Physiology and Anatomy of rarely encountered ganglion cells in the mammalian retina

There are about 15-20 types of retinal ganglion cells (RGCs), each providing a filtered representation of the visual input to the brain. The diverse receptive-field properties of different types of RGCs are formed by the retinal interneurons that provide the synaptic input, including 10–12 types of excitatory bipolar cells and 40–50 types of inhibitory amacrine cells. Many of the RGCs have a concentric organization, with an ON-center and OFF-surround or vice versa, and there is a good understanding of how their receptive fields are generated. However, much remains to be discovered about the synaptic mechanisms that underlie the responses of other RGCs with complex receptive-field properties. In this thesis, I have studied several types of complex RGCs that are rarely encountered, including the uniformity detector (UD), the ON direction-selective ganglion cell (DSGC) and the transient ON-OFF cell, which is a novel type of RGC not previously described in the rabbit retina. Chapter 2 characterizes the spiking properties and synaptic inputs to the UDs, which respond to changes in the visual scene by decreasing their firing, unlike all other types of RGCs. UDs are encountered rarely and the synaptic mechanisms underlying their unusual responses have not been investigated previously. Patch-clamp recordings from UDs show that the maintained firing arises within complex spikes, which are not produced by any other type of RGC. Both ON and OFF stimuli elicit only inhibitory synaptic input, mediated largely by glycinergic amacrine cells, the immediate effect of which is to transiently suppress the maintained firing. Glycinergic inhibition also alters the properties of the complex spikes by reactivation of Na+ channels. Chapter 3 characterizes the dendritic morphology and tracer-coupling pattern of UDs filled with Neurobiotin. The UDs have a distinctive bistratified morphology, branching in stratum 1 (s1) and s4/5 of the inner plexiform layer, largely outside the cholinergic strata, with dendrites that dive retroflexively from s1 back into s4/5. UDs are tracer coupled to neighboring RGCs and are estimated to account for ~2% of the RGCs in the visual streak of the rabbit retina. UDs show tracer coupling to a type of GABAergic amacrine cell that co-stratifies with the dendrites of the UDs in s4/5. Chapter 4 examines how the synaptic inputs shape the velocity tuning of DSGCs, which comprise two main types that can be readily distinguished both morphologically and physiologically. The well characterized ON-OFF DSGCs respond to a broad range of image velocities, whereas the less common ON DSGCs are tuned to slower image velocities. The synaptic mechanisms underlying the generation of direction selectivity appear to be similar in both types in that preferred-direction image motion elicits a greater excitatory input and null-direction image motion elicits a greater inhibitory input. To examine the temporal tuning of the DSGCs, the cells were stimulated either with a grating drifted over the receptive-field center at a range of velocities or with a light spot flickered at different temporal frequencies. Whereas the excitatory and inhibitory inputs to the ON-OFF DSGCs are relatively constant over a wide range of temporal frequencies, the ON DSGCs receive less excitation and more inhibition at higher temporal frequencies. Moreover, transient inhibition precedes sustained excitation in the ON DSGCs, leading to slowly activating, sustained spike responses. Consequently, at higher temporal frequencies, weaker excitation combines with fast-rising inhibition resulting in lower spike output. Chapter 5 establishes that the ON DSGCs actually comprise two distinct types of RGCs. While both types show robust direction-selectivity, one type responds to ON stimuli with sustained firing whereas the other type responds with transient firing. The two types also have quite distinct dendritic morphologies: the sustained ON DSGCs have shorter and more numerous terminal dendrites distributed throughout the dendritic field. In addition, the transient ON DSGCs, but not the sustained ON DSGCs, show tracer coupling to a population of amacrine cells when filled with Neurobiotin. Both types have been encountered in previous studies but it was not recognized that they are distinct types. Chapter 6 characterizes a novel type of RGC that gives transient responses at light ON and light OFF and is non-directional. It can therefore be distinguished from other types of ON-OFF RGCs, including the DSGCs (which are directional) and the local-edge-detectors (which are sustained). The OFF receptive field of these ‘transient ON-OFF’ cells is narrower than the ON receptive field, whereas the converse is true for the local edge detectors. The spike responses of the cells are largely shaped by the excitatory inputs because direct inhibitory inputs are mainly recruited by stimuli that are larger than the dendritic field. Dye injection reveals that the transient ON-OFF cell has a bistratified morphology, branching between the cholinergic strata in s2 and s3/4. This type of bistratified ON-OFF RGC does not appear to have been identified in previous physiological and morphological catalogs of rabbit RGCs