title: Sex differences in GABA(B)R-GIRK signaling in layer 5/6 pyramidal neurons of the mouse prelimbic cortex.
abstract: The medial prefrontal cortex (mPFC) has been implicated in multiple disorders characterized by clear sex differences, including schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, depression, and drug addiction. These sex differences likely represent underlying differences in connectivity and/or the balance of neuronal excitability within the mPFC. Recently, we demonstrated that signaling via the metabotropic γ-aminobutyric acid receptor (GABABR) and G protein-gated inwardly-rectifying K(+) (GIRK/Kir3) channels modulates the excitability of the key output neurons of the mPFC, the layer 5/6 pyramidal neurons. Here, we report a sex difference in the GABABR-GIRK signaling pathway in these neurons. Specifically, GABABR-dependent GIRK currents recorded in the prelimbic region of the mPFC were larger in adolescent male mice than in female counterparts. Interestingly, this sex difference was not observed in layer 5/6 pyramidal neurons of the adjacent infralimbic cortex, nor was it seen in young adult mice. The sex difference in GABABR-GIRK signaling is not attributable to different expression levels of signaling pathway components, but rather to a phosphorylation-dependent trafficking mechanism. Thus, sex differences related to some diseases associated with altered mPFC function may be explained in part by sex differences in GIRK-dependent signaling in mPFC pyramidal neurons.
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Marron Fernandez de Velasco
authors.affiliation: Department of Neuroscience, University of Minnesota, 6-145 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hearing
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.
authors.forename: Zhilian
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Victoria
authors.affiliation: IDINE, Departmento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla La Mancha, C/Almansa 14, 02006, Albacete, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Luján
authors.affiliation: Department of Pharmacology, University of Minnesota, 6-120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA. Electronic address: wickm002@umn.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wickman
mesh_terms: D000818:Animals; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000502:physiology; D017397:Prefrontal Cortex / Q000254:growth & development / Q000502:physiology* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D018080:Receptors, GABA-B / Q000378:metabolism*; D012727:Sex Characteristics; D015398:Signal Transduction / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018080:Receptors, GABA-B
keywords: GABA; GIRK; Kir3; Medial prefrontal cortex; Sex differences; Slice electrophysiology
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