Modeling the response of ON and OFF retinal bipolar cells during electric stimulation.

Retinal implants allowing blind people suffering from diseases like retinitis pigmentosa and macular degeneration to regain rudimentary vision are struggling with several obstacles. One of the main problems during external electric stimulation is the co-activation of the ON and OFF pathways which results in mutual impairment. In this study the response of ON and OFF cone retinal bipolar cells during extracellular electric stimulation from the subretinal space was examined. To gain deeper insight into the behavior of these cells sustained L-type and transient T-type calcium channels were integrated in the synaptic terminals of reconstructed 3D morphologies of ON and OFF cone bipolar cells. Intracellular calcium concentration in the synaptic regions of the model neurons was investigated as well since calcium influx is a crucial parameter for cell-to-cell activity between bipolar cells and retinal ganglion cells. It was shown that monophasic stimulation results in significant different calcium concentrations in the synaptic terminals of ON and OFF bipolar cells. Intracellular calcium increased to values up to fourfold higher in the OFF bipolar model neuron in comparison to the ON bipolar cell. Furthermore, geometric properties strongly influence the activation of bipolar cells. Monophasic, biphasic, single and repetitive pulses with similar lengths, amplitudes and polarities were applied to the two model neurons.

The oxygenation response to functional stimulation: is there a physiological meaning to the lag between parameters?

To investigate the regulation of the hemodynamic response to functional stimulation, functional near-infrared spectroscopy (fNIRS) has been used, due to its ability to assess the dynamics of oxygenated, deoxygenated and total hemoglobin concentration ([oxy-Hb], [deoxy-Hb] and [tot-Hb]). Concerning the latency of these parameters, recent studies have returned a consistent picture when comparing the oxygenation response in the sensorimotor to the visual system: changes in [oxy-Hb] lead those in [deoxy-Hb] by 1.6+/-0.2 s (mean+/-SD) for the sensorimotor system but not for the visual system (0.1+/-0.3 s). A number of physiological differences between these cortical areas may account for such a discrepancy, however, the methodological properties of transcranial NIRS also have a relevant influence. Here we show that for the motor system the latency between changes in oxy- compared to deoxy-Hb vanishes once efforts are made to reduce the effects of a systemic response accompanying sensorimotor activity. We apply two independent approaches to reduce the systemic response and find a simultaneous change in [oxy-Hb] and [deoxy-Hb] even in response to a motor paradigm. The two approaches are: (i) an experimental paradigm with alternating contralateral and ipsilateral motor performance without interspersed rest periods designed to minimize systemic changes and (ii) a global correction scheme in an experiment, comparing a unilateral motor performance to rest. These data shed some doubt on the alleged fundamental physiological difference between cortical hemodynamic regulation in motor and visual cortex and highlight the relevance to respect contributions of the systemic hemodynamics.