Retinal direction-selective ganglion cells (DSGCs) respond selectively to motion in one direction. Recent work has shown that these cells send information to visual cortex, suggesting that they may influence conscious vision, yet the fundamental mechanisms underlying retinal direction selectivity are still not clear. Starburst Amacrine Cells (SACs) are thought to control direction selectivity by preferentially releasing GABA on one side of DSGCs. However, SACs also release acetylcholine in a symmetric manner. Although neurotransmitter co- release at other synapses has been shown to play a role in disorders such as depression, it is unknown how release of two transmitters can be differentially modulated. The main question this proposal aims to address is how SACs release these two neurotransmitters in different distributions. We will use a combination of patch- clamp electrophysiology, optogenetics, and imaging to examine the presynaptic and postsynaptic specifications that may contribute to these differences. We will also use pharmacology and calcium imaging to examine how co-release of GABA and acetylcholine is modulated and how it functions in this particular circuit. The results of this work will clarify the function of this behaviorally important sensory circuit, with potential implications for restoring vision. In additin, because of the increasingly recognized importance of neurotransmitter co-release in other areas of the brain, this study will have implications for the general understanding of chemical transmission in the nervous system.
The goal of this proposal is to clarify how cell-cell communication in the nervous system occurs at a local level and how such localized signaling can be advantageous for computation in the brain. The proposed research will answer questions about the fundamental function of cell-cell signaling in the retina and elsewhere in the central nervous system, which will be important for understanding and eventually treating neurological and neuropsychiatric disorders.
| Bleckert, Adam; Zhang, Chi; Turner, Maxwell H et al. (2018) GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells. Proc Natl Acad Sci U S A 115:E12083-E12090 |
| Koren, David; Grove, James C R; Wei, Wei (2017) Cross-compartmental Modulation of Dendritic Signals for Retinal Direction Selectivity. Neuron 95:914-927.e4 |
| Shi, Xuefeng; Barchini, Jad; Ledesma, Hector Acaron et al. (2017) Retinal origin of direction selectivity in the superior colliculus. Nat Neurosci 20:550-558 |
| Chen, Qiang; Pei, Zhe; Koren, David et al. (2016) Stimulus-dependent recruitment of lateral inhibition underlies retinal direction selectivity. Elife 5: |
| Pei, Zhe; Chen, Qiang; Koren, David et al. (2015) Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina. J Neurosci 35:13219-32 |
