Information processing in the brain is orchestrated by neural circuits that are optimized to extract relevant features from the environment. In particular, visual circuits sensitive to contrast, texture, color, motion, and orientation help create internal representations of our visual world and guide animal behavior. Visual motion enhances saliency of perceived objects and is critical for coordinating animal reflexes and more complicated behaviors, such as flight-or-fight responses. This dissertation is divided in two parts. Part I focuses on visual processing in the mammalian retina, particularly visual feature selectivity across different biological length scales. As it will be described in further detail in Chapter 1, motion sensitivity is first computed in the retina by dedicated circuits that give rise to direction and axial-selective responses. Understanding the mechanisms underlying motion detection in the mammalian retina can provide a foundation for describing complex neural computations in higher order brain areas.
In the mammalian retina, the detection of motion direction, or direction selectivity, is first observed in the dendrites of starburst amacrine cells (SACs). Individual dendritic sectors of SACs exhibit centrifugal preference for the direction of motion, meaning that they are maximally activated by objects moving from soma to tip and only weakly activated by motion in opposite direction, tip to soma. This remarkable dendritic computation can be achieved in such a compact neuron because dendritic sectors in SACs are eletrotonically isolated from each other; however, the mechanisms orchestrating this fine balance between integration and isolation is not completely understood. In Chapter 2, we look into the contributions of synaptic mechanisms and cell-intrinsic properties to compartmentalized signaling in SACs. Our results highlight how metabotropic glutamate receptor II (mGluR2) and voltage-gated potassium channels of subfamily 3 (Kv3) regulate dendritic excitability and the initiation of non-linear calcium events along the dendrites of SACs.
The direction selective signals in the dendrites of SACs are relayed to direction-selective ganglion cells, which transform inhibitory and excitatory inputs into a direction-selective spiking output that is transmitted to downstream visual nuclei, including the superior colliculus and visual thalamus. Asymmetric GABAergic inhibition from SACs to DSGCs is considered the central mechanism for direction selectivity in DSGCs; although, SACs also release acetylcholine which activate nicotinic acethylcholine receptors DSGCs and represents a significant fraction of total excitatory charge in these neurons. In Chapter 3, we look into parallel mechanisms for retinal direction selectivity by using conditional transgenic strategies to manipulate individual synapses in the direction selective circuit. Results from this study highlight how excitatory mechanisms contribute to direction selectivity and expands on the roles of SACs in visual processing. In Chapter 4, I worked together with external collaborators to determine the extent of which retinal direction selectivity influences signaling in a major retinorecipient target, the superior colliculus.
Then, I characterized transgenic methods to express GCaMP6 in retinal ganglion cells (RGCs) in effort to improve and streamline functional imaging in the output neurons of the retina (Chapter 5). Using the Vglut2-IRES-Cre mouse line to express GCaMP6 in RGCs, I monitored the abundance of motion sensitive receptive fields across development and characterized the response properties of On-Off orientation sensitive, or axis selective, receptive fields in Chapter 6.
Part II of this dissertation focuses on next-generation devices and tools for the interrogation of neural circuits. Currently, biological systems are interrogated with bulky electrodes, which tend to be highly invasive because of their large-scale dimensions and mechanical mismatch with targeted tissue. As described in Chapter 7, recent advances in nanoscale technologies have facilitated the development of novel materials that are well suited for biological applications, including flexible alternatives to rigid and invasive probes. In Chapter 8, I discuss the fabrication of porous silicon nanowires and their application as optical tools for neuronal stimulation. Lastly, in Chapter 9 we describe a carbon-based supercapacitor and demonstrate efficient stimulation in neural and cardiac tissues.
|Advisor:||Wei, Wei, Tian, Bozhi|
|Commitee:||Maunsell, John, Eatock, Ruth A., Sheffield, Mark|
|School:||The University of Chicago|
|School Location:||United States -- Illinois|
|Source:||DAI-B 82/3(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Biophysics, Materials science|
|Keywords:||computation, dendrites, direction selectivity, neural circuits, neuromodulation, vision|
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