Yuka Okazaki

Parameters of optic nerve electrical stimulation affecting neuroprotection of axotomized retinal ganglion cells in adult rats

We previously showed the enhancement of survival of retinal ganglion cells (RGCs) by electrical stimulation (ES) of the optic nerve (ON) stump in adult rats. To elucidate the mechanisms underlying the survival enhancement, we determined whether the neuroprotective effect of ES is affected by the following parameters: stimulation time, frequency of current pulses and starting of ES. ES for 10min immediately after ON transection was not effective in increasing the number of surviving RGCs 7 days after the transection, but that for 30min was effective. ES at 20Hz was the most effective, when applied just after axotomy. When the starting of ES to the ON was shifted either 3h after or 4h before the axotomy, the neuroprotective effect of ES was not observed. These results suggest that the electrical activation of RGCs and/or the transected ON interfere with early events after axotomy that leads to RGC death.

In Vivo Voltage-Sensitive Dye Study of Lateral Spreading of Cortical Activity in Mouse Primary Visual Cortex Induced by a Current Impulse

In the mammalian primary visual cortex (V1), lateral spreading of excitatory potentials is believed to be involved in spatial integrative functions, but the underlying cortical mechanism is not well understood. Visually-evoked population-level responses have been shown to propagate beyond the V1 initial activation site in mouse, similar to higher mammals. Visually-evoked responses are, however, affected by neuronal circuits prior to V1 (retina, LGN), making the separate analysis of V1 difficult. Intracortical stimulation eliminates these initial processing steps. We used in vivo RH1691 voltage-sensitive dye (VSD) imaging and intracortical microstimulation in adult C57BL/6 mice to elucidate the spatiotemporal properties of population-level signal spreading in V1 cortical circuits. The evoked response was qualitatively similar to that measured in single-cell electrophysiological experiments in rodents: a fast transient fluorescence peak followed by a fast and a slow decrease or hyperpolarization, similar to EPSP and fast and slow IPSPs in single cells. The early cortical response expanded at speeds commensurate with long horizontal projections (at 5% of the peak maximum, 0.08–0.15 m/s) however, the bulk of the VSD signal propagated slowly (at half-peak maximum, 0.05–0.08 m/s) suggesting an important role of regenerative multisynaptic transmission through short horizontal connections in V1 spatial integrative functions. We also found a tendency for a widespread and fast cortical response suppression in V1, which was eliminated by GABAA-antagonists gabazine and bicuculline methiodide. Our results help understand the neuronal circuitry involved in lateral spreading in V1.

Voltage-sensitive dye imaging of the visual cortices responding to electrical pulses at different intervals in mice in vivo

Properties of the neural responses to electrical stimulus pulses delivered at various inter-pulse intervals were examined in the visual cortices of mice in vivo, with utilizing the voltage-sensitive dye imaging technique. Our experimental results provided the relationships between the inter-pulse intervals and the stimulus-evoked transient depolarizations, which may offer insight into the design of effective and efficient stimulation for cortical visual prostheses.

Survival-Promoting Effect of Electrical Stimulation on Axotomized Retinal Ganglion Cells

It has been well established that axotomized retinal ganglion cells (RGCs) of adult mammals can survive and regenerate their axons when the peripheral nerve is autografted [1]. However, the number of RGCs with regenerated axons is still limited. One major reason for poor regeneration is that many RGCs degenerate shortly after optic nerve (ON) transection. For example, half of the rat RGCs were lost within 1 week after intraorbital ON transection, and only 10% survived 2 weeks after axotomy [2]. The rescue of axotomized RGCs from such early retrograde degeneration is a prerequisite for the functional recovery of vision against ON damage.