Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex

Oded Klavir; Matthias Prigge; Ayelet Sarel; Rony Paz; Ofer Yizhar

doi:10.1038/nn.4523

Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex

Oded Klavir, Matthias Prigge, Ayelet Sarel, Rony Paz, Ofer Yizhar

Research output: Contribution to journal › Article › peer-review

Abstract

Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA-mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.

Original language	English
Pages (from-to)	836-844
Number of pages	9
Journal	Nature Neuroscience
Volume	20
Issue number	6
DOIs	https://doi.org/10.1038/nn.4523
State	Published - 1 Jun 2017
Externally published	Yes

Bibliographical note

Funding Information:
We thank R. Levy for help with viral vector production and R. Zwang for help with cloning. We thank I. Goshen, Y. Ziv and all Yizhar lab members for discussions and critical reading of the manuscript. This work was supported in part by grants to O.Y. from the Israel Ministry of Science Technology and Space, the Israel Science Foundation (ISF #1351-12), FP7 grants StG #337637 and CIG #321919, and the Human Frontier Science Program. R.P.'s contribution was supported by ISF #26613, Minerva and ERC-FP7-StG 281171. O.Y. is supported by the Gertrude and Philip Nollman Career Development Chair. M.P. was supported by a Minerva postdoctoral fellowship. Work in the Yizhar lab is supported by the Adelis Foundation, the Grodetsky Center for Higher Brain Functions, Jean-Charles Schwartz and Marc-Antoine Schwartz, the Appleton Family Trust and the Lord Sieff Brimpton Memorial Fund.

Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

ASJC Scopus subject areas

Neuroscience (all)

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10.1038/nn.4523

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abstract = "Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA-mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.",

author = "Oded Klavir and Matthias Prigge and Ayelet Sarel and Rony Paz and Ofer Yizhar",

note = "Funding Information: We thank R. Levy for help with viral vector production and R. Zwang for help with cloning. We thank I. Goshen, Y. Ziv and all Yizhar lab members for discussions and critical reading of the manuscript. This work was supported in part by grants to O.Y. from the Israel Ministry of Science Technology and Space, the Israel Science Foundation (ISF #1351-12), FP7 grants StG #337637 and CIG #321919, and the Human Frontier Science Program. R.P.'s contribution was supported by ISF #26613, Minerva and ERC-FP7-StG 281171. O.Y. is supported by the Gertrude and Philip Nollman Career Development Chair. M.P. was supported by a Minerva postdoctoral fellowship. Work in the Yizhar lab is supported by the Adelis Foundation, the Grodetsky Center for Higher Brain Functions, Jean-Charles Schwartz and Marc-Antoine Schwartz, the Appleton Family Trust and the Lord Sieff Brimpton Memorial Fund. Publisher Copyright: {\textcopyright} 2017 Nature America, Inc., part of Springer Nature. All rights reserved.",

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Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex

Abstract

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