Optogenetics for optical stimulation of auditory neurons

Background

Cochlear implants electrically stimulate auditory neurons to convey auditory information to the brain. Although performance is good in quiet listening conditions it deteriorates severely in more challenging acoustic environments such as a noisy restaurant and does not allow the appreciation of music or the comprehension of tonal languages.

The basic limitation of cochlear implants is the spread of electrical current from the stimulating electrodes that results in broad neural activation. A fundamental change in how cochlear implants work is likely to be the only way to overcome this inherent limitation and provide the improvements in resolution needed to advance the next generation of bionic technology. Over the last few years optogenetic techniques have been used to successfully activate neurons in the mammalian nervous system using optical stimulation.

The technique involves introducing light sensitive ion channels in the membranes of target neurons via gene therapy. The use of an optical stimulus is advantageous over electrical stimulation as light can be focused (imagine a narrow beam of light from a laser pointer). In this project we will use optical stimulation to activate auditory neurons to determine if we can improve the resolution of auditory signals in the brain.

Our research

The success of optical stimulation of the cochlea relies on expression of light sensitive ion channels called channelrhodopsin in auditory neurons. We have extensive experience in cochlear gene therapy and have developed the necessary techniques in a number of previous projects. In world-first research we present convincing preliminary data showing that we can transfect auditory neurons in the adult mammalian cochlea with channelrhodopsin. Furthermore, we have transfected auditory neuron cultures with channelrhodopsin and demonstrated action potentials derived from low powered blue light. These studies are both essential for establishing the basic data for future clinical translation of the research.

We propose to complement this research with the use of channelrhodopsin transgenic mice to help ascertain whether optical stimulation can focus the stimulation of auditory neurons. Transgenic mice will be a valuable experimental tool as the light sensitive ion channel expression will be consistent between animals and will enable us to more accurately assess the spread of activation in the brain.

We will optically or electrically stimulate individual auditory neurons expressing channelrhodopsin and compare their functional responses and characteristics in vitro. We will also optically or electrically stimulate auditory neurons expressing channelrhodopsin in the cochlea and compare the spatial and temporal precision of activation using multichannel recording techniques in the brain in vivo.

Research team

Principal researchers: Dr Rachael Richardson, Dr Andrew Wise, A/Prof James Fallon

Collaborators: Prof Stephen O’Leary (University of Melbourne), Dr Karina Needham (University of Melbourne)

Funding

Action on Hearing Loss (UK), The Garnett Passe and Rodney Williams Memorial Foundation

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