Synaptic Origins of the Complex Receptive Field Structure in Primate Smooth Monostratified Retinal Ganglion Cells.

Considerable progress has been made in studying the receptive fields of the most common primate retinal ganglion cell (RGC) types, such as parasol RGCs. Much less is known about the rarer primate RGC types and the circuitry that gives rise to noncanonical receptive field structures. The goal of this study was to analyze synaptic inputs to smooth monostratified RGCs to determine the origins of their complex spatial receptive fields, which contain isolated regions of high sensitivity called "hotspots." Interestingly, smooth monostratified RGCs co-stratify with the well-studied parasol RGCs and are thus constrained to receiving input from bipolar and amacrine cells with processes sharing the same layer, raising the question of how their functional differences originate. Through 3D reconstructions of circuitry and synapses onto ON smooth monostratified and ON parasol RGCs from central macaque retina, we identified four distinct sampling strategies employed by smooth and parasol RGCs to extract diverse response properties from co-stratifying bipolar and amacrine cells. The two RGC types differed in the proportion of amacrine cell input, relative contributions of co-stratifying bipolar cell types, amount of synaptic input per bipolar cell, and spatial distribution of bipolar cell synapses. Our results indicate that the smooth RGC's complex receptive field structure arises through spatial asymmetries in excitatory bipolar cell input which formed several discrete clusters comparable with physiologically measured hotspots. Taken together, our results demonstrate how the striking differences between ON parasol and ON smooth monostratified RGCs arise from distinct strategies for sampling a common set of synaptic inputs.

Synaptic inputs to displaced intrinsically-photosensitive ganglion cells in macaque retina.

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified. The ipRGCs with somas in the ganglion cell layer have been studied extensively, but less is known about those with somas in the inner nuclear layer, the "displaced" cells. To investigate their synaptic inputs, three sets of horizontal, ultrathin sections through central macaque retina were collected using serial block-face scanning electron microscopy. One displaced ipRGC received nearly all of its excitatory inputs from ON bipolar cells and would therefore be expected to have ON responses to light. In each of the three volumes, there was also at least one cell that had a large soma in the inner nuclear layer, varicose axons and dendrites with a large diameter that formed large, extremely sparse arbor in the outermost stratum of the inner plexiform layer. They were identified as the displaced M1 type of ipRGCs based on this morphology and on the high density of granules in their somas. They received extensive input from amacrine cells, including the dopaminergic type. The vast majority of their excitatory inputs were from OFF bipolar cells, including two subtypes with extensive input from the primary rod pathway. They would be expected to have OFF responses to light stimuli below the threshold for melanopsin or soon after the offset of a light stimulus.

Conserved circuits for direction selectivity in the primate retina.

The detection of motion direction is a fundamental visual function and a classic model for neural computation. In the non-primate retina, direction selectivity arises in starburst amacrine cell (SAC) dendrites, which provide selective inhibition to direction-selective retinal ganglion cells (dsRGCs). Although SACs are present in primates, their connectivity and the existence of dsRGCs remain open questions. Here, we present a connectomic reconstruction of the primate ON SAC circuit from a serial electron microscopy volume of the macaque central retina. We show that the structural basis for the SACs' ability to confer directional selectivity on postsynaptic neurons is conserved. SACs selectively target a candidate homolog to the mammalian ON-sustained dsRGCs that project to the accessory optic system (AOS) and contribute to gaze-stabilizing reflexes. These results indicate that the capacity to compute motion direction is present in the retina, which is earlier in the primate visual system than classically thought.

Synaptic inputs to broad thorny ganglion cells in macaque retina.

In primates, broad thorny retinal ganglion cells are highly sensitive to small, moving stimuli. They have tortuous, fine dendrites with many short, spine-like branches that occupy three contiguous strata in the middle of the inner plexiform layer. The neural circuits that generate their responses to moving stimuli are not well-understood, and that was the goal of this study. A connectome from central macaque retina was generated by serial block-face scanning electron microscopy, a broad thorny cell was reconstructed, and its synaptic inputs were analyzed. It received fewer than 2% of its inputs from both ON and OFF types of bipolar cells; the vast majority of its inputs were from amacrine cells. The presynaptic amacrine cells were reconstructed, and seven types were identified based on their characteristic morphology. Two types of narrow-field cells, knotty bistratified Type 1 and wavy multistratified Type 2, were identified. Two types of medium-field amacrine cells, ON starburst and spiny, were also presynaptic to the broad thorny cell. Three types of wide-field amacrine cells, wiry Type 2, stellate wavy, and semilunar Type 2, also made synapses onto the broad thorny cell. Physiological experiments using a macaque retinal preparation in vitro confirmed that broad thorny cells received robust excitatory input from both the ON and the OFF pathways. Given the paucity of bipolar cell inputs, it is likely that amacrine cells provided much of the excitatory input, in addition to inhibitory input.

Another Blue-ON ganglion cell in the primate retina.

A classic and highly influential model of visual processing proposes that the role of the retina is to compress visual information for optimal transmission to the brain [1]. Drawing on ideas from information theory, an efficient retinal code could be defined as one that reduces redundancy to communicate as much information as possible, given the optic nerve's limited capacity. From this redundancy reduction hypothesis, a theory of retinal color coding emerged in which the three most common retinal ganglion cell (RGC) types captured much of the variance in natural spectra [2]. Within this compact code, the 'Blue-ON' small bistratified RGC was thought to be the only pathway necessary for comparing short (S) wavelength-sensitive cones to long (L) and medium (M) wavelength-sensitive cones [3,4]. Here, we discovered a new wide-field RGC type receiving the same cone-opponent input as the small bistratified RGC, indicating that there is more redundancy in the retinal color code than previously appreciated.