RESUMO
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.
Assuntos
Sinalização do Cálcio/fisiologia , Proteínas de Ligação a DNA/fisiologia , Interneurônios/fisiologia , Neocórtex/fisiologia , Animais , Proteínas de Ligação a DNA/genética , Feminino , Masculino , Camundongos , Camundongos Knockout , Neocórtex/embriologia , Neocórtex/crescimento & desenvolvimento , Imagem Óptica , Proteínas com Domínio TRESUMO
We attempted to identify factors differentiating Agoraphobia with Panic Attacks (AG) from Panic Disorder (PD) patients. Twenty-three AG and 27 PD patients were compared. No significant difference in severity of illness was found. As predicted, the groups differed on a measure of anxiety-relevant cognitions developed for this study, the Anxious Thoughts and Tendencies scale (AT&T) (P less than 0.02). We suggest that differences in interpretation of panic attacks account for the development of of phobic avoidance behavior in some but not all PD patients. The intercorrelations among measures suggest that Panic Disorder may be conceptualized as having several independent although related components (panic attacks, general anxiety, phobic anxiety, and cognitive distortions).