title: Function and developmental origin of a mesocortical inhibitory circuit.
abstract: Midbrain ventral tegmental neurons project to the prefrontal cortex and modulate cognitive functions. Using viral tracing, optogenetics and electrophysiology, we found that mesocortical neurons in the mouse ventrotegmental area provide fast glutamatergic excitation of GABAergic interneurons in the prefrontal cortex and inhibit prefrontal cortical pyramidal neurons in a robust and reliable manner. These mesocortical neurons were derived from a subset of dopaminergic progenitors, which were dependent on prolonged Sonic Hedgehog signaling for their induction. Loss of these progenitors resulted in the loss of the mesocortical inhibitory circuit and an increase in perseverative behavior, whereas mesolimbic and mesostriatal dopaminergic projections, as well as impulsivity and attentional function, were largely spared. Thus, we identified a previously uncharacterized mesocortical circuit contributing to perseverative behaviors and found that the diversity of dopaminergic neurons begins to be established during their progenitor phase.
authors.affiliation: Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kabanova
authors.affiliation: Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Milan
authors.initials: M
authors.lastname: Pabst
authors.affiliation: Functional Architecture of Memory Unit, Mercator Research Group, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Lorkowski
authors.affiliation: Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Braganza
authors.affiliation: Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Boehlen
authors.affiliation: Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Negar
authors.initials: N
authors.lastname: Nikbakht
authors.affiliation: Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany.
authors.forename: Leonie
authors.initials: L
authors.lastname: Pothmann
authors.affiliation: Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Ankita R
authors.initials: AR
authors.lastname: Vaswani
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Musgrove
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Donato A
authors.initials: DA
authors.lastname: Di Monte
authors.affiliation: Functional Architecture of Memory Unit, Mercator Research Group, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Sauvage
authors.affiliation: 1] Laboratory of Experimental Epileptology and Cognition Research, Department of Epileptology, University of Bonn, Bonn, Germany. [2] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.affiliation: Neurodevelopmental Genetics, Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn, Bonn, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blaess
mesh_terms: D000818:Animals; D001288:Attention / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology; D005971:Glutamates / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D051379:Mice; D009415:Nerve Net / Q000254:growth & development* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D012201:Reward; D017557:Ventral Tegmental Area / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D005971:Glutamates; D005680:gamma-Aminobutyric Acid