The ability to register a reliable optical responses, in vivo, from retinal neurons within a tissue volume remains a matter of considerable debate. However, Cohen’s work was based on tissue analysed in vitro and relied on signals from large individual neurons. The contrast sensitivity of OCTs using broad spectral light sources is close to that required to detect neuronal light scattering, birefringence, and structural changes associated with action potentials as reported in pioneering work by Cohen 7, 8, 9, 10, 11. It is widely used for clinical diagnostic imaging of eye diseases 3, 4 and other structures of biomedical interest such as skin and colon where changes in tissue thickness can be quantified at near cellular resolution 5, 6. Optical Coherence Tomography (OCT) derives high resolution spatially distinct images from the interferometric analysis of tissues probed with low coherence laser light, similar to ultrasound 1, 2. While our data suggest that optical imaging of retinal activity is possible with high resolution OCT, the technical challenges are not trivial. We observed a close correlation between the patch optical responses and mean electrical activity of the visual neurons in afferent pathway. We hypothesise that these patches correspond to individual cells, or segments of blood vessels within the inner retina. Regions of interest were subdivided into three-dimensional patches (up to 5–15 μm in diameter) based on response similarity. We observed increases in contrast variability in the retinal ganglion cell layer and nerve fibre layer with flash stimuli and gratings. We imaged anaesthetised paralysed tree shrews, gated image acquisition, and used numerical filters to eliminate noise arising from retinal movements during respiratory and cardiac cycles. We report the first optical recording of neuronal excitation at cellular resolution in the inner retina by quantifying optically recorded stimulus-evoked responses from the retinal ganglion cell layer and comparing them with an electrophysiological standard. Low coherence laser interferometry has revolutionised quantitative biomedical imaging of optically transparent structures at cellular resolutions.
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