Precise multimodal optical control of neural ensemble activity

Nat Neurosci. 2018 Jun;21(6):881-893. doi: 10.1038/s41593-018-0139-8. Epub 2018 Apr 30.

Abstract

Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 × 550 × 100-µm3 volume of brain tissue. This approach allows the synthesis and editing of complex neural activity patterns needed to gain insight into the principles of neural codes.

Publication types

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

MeSH terms

  • Animals
  • Brain / physiology*
  • Cell Survival / physiology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology
  • Electrophysiological Phenomena
  • Female
  • Holography / methods*
  • Mice
  • Mice, Inbred ICR
  • Mice, Transgenic
  • Nerve Net / physiology*
  • Neurons / physiology*
  • Opsins / pharmacology
  • Optogenetics
  • Patch-Clamp Techniques
  • Photic Stimulation / methods*
  • Pregnancy

Substances

  • Opsins