Abstract
Direction selectivity is an important feature throughout the visual system, and this arises from within the intricate neural network of the retina. The ON-OFF direction selective ganglion cells (DSGCs) in the mammalian retina respond vigorously to an object moving in their preferred direction but show little or no response at all to movement in their null (the opposite) direction. In this dissertation, there are two independent studies of the DSGCs, one examining their maturation process and the other investigating their synaptic mechanism. Although it has been known that the basic neural circuit of direction selectivity is established at around the time of eye opening, it is less known if the four DSGC subtypes (i.e., those responsible for the detection of motion in the superior, inferior, anterior, and posterior directions of the visual field) can be unambiguously distinguished and their preferred directions are aligned with four canonical axes at this developmental stage. By examining the preferred directions of DSGCs in P10-12 rabbit retinas and characterizing their distribution pattern, in the first study, we have shown that the preferred directions of DSGCs at eye opening are not distinctly segregated but rather are diffusely distributed along the four canonical axes. Furthermore, the fact that the direction tuning strength of DSGCs at P10-12 is weaker than that in adults, and this was found not to be correlated with their preferred directions, suggests that the maturations of direction selectivity and preferred direction are independent processes. In addition, we also found that the subtypes of DSGCs, which do not display tracer coupling pattern in the adult, show extensive coupling at P10-12. Taken together, the first study supports that the significant refinement after eye opening is required for the development of the four functional DSGC subtypes in the rabbit retina. In addition to the prominent trigger feature of direction selectivity, it is also known that the spiking response of DSGCs is context dependent (i.e., the cell responds differently depending on the spatiotemporal relationship of visual stimuli between the receptive field center and its surround), though the underlying synaptic mechanism is not fully understood. The second study was to identify the key components of the contextual phase-tuning of DSGCs. By using loose on-cell and whole-cell patch clamp recording, effects of the phase difference between of the center and surround moving gratings on the responses of the DSGC were investigated in P14-25 rabbit retinas. Consistent with the previous study, we have shown that spike responses of DSGCs to the center drifting grating are strongly suppressed by the surround grating when the two gratings are moving in-phase, but are only minimally suppressed when the grating are moving out-of-phase. Importantly, the excitatory inputs to the DSGC are also contextually tuned, regardless whether the gratings move in the preferred or the null direction. By removing the nicotinic cholinergic input, we have shown that the glutamatergic input from bipolar cells is already contextually tuned. Further experiments showed that the tuning is mediated by GABAergic inputs through the activation of both GABAA and GABAC receptors. Taken together, the second study suggests that contextual effect of DSGCs is mediated predominantly by the tuning of the excitatory inputs from bipolar cells via GABAergic lateral inhibition from the receptive field surround. In conclusion, by elucidating the maturation process and synaptic mechanism of DSGCs in the rabbit retina, this dissertation sheds light on how intricate neural circuits develop and function in the mammalian retina. Understanding the activity-dependent refinement and synaptic connection of information processing in the retina will potentially illuminate the key steps in developing therapeutic strategies aimed at restoring vision and brain function.