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

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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.

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Acknowledgements

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.

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  1. Ankit Sood and Sourish Mukhopadhyay have contributed equally to the manuscript.

Authors and Affiliations

  1. Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India

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

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  1. Sthitapranjya Pati
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  2. Ankit Sood
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  3. Sourish Mukhopadhyay
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  4. Vidita A Vaidya
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Correspondence to Vidita A Vaidya.

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Corresponding editor: Aurnab Ghose

Corresponding editor: Aurnab Ghose

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Pati, S., Sood, A., Mukhopadhyay, S. et al. Acute pharmacogenetic activation of medial prefrontal cortex excitatory neurons regulates anxiety-like behaviour. J Biosci 43, 85–95 (2018). https://doi.org/10.1007/s12038-018-9732-y

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  • DOI: https://doi.org/10.1007/s12038-018-9732-y

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