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Molecular Neurobiology

, Volume 56, Issue 7, pp 4855–4865 | Cite as

Optogenetic Long-Term Depression Induction in the PVT-CeL Circuitry Mediates Decreased Fear Memory

  • Ming Chen
  • Lin-lin BiEmail author
Article

Abstract

The dysregulation of fear learning and abnormal activities of cerebral networks may contribute to the etiologies of anxiety disorders. Although it has been proposed that decreased activity in the paraventricular nucleus of the thalamus (PVT) to the lateral central nucleus of amygdala (CeL) pathway could induce an attenuation of learned fear, no study has shown the effect of the direct optogenetic activation of PVT projecting CeL neurons in vivo on unconditioned fear-related behaviors or learned fear expression. The mechanisms that control the neuronal activity of the PVT-CeL pathway involved in anxiety are rare. Here, we found that CeL neurons have varied responses to optogenetic excitation of PVT terminals in the CeL: neurons with relative high excitability(~ 30%), neurons with relative low excitability(~ 60%), and neurons with no excitability (~ 10%). We next explored the role of the PVT-CeL pathway in unconditioned and conditioned fear-related behaviors by using optogenetics and anxiety assays in freely moving mice. We observed that temporally precise optogenetic activation of the CeL-projecting PVT neurons had no effect on unconditioned fear-related behaviors on the elevated plus maze test and the open field test. But optogenetic activation of the CeL-projecting PVT neurons increased conditioned fear expression. We then found that optogenetic long-term depression (LTD) induction in the CeL receiving PVT afferents effectively exerted a persistent attenuation of learned fear. The percentage of neurons with relative high excitability was decreased by the LTD induction, and the percentage of neurons with relative low excitability was increased by the LTD induction. Taking these results together, we identify that increased activity of the PVT-CeL pathway could lead to as excessive learned fear. The CeL neurons with relative high responses to the photo-stimulation of PVT afferents in the CeL may be the key neurons that regulate the output of learned fear expression. Our optogenetic LTD protocol may inspire the development of novel treatments for anxiety disorders involving deep brain stimulation to induce plasticity at relevant brain areas.

Keywords

The PVT-CeL circuitry Optogenetics LTD Fear memory 

Notes

Acknowledgments

We thank Shu-yuan Xiao and Hong-lei Chen for their constructive suggestions on the paper design and writing.

Funding Information

This work was partly supported by grants from the National Natural Science Foundation of China (31600970, 81200119), the funds for Luojia Young Scholars of Wuhan University (for Lin-lin Bi), and the fund for Hubei Province Natural Science Foundation (2018CFB475).

Supplementary material

12035_2018_1407_MOESM1_ESM.doc (2.3 mb)
ESM 1 (DOC 2322 kb)

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Authors and Affiliations

  1. 1.Department of Pathology, School of Basic Medical SciencesWuhan UniversityWuhanChina
  2. 2.Department of CardiologyZhongnan Hospital of Wuhan UniversityWuhanChina
  3. 3.Wuhan University Center for Pathology and Molecular DiagnosticsZhongnan Hospital of Wuhan UniversityWuhanChina

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