-24
Poleg-Polsky, Alon; Diamond, Jeffrey S (2016) NMDA Receptors Multiplicatively Scale Visual Signals and Enhance Directional Motion Discrimination in Retinal Ganglion Cells. Neuron 89:1277-1290
Poleg-Polsky, Alon; Diamond, Jeffrey S (2016) Retinal Circuitry Balances Contrast Tuning of Excitation and Inhibition to Enable Reliable Computation of Direction Selectivity. J Neurosci 36:5861-76
Ding, Huayu; Smith, Robert G; Poleg-Polsky, Alon et al. (2016) Species-specific wiring for direction selectivity in the mammalian retina. Nature 535:105-10
Poleg-Polsky, Alon (2015) Effects of Neural Morphology and Input Distribution on Synaptic Processing by Global and Focal NMDA-Spikes. PLoS One 10:e0140254
Graydon, Cole W; Cho, Soyoun; Diamond, Jeffrey S et al. (2014) Specialized postsynaptic morphology enhances neurotransmitter dilution and high-frequency signaling at an auditory synapse. J Neurosci 34:8358-72