Long-range inhibition from prelimbic to cingulate areas of the medial prefrontal cortex enhances network activity and response execution

Nao Utashiro, Duncan Archibald Allan MacLaren, Yu-Chao Liu, Kaneschka Yaqubi, Birgit Wojak and Hannah Monyer ()
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Nao Utashiro: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)
Duncan Archibald Allan MacLaren: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)
Yu-Chao Liu: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)
Kaneschka Yaqubi: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)
Birgit Wojak: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)
Hannah Monyer: Department of Clinical Neurobiology at the Medical Faculty of the Heidelberg University and of the German Cancer Research Center (DKFZ)

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract It is well established that the medial prefrontal cortex (mPFC) exerts top-down control of many behaviors, but little is known regarding how cross-talk between distinct areas of the mPFC influences top-down signaling. We performed virus-mediated tracing and functional studies in male mice, homing in on GABAergic projections whose axons are located mainly in layer 1 and that connect two areas of the mPFC, namely the prelimbic area (PrL) with the cingulate area 1 and 2 (Cg1/2). We revealed the identity of the targeted neurons that comprise two distinct types of layer 1 GABAergic interneurons, namely single-bouquet cells (SBCs) and neurogliaform cells (NGFs), and propose that this connectivity links GABAergic projection neurons with cortical canonical circuits. In vitro electrophysiological and in vivo calcium imaging studies support the notion that the GABAergic projection neurons from the PrL to the Cg1/2 exert a crucial role in regulating the activity in the target area by disinhibiting layer 5 output neurons. Finally, we demonstrated that recruitment of these projections affects impulsivity and mechanical responsiveness, behaviors which are known to be modulated by Cg1/2 activity.

Date: 2024
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DOI: 10.1038/s41467-024-50055-z

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