Optogenetic stimulation of the cochlear nucleus using channelrhodopsin-2 evokes activity in the central auditory pathways

Brain Res. 2015 Mar 2;1599:44-56. doi: 10.1016/j.brainres.2014.11.044. Epub 2014 Dec 3.

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.

Keywords: Auditory cortex; ChR2; Inferior colliculus; Neural prosthesis; Synchronization index.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Action Potentials
  • Animals
  • Auditory Cortex / cytology
  • Auditory Cortex / physiology
  • Auditory Pathways / cytology
  • Auditory Pathways / physiology*
  • Channelrhodopsins
  • Cochlear Nucleus / cytology
  • Cochlear Nucleus / physiology*
  • Electric Stimulation
  • Evoked Potentials, Auditory, Brain Stem
  • Feasibility Studies
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Inferior Colliculi / cytology
  • Inferior Colliculi / physiology
  • Mice, Inbred CBA
  • Neurons / cytology
  • Neurons / physiology
  • Optogenetics / methods*
  • Photic Stimulation

Substances

  • Channelrhodopsins
  • Green Fluorescent Proteins