Another study on retina (macaque) using HDMEAs revealed the identification of the type, location, and strength of the functional input of each cone photoreceptor to each RGC (Field et al., 2010). Populations of midget, parasol, and small bistratified RGCs were recorded simultaneously in the presence of white noise “visual” stimulation. The spatial receptive field and response time of RGCs were detected by computing the spike-triggered average of the stimuli. Afterwards, the detected clusters of cells obtained by PCA were further stimulated with 10-fold smaller pixels (5 × 5 μm2) to reveal finer details of the receptive fields. The method was able to map putative cones accumulated across the receptive field of RGCs, which were verified by overlaying a microscopy image of cones labeled with peanut agglutinin (see Figure 11F). The authors were able to quantify the strength of connectivity between different RGC types and different types of cones (sensitive to red, green, or blue). These exhibit the capability of HDMEAs, combined with advanced stimulation and analysis techniques, to resolve the functional connectivity of neurons in the retina at single-cell resolution.
