title: Distinct calcium signals in developing cortical interneurons persist despite disorganization of cortex by Tbr1 KO.
abstract: Cortical development involves the structuring of network features by genetically programmed molecular signaling pathways. Additionally, spontaneous ion channel activity refines neuronal connections. We examine Ca(2+) fluctuations in the first postnatal week of normal mouse neocortex and that expressing knockout of the transcription factor T-brain-1 (Tbr1): a signaling molecule in cortical patterning and differentiation of excitatory neurons. In cortex, glutamatergic neurons express Tbr1 just before the onset of population electrical activity that is accompanied by intracellular Ca(2+) increases. It is known that glutamatergic cells are disordered with Tbr1 KO such that normal laying of the cortex, with newer born cells residing in superficial layers, does not occur. However, the fate of cortical interneurons is not well studied, nor is the ability of Tbr1 deficient cortex to express normal physiological activity. Using fluorescent proteins targeted to interneurons, we find that cortical interneurons are also disordered in the Tbr1 knockout. Using Ca(2+) imaging we find that population activity in mutant cortex occurs at normal frequencies with similar sensitivity to GABAA receptor blockade as in nonmutant cortex. Finally, using multichannel fluorescence imaging of Ca(2+) indicator dye and interneurons labeled with red fluorescent protein, we identify an additional Ca(2+) signal in interneurons distinct from population activity and with different pharmacological sensitivities. Our results show the population activity described here is a robust property of the developing network that continues in the absence of an important signaling molecule, Tbr1, and that cortical interneurons generate distinct forms of activity that may serve different developmental functions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 705-720, 2016.
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.|Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, 98101.
authors.forename: C R
authors.initials: CR
authors.lastname: Easton
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: C W
authors.initials: CW
authors.lastname: Dickey
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: S P
authors.initials: SP
authors.lastname: Moen
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: K E
authors.initials: KE
authors.lastname: Neuzil
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: Z
authors.initials: Z
authors.lastname: Barger
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: T M
authors.initials: TM
authors.lastname: Anderson
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.
authors.forename: W J
authors.initials: WJ
authors.lastname: Moody
authors.affiliation: Department of Biology, University of Washington, Seattle, Washington, 98195.|Department of Neurological Surgery, University of Washington, Seattle, Washington, 98195.|Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, 98101.
authors.forename: R F
authors.initials: RF
authors.lastname: Hevner
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D061848:Optical Imaging; D020825:T-Box Domain Proteins
chemical_list: D004268:DNA-Binding Proteins; D020825:T-Box Domain Proteins; C492271:Tbr1 protein, mouse
keywords: Tbr1; cortex; development; interneurons; spontaneous activity