TY - JOUR
T1 - Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum
AU - de Kloet, Sybren F.
AU - Bruinsma, Bastiaan
AU - Terra, Huub
AU - Heistek, Tim S.
AU - Passchier, Emma M.J.
AU - van den Berg, Alexandra R.
AU - Luchicchi, Antonio
AU - Min, Rogier
AU - Pattij, Tommy
AU - Mansvelder, Huibert D.
N1 - Funding Information: HDM received funding for this work from the Netherlands Organization for Scientific Research (NWO; VICI grant 865.13.002), European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2), and NWO Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.
AB - The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.
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U2 - https://doi.org/10.1038/s41467-021-22260-7
DO - https://doi.org/10.1038/s41467-021-22260-7
M3 - Article
C2 - 33790281
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1994
ER -