title: Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways.
abstract: Optogenetics has become an important research tool and is being considered as the basis for several neural prostheses. However, few studies have applied optogenetics to the auditory brainstem. This study explored whether optical activation of the cochlear nucleus (CN) elicited responses in neurons in higher centers of the auditory pathway and whether it elicited an evoked response. Viral-mediated gene transfer was used to express channelrhodopsin-2 (ChR2) in the mouse CN. Blue light was delivered via an optical fiber placed near the surface of the infected CN and recordings were made in higher-level centers. Optical stimulation evoked excitatory multiunit spiking activity throughout the tonotopic axis of the central nucleus of the inferior colliculus (IC) and the auditory cortex (Actx). The pattern and magnitude of IC activity elicited by optical stimulation was comparable to that obtained with a 50dB SPL acoustic click. This broad pattern of activity was consistent with histological confirmation of green fluorescent protein (GFP) label of cell bodies and axons throughout the CN. Increasing pulse rates up to 320Hz did not significantly affect threshold or bandwidth of the IC responses, but rates higher than 50Hz resulted in desynchronized activity. Optical stimulation also evoked an auditory brainstem response, which had a simpler waveform than the response to acoustic stimulation. Control cases showed no responses to optical stimulation. These data suggest that optogenetic control of central auditory neurons is feasible, but opsins with faster channel kinetics may be necessary to convey information at rates typical of many auditory signals.
authors.affiliation: Department of Communication Sciences and Disorders, Worcester State University, Worcester, MA, USA; Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA.
authors.forename: Keith N
authors.initials: KN
authors.lastname: Darrow
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: Michaël C C
authors.initials: MC
authors.lastname: Slama
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA.
authors.forename: Elliott D
authors.initials: ED
authors.lastname: Kozin
authors.affiliation: Department of Communication Sciences and Disorders, Worcester State University, Worcester, MA, USA.
authors.forename: Maryanna
authors.initials: M
authors.lastname: Owoc
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hancock
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: Judith
authors.initials: J
authors.lastname: Kempfle
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: Albert
authors.initials: A
authors.lastname: Edge
authors.affiliation: Laboratory for Soft Bioelectronic Interfaces, Center for Neuroprosthetics, IMT/IBI, EPFL, Lausanne, Switzerland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lacour
authors.affiliation: Departments of Brain and Cognitive Sciences and Biological Engineering, MIT Media Lab and McGovern Institute, MIT, Cambridge, MA 02139, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Boyden
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: Daniel
authors.initials: D
authors.lastname: Polley
authors.affiliation: Eaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA, USA; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs.
authors.forename: M Christian
authors.initials: MC
authors.lastname: Brown
authors.affiliation: Department of Otology and Laryngology, Harvard Medical School, Boston, MA, USAs; Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, USA. Electronic address: Daniel_Lee@meei.harvard.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lee
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials; D000818:Animals; D001303:Auditory Cortex / Q000166:cytology / Q000502:physiology; D001306:Auditory Pathways / Q000166:cytology / Q000502:physiology*; D000075402:Channelrhodopsins; D017626:Cochlear Nucleus / Q000166:cytology / Q000502:physiology*; D004558:Electric Stimulation; D016057:Evoked Potentials, Auditory, Brain Stem; D005240:Feasibility Studies; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007245:Inferior Colliculi / Q000166:cytology / Q000502:physiology; D008808:Mice, Inbred CBA; D009474:Neurons / Q000166:cytology / Q000502:physiology; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation
chemical_list: D000075402:Channelrhodopsins; D049452:Green Fluorescent Proteins
keywords: Auditory cortex; ChR2; Inferior colliculus; Neural prosthesis; Synchronization index