Acute pharmacogenetic activation of medial prefrontal cortex excitatory neurons regulates anxiety-like behaviour

Sthitapranjya Pati, Ankit Sood, Sourish Mukhopadhyay, Vidita A. Vaidya

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

The medial prefrontal cortex (mPFC) is implicated in anxiety-like behaviour. In rodent models, perturbations of mPFC neuronal activity through pharmacological manipulations, optogenetic activation of mPFC neurons or cell-type specific pharmacogenetic inhibition of somatostatin interneurons indicate conflicting effects on anxiety-like behaviour. In the present study we examined the effects of pharmacogenetic activation of Ca2+/calmodulin-dependent protein kinase α (CamKIIα)-positive excitatory neurons on anxiety-like behaviour. We used clozapine-N-oxide (CNO) to pharmacogenetically activate virally delivered CamKIIα-hM3Dq-DREADD in mPFC excitatory neurons. The effects of acute CNO or vehicle treatment on anxiety-like behaviour in the open field and elevated plus maze tests were examined in rats virally infected with either CamKIIα-hM3Dq-DREADD or CamKIIα-GFP. In addition, the effects of acute CNO treatment on the expression of the neuronal activity marker c-Fos were examined in the mPFC as well as downstream target neuronal circuits using immunohistochemistry. Acute pharmacogenetic activation of mPFC excitatory neurons evoked a significant decrease in anxiety-like behaviour selectively on the elevated plus maze task, but not the open field test. Acute CNO treatment resulted in enhanced c-Fos-immunopositive cell number in the infralimbic, prelimbic and cingulate subdivisions of the mPFC. This was also accompanied by enhanced c-Fos-immunopositive cell number in multiple downstream circuits of the mPFC in CNO-treated hM3Dq animals. Acute pharmacogenetic activation of mPFC excitatory neurons reduces anxiety-like behaviour in a task-specific fashion accompanied by enhanced c-Fos expression in the mPFC and multiple target circuits implicated in the regulation of anxiety-like behaviour.

Original languageEnglish (US)
Pages (from-to)85-95
Number of pages11
JournalJournal of Biosciences
Volume43
Issue number1
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge Dr Shital Suryavanshi and Pankaj Dubey for their help and technical assistance. This work was supported by a TIFR intramural grant (VAV). The granting agency had no further role in the study design; in collection, analysis and interpretation of data; in writing the report; and in the decision to submit the paper for publication.

Publisher Copyright:
© 2018, Indian Academy of Sciences.

Keywords

  • Anxiety
  • chemogenetic
  • DREADDs
  • elevated plus maze
  • hM3Dq
  • mPFC
  • open field

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