M.Sc Thesis


M.Sc StudentPrendes Milagros
SubjectIn Vivo Calcium Imaging of Neuronal Responses to Ultrasonic
Retinal Stimulation
DepartmentDepartment of Biomedical Engineering
Supervisors PROFESSOR EMERITUS Eitan Kimmel
PROF. Shy Shoham
Full Thesis textFull thesis text - English Version


Abstract

Degenerative diseases of the outer retina, a leading cause of visual loss, are characterized by photoreceptor degeneration. Among these diseases, the most common are age-related macular degeneration and retinitis pigmentosa. In these retinal dystrophies, most of the inner retinal neurons are preserved and still capable to produce a response. Because of this, artificial stimulation of the surviving cells is one of the most promising approaches towards vision restoration in patients suffering from these ailments.

Ultrasonic neuromodulation is an emerging method that has gained importance in neuroscience and neural engineering applications. Low-intensity ultrasound (US) has been shown to modulate activity in excitable tissue by mechanical interactions between the US wave and the cell membrane.

Here, we focused on studying the effects of US waves on the generation of action potential (AP) in mice neurons and the direct visualization of responses to US. For this, transfected and transgenic mice expressing neural calcium indicators GCaMP6s, GCaMP6f and jRCaMP1a were recorded under US stimulation. We first demonstrated retinal neurons responsiveness using light stimulation, which evoked robust and fast retinal neuron activity. Later, we examined cell responses to different US stimulation profiles in complete absence of light. The effects of different US parameters were compared considering the RMS of the responses. Retinal neurons showed the highest RMS for the strongest US intensity and the highest pulse repetition frequency. The activity dynamics of US responses were comparable to that of light stimulation.

This research contributes to future investigations of US wave interaction with retinal neurons shedding light on a non-invasive approach for vision restoration.