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Currently, a challenge in electrical stimulation of the retina with a visual prosthesis (bionic eye) is to excite only the cells lying directly under the electrode in the ganglion cell layer, while avoiding excitation of axon bundles that pass over the surface of the retina in the nerve fiber layer. Stimulation of overlying axons results in irregular visual percepts, limiting perceptual efficacy. This research explores how differences in fiber orientation between the nerve fiber layer and ganglion cell layer leads to differences in the electrical activation of the axon initial segment and axons of passage. Approach. Axons of passage of retinal ganglion cells in the nerve fiber layer are characterized by a narrow distribution of fiber orientations, causing highly anisotropic spread of applied current. In contrast, proximal axons in the ganglion cell layer have a wider distribution of orientations. A four-layer computational model of epiretinal extracellular stimulation that captures the effect of neurite orientation in anisotropic tissue has been developed using a volume conductor model known as the cellular composite model. Simulations are conducted to investigate the interaction of neural tissue orientation, stimulating electrode configuration, and stimulation pulse duration and amplitude. Main results. Our model shows that simultaneous stimulation with multiple electrodes aligned with the nerve fiber layer can be used to achieve selective activation of axon initial segments rather than passing fibers. This result can be achieved while reducing required stimulus charge density and with only modest increases in the spread of activation in the ganglion cell layer, and is shown to extend to the general case of arbitrary electrode array positioning and arbitrary target volume. Significance. These results elucidate a strategy for more targeted stimulation of retinal ganglion cells with experimentally-relevant multi-electrode geometries and achievable stimulation requirements. [ABSTRACT FROM AUTHOR]

A fundamental goal of neuroscience is to understand how cognitive processes, such as operant conditioning, are performed by the brain. Typical and well studied examples of operant conditioning, in which the firing rates of individual cortical neurons in monkeys are increased using rewards, provide an opportunity for insight into this. Studies of reward-modulated spike-timing-dependent plasticity (RSTDP), and of other models such as R-max, have reproduced this learning behavior, but they have assumed that no unsupervised learning is present (i.e., no learning occurs without, or independent of, rewards). We show that these models cannot elicit firing rate reinforcement while exhibiting both reward learning and ongoing, stable unsupervised learning. To fix this issue, we propose a new RSTDP model of synaptic plasticity based upon the observed effects that dopamine has on long-term potentiation and depression (LTP and LTD). We show, both analytically and through simulations, that our new model can exhibit unsupervised learning and lead to firing rate reinforcement. This requires that the strengthening of LTP by the reward signal is greater than the strengthening of LTD and that the reinforced neuron exhibits irregular firing. We show the robustness of our findings to spike-timing correlations, to the synaptic weight dependence that is assumed, and to changes in the mean reward. We also consider our model in the differential reinforcement of two nearby neurons. Our model aligns more strongly with experimental studies than previous models and makes testable predictions for future experiments. [ABSTRACT FROM AUTHOR]