title: Hearing the light: neural and perceptual encoding of optogenetic stimulation in the central auditory pathway.
abstract: Optogenetics provides a means to dissect the organization and function of neural circuits. Optogenetics also offers the translational promise of restoring sensation, enabling movement or supplanting abnormal activity patterns in pathological brain circuits. However, the inherent sluggishness of evoked photocurrents in conventional channelrhodopsins has hampered the development of optoprostheses that adequately mimic the rate and timing of natural spike patterning. Here, we explore the feasibility and limitations of a central auditory optoprosthesis by photoactivating mouse auditory midbrain neurons that either express channelrhodopsin-2 (ChR2) or Chronos, a channelrhodopsin with ultra-fast channel kinetics. Chronos-mediated spike fidelity surpassed ChR2 and natural acoustic stimulation to support a superior code for the detection and discrimination of rapid pulse trains. Interestingly, this midbrain coding advantage did not translate to a perceptual advantage, as behavioral detection of midbrain activation was equivalent with both opsins. Auditory cortex recordings revealed that the precisely synchronized midbrain responses had been converted to a simplified rate code that was indistinguishable between opsins and less robust overall than acoustic stimulation. These findings demonstrate the temporal coding benefits that can be realized with next-generation channelrhodopsins, but also highlight the challenge of inducing variegated patterns of forebrain spiking activity that support adaptive perception and behavior.
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] Program in Speech Hearing Bioscience and Technology, Harvard Medical School (HMS), Boston MA 02115.
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Hight
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] New Pathway MD Program, HMS 02115.
authors.forename: Jenny X
authors.initials: JX
authors.lastname: Chen
authors.affiliation: 1] The MIT Media Laboratory, Synthetic Neurobiology Group, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA [2] Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Klapoetke
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] Department of Otology and Laryngology, HMS, Boston MA, 02114.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Hancock
authors.affiliation: 1] Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215 [2] Department of Biomedical Engineering, Boston University 02215.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Shinn-Cunningham
authors.affiliation: 1] The MIT Media Laboratory, Synthetic Neurobiology Group, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA [2] Department of Biological Engineering, MIT, Cambridge, Massachusetts, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] Department of Otology and Laryngology, HMS, Boston MA, 02114.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: 1] Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114 [2] Center for Computational Neuroscience and Neural Technology, Boston University, Boston, Massachusetts 02215 [3] Department of Otology and Laryngology, HMS, Boston MA, 02114.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Polley
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology*; D001522:Behavior, Animal; D000075402:Channelrhodopsins; D055724:Electrophysiological Phenomena; D006309:Hearing / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D009474:Neurons / Q000378:metabolism; D062308:Optogenetics; D018408:Patch-Clamp Techniques
chemical_list: D000075402:Channelrhodopsins