Hearing the light: Optogenetic Stimulation of the Auditory Nerve
Event details
| Date | 05.04.2017 |
| Hour | 11:00 › 12:00 |
| Speaker | Prof. Tobias Moser, University of Göttingen Medical Center, Germany. |
| Location | |
| Category | Conferences - Seminars |
DISTINGUISHED LECTURES in NEUROPROSTHETICS
Abstract
When hearing fails, speech comprehension can be restored by auditory prostheses. However, sound coding with current prostheses, based on electrical stimulation of auditory neurons, has limited frequency resolution due to broad current spread. We aim to improve frequency and intensity resolution of cochlear implant coding by establishing spatially confined optical stimulation of spiral ganglion neurons (SGNs). We have established optogenetic stimulation of the auditory pathway in rodents using virus-mediated expression of channelrhodopsins to render SGNs light-sensitive. Optogenetic stimulation of spiral ganglion neurons activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses at various stages of the auditory system. Fast opsins enabled SGN firing at physiological rates (hundreds per second). We approximated the spatial spread of cochlear excitation by recording local field potentials in the inferior colliculus in response to suprathreshold optical and electrical stimuli, which suggested a better frequency resolution for optogenetic than for electrical stimulation.
Towards characterizing the percept induced by cochlear optogenetics we studied activation of neurons in primary auditory cortex and performed a behavioral analysis in virus-injected gerbils. Various types of optogenetic responses were observed in auditory cortex. For the behavioral analysis we implanted an optical fiber into the round window of the injected cochlea. Subsequently, animals were trained in a detection task using the shuttle box paradigm. In parallel, optically driven auditory brainstem responses (oABRs) were measured during the period of behavioral testing to monitor the physiological response to optical stimulation of SGNs. We found that amplitudes, latencies and thresholds of oABRs stayed stable for a period of at least 3 weeks. During this period gerbils learned to avoid electric aversive stimuli cued by optical SGN stimulation within a few days and obtained response rates of up to 95%. Behavioral thresholds of light amplitude were found to be below physiological thresholds (< 3mW, close to the threshold of the neurons in auditory cortex) and thresholds of light pulse duration were as short as 0.1ms. This study demonstrates that stimulation of channelrhodopsin-expressing spiral ganglion neurons with blue light creates both a stable physiological response and a robust auditory percept over several weeks. In summary, optogenetic stimulation of the auditory nerve is feasible and bears substantial potential for future application in research and hearing restoration.
Bio
Tobias Moser is a professor at University of Göttingen Medical Center where he directs the Institute of Auditory Neuroscience. He also is heading research groups at the German Primate Center and at Max-Planck-Institutes in Göttingen. His work focuses on the molecular anatomy, physiology and pathophysiology of sound encoding and information processing in the auditory system as well as the restoration of hearing by gene replacement therapy and optogenetic stimulation. His team combines various techniques to characterize synapses of hair cells and the auditory brainstem from the molecular to the systems level. This way they have contributed to the understanding of structure and function of auditory synapses and initiated the concept of auditory synaptopathy. Towards restoration of hearing Moser's team aims to establish virus-mediated gene replacement therapy of auditory synaptopathy and pursue the optogenetic stimulation of auditory nerve for improving the performance of the cochlear implant.
Abstract
When hearing fails, speech comprehension can be restored by auditory prostheses. However, sound coding with current prostheses, based on electrical stimulation of auditory neurons, has limited frequency resolution due to broad current spread. We aim to improve frequency and intensity resolution of cochlear implant coding by establishing spatially confined optical stimulation of spiral ganglion neurons (SGNs). We have established optogenetic stimulation of the auditory pathway in rodents using virus-mediated expression of channelrhodopsins to render SGNs light-sensitive. Optogenetic stimulation of spiral ganglion neurons activated the auditory pathway, as demonstrated by recordings of single neuron and neuronal population responses at various stages of the auditory system. Fast opsins enabled SGN firing at physiological rates (hundreds per second). We approximated the spatial spread of cochlear excitation by recording local field potentials in the inferior colliculus in response to suprathreshold optical and electrical stimuli, which suggested a better frequency resolution for optogenetic than for electrical stimulation.
Towards characterizing the percept induced by cochlear optogenetics we studied activation of neurons in primary auditory cortex and performed a behavioral analysis in virus-injected gerbils. Various types of optogenetic responses were observed in auditory cortex. For the behavioral analysis we implanted an optical fiber into the round window of the injected cochlea. Subsequently, animals were trained in a detection task using the shuttle box paradigm. In parallel, optically driven auditory brainstem responses (oABRs) were measured during the period of behavioral testing to monitor the physiological response to optical stimulation of SGNs. We found that amplitudes, latencies and thresholds of oABRs stayed stable for a period of at least 3 weeks. During this period gerbils learned to avoid electric aversive stimuli cued by optical SGN stimulation within a few days and obtained response rates of up to 95%. Behavioral thresholds of light amplitude were found to be below physiological thresholds (< 3mW, close to the threshold of the neurons in auditory cortex) and thresholds of light pulse duration were as short as 0.1ms. This study demonstrates that stimulation of channelrhodopsin-expressing spiral ganglion neurons with blue light creates both a stable physiological response and a robust auditory percept over several weeks. In summary, optogenetic stimulation of the auditory nerve is feasible and bears substantial potential for future application in research and hearing restoration.
Bio
Tobias Moser is a professor at University of Göttingen Medical Center where he directs the Institute of Auditory Neuroscience. He also is heading research groups at the German Primate Center and at Max-Planck-Institutes in Göttingen. His work focuses on the molecular anatomy, physiology and pathophysiology of sound encoding and information processing in the auditory system as well as the restoration of hearing by gene replacement therapy and optogenetic stimulation. His team combines various techniques to characterize synapses of hair cells and the auditory brainstem from the molecular to the systems level. This way they have contributed to the understanding of structure and function of auditory synapses and initiated the concept of auditory synaptopathy. Towards restoration of hearing Moser's team aims to establish virus-mediated gene replacement therapy of auditory synaptopathy and pursue the optogenetic stimulation of auditory nerve for improving the performance of the cochlear implant.
Practical information
- Informed public
- Free
Organizer
- Distinguished Lectures in Neuroprosthetics, http://cnp.epfl.ch/seminars
Contact
- Host; Prof S. Micera