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High-fidelity optical excitation of cortico-cortical projections at physiological frequencies.

Publication ,  Journal Article
Hass, CA; Glickfeld, LL
Published in: J Neurophysiol
November 1, 2016

Optogenetic activation of axons is a powerful approach for determining the synaptic properties and impact of long-range projections both in vivo and in vitro. However, because of the difficulty of measuring activity in axons, our knowledge of the reliability of optogenetic axonal stimulation has relied on data from somatic recordings. Yet, there are many reasons why activation of axons may not be comparable to cell bodies. Thus we have developed an approach to more directly assess the fidelity of optogenetic activation of axonal projections. We expressed opsins (ChR2, Chronos, or oChIEF) in the mouse primary visual cortex (V1) and recorded extracellular, pharmacologically isolated presynaptic action potentials in response to axonal activation in the higher visual areas. Repetitive stimulation of axons with ChR2 resulted in a 70% reduction in the fiber volley amplitude and a 60% increase in the latency at all frequencies tested (10-40 Hz). Thus ChR2 cannot reliably recruit axons during repetitive stimulation, even at frequencies that are reliable for somatic stimulation, likely due to pronounced channel inactivation at the high light powers required to evoke action potentials. By comparison, oChIEF and Chronos evoked photocurrents that inactivated minimally and could produce reliable axon stimulation at frequencies up to 60 Hz. Our approach provides a more direct and accurate evaluation of the efficacy of new optogenetic tools and has identified Chronos and oChIEF as viable tools to interrogate the synaptic and circuit function of long-range projections.

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Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

November 1, 2016

Volume

116

Issue

5

Start / End Page

2056 / 2066

Location

United States

Related Subject Headings

  • Visual Pathways
  • Visual Cortex
  • Organ Culture Techniques
  • Optogenetics
  • Neurology & Neurosurgery
  • Mice
  • Female
  • Channelrhodopsins
  • Animals
  • Action Potentials
 

Citation

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Hass, C. A., & Glickfeld, L. L. (2016). High-fidelity optical excitation of cortico-cortical projections at physiological frequencies. J Neurophysiol, 116(5), 2056–2066. https://doi.org/10.1152/jn.00456.2016
Hass, Charles A., and Lindsey L. Glickfeld. “High-fidelity optical excitation of cortico-cortical projections at physiological frequencies.J Neurophysiol 116, no. 5 (November 1, 2016): 2056–66. https://doi.org/10.1152/jn.00456.2016.
Hass CA, Glickfeld LL. High-fidelity optical excitation of cortico-cortical projections at physiological frequencies. J Neurophysiol. 2016 Nov 1;116(5):2056–66.
Hass, Charles A., and Lindsey L. Glickfeld. “High-fidelity optical excitation of cortico-cortical projections at physiological frequencies.J Neurophysiol, vol. 116, no. 5, Nov. 2016, pp. 2056–66. Pubmed, doi:10.1152/jn.00456.2016.
Hass CA, Glickfeld LL. High-fidelity optical excitation of cortico-cortical projections at physiological frequencies. J Neurophysiol. 2016 Nov 1;116(5):2056–2066.

Published In

J Neurophysiol

DOI

EISSN

1522-1598

Publication Date

November 1, 2016

Volume

116

Issue

5

Start / End Page

2056 / 2066

Location

United States

Related Subject Headings

  • Visual Pathways
  • Visual Cortex
  • Organ Culture Techniques
  • Optogenetics
  • Neurology & Neurosurgery
  • Mice
  • Female
  • Channelrhodopsins
  • Animals
  • Action Potentials