title: GABAB receptors in maintenance of neocortical circuit function.
abstract: Activation of metabotropic GABAB receptors (GABABRs) enhances tonic GABA current and substantially increases the frequency of spontaneous seizures. Despite the and pro-epileptic consequences of GABABR activation, mice lacking functional GABAB receptors (GABAB1R KO mice) exhibit clonic and rare absence seizures. To examine these mutant mice further, we recorded excitatory and inhibitory synaptic inputs and tonic mutant GABA currents from Layer 2 neocortical pyramidal neurons of GABAB1R WT and KO mice (P30-40). Tonic current was increased while the frequency of synaptic inputs was unchanged in KO mice relative to WT littermates. The neocortical laminar distribution of interneuron subtypes derived from the medial ganglionic eminence (MGE) was also not statistically different in KO mice relative to WT while the number of calretinin-positive, caudal GE-derived cells in Layer 1 was reduced. Transplantation of MGE progenitors obtained from KO mice lacking functional GABAB1R did not increase tonic inhibition in the host brain above that of media-injected controls. Taken together, these results suggest a complex role for GABAB receptors in mediating neocortical circuit function.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Sebe
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Looke-Stewart
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 941432, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: scott.baraban@ucsf.edu.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D064032:Calbindin 2 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology* / Q000601:surgery; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D064032:Calbindin 2; D004268:DNA-Binding Proteins; C499942:Grhl3 protein, mouse; D009478:Neuropeptide Y; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D010091:Oximes; D010880:Piperidines; D011743:Pyrimidines; D018080:Receptors, GABA-B; C464854:SNAP7941; D014157:Transcription Factors; C078793:NNC 711; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid
keywords: GABAB; MGE; Neocortex; Tonic inhibition