Date

July 2008

Document Type

Dissertation

Degree Name

Ph.D.

Institution

Oregon Health & Science University

Abstract

Understanding how information is integrated and processed in single neurons and small circuits is crucial for comprehending information processing in neural circuits, and will help elucidate the biophysical basis of cognition and cognitive dysfunction. The direction selective circuit of the retina has been an archetypical model for understanding how neural circuits process information in the brain since the direction selective ganglion cell (DSGC) was first discovered more than 40 years ago. Much progress has been made towards understanding how the direction selective circuits extracts information from moving stimuli on the retina and computes the direction of motion; however, several key questions have remained unanswered. While it had been shown that directional inhibitory inputs to the DSGC are crucial to forming directional responses, the mechanisms underlying the integration of synaptic inputs to produce directional spiking in the DSGC are unknown. Furthermore, the cell that mediates the crucial directional inhibition, the starburst amacrine cell (SBAC) has been identified, yet we do not have a complete understand how the SBAC generates this directional inhibitory signal. Using In-vitro patch-clamp recordings and two-photon calcium imaging, we show that DSGCs employ orthograde spikes originating in the dendrites to locally integrate excitatory and inhibitory synaptic inputs and signal the direction of motion, which enhances the directional selectivity of the circuit. This represents the first demonstration of how dendritic action potentials contribute to direction selectivity and more generally it is one of the first demonstrations of a physiological role for orthograde dendritic spiking in a clearly defined neural computation. By making patch-clamp electrical recordings from the SBAC, we demonstrate that the SBACs receive directional inputs and that this directional difference is boosted by tetrodotoxin-resistant voltage gated sodium channels. From these data we conclude that direction selectivity first arises presynaptically to the SBAC, and that tetrodotoxin-resistant sodium channels boost the directional signal in the SBAC. This work suggests a previously unconsidered role for the mechanism that generates directional signals in the SBAC and more generally demonstrates the physiological role of the non-typical tetrodotoxin-resistant sodium channels in a clearly defined neural computation.

Identifier

doi:10.6083/M4G15XTB

Division

Neuroscience Graduate Program

School

School of Medicine

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