title: NPY+-, but not PV+- GABAergic neurons mediated long-range inhibition from infra- to prelimbic cortex.
abstract: Anxiety disorders are thought to reflect deficits in the regulation of fear memories. While the amygdala has long been considered a site of storage of fear memories, newer findings suggest that the prefrontal cortex (PFC) is essential in the regulation of amygdala-dependent memories and fear expression. Here, activation of the prelimbic cortex (PrL) enhances the expression of fear, while an elevated activity in the infralimbic cortex (IL) enhances fear extinction. Despite the presence of these facts, we still know very little about the synaptic interconnectivity within the PFC. The aim of the present study was to investigate the inhibitory circuits between prelimbic and IL using morphological and electrophysiological methods. Our immunohistochemical analysis revealed that the distribution of PV(+)- and NPY(+)-GABAergic neurons was strikingly different within the PFC. In addition, we provided the first experimental evidence that the pyramidal neurons in the PrL received a direct inhibitory input mediated by bipolar NPY(+)-GABAergic projection neurons in the IL. Deletion of the anxiety-related neuroligin 2 gene caused a decrease of this direct synaptic inhibition that originated from the IL. Thus, our data suggested that activation of the IL might not only directly activate the corresponding downstream anxiolytic pathway, but also suppress the PrL-related anxiogenic pathway and thus could differentially bias the regulation of fear expression and extinction.
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Saffari
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: Z
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kravchenko
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Hohoff
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: O
authors.initials: O
authors.lastname: Ambrée
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, University of Münster, Münster, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005108:Extinction, Psychological / Q000502:physiology*; D059330:GABAergic Neurons / Q000378:metabolism*; D008032:Limbic System / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000378:metabolism; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D010320:Parvalbumins