Articles written in Journal of Biosciences

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


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

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