Abstract
During development, cortical circuits are remodeled by spontaneous and sensory-evoked activity via alteration of the expression of wiring molecules. An intriguing question is how physiological neuronal activity modifies the expression of these molecules in developing cortical networks. Here, we addressed this issue, focusing on brain-derived neurotrophic factor (BDNF), one of the factors underlying cortical wiring. Real-time imaging of BDNF promoter activity in organotypic slice cultures revealed that patterned stimuli differentially regulated the increase and the time course of the promoter activity in upper layer neurons. Calcium imaging further demonstrated that stimulus-dependent increases in the promoter activity were roughly proportional to the increase in intracellular Ca2+ concentration per unit time. Finally, optogenetic stimulation showed that the promoter activity was increased efficiently by patterned stimulation in defined cortical circuits. These results suggest that physiological stimulation patterns differentially tune activity-dependent gene expression in developing cortical neurons via cortical circuits, synaptic responses, and alteration of intracellular calcium signaling.
Highlights
Neuronal activity plays a crucial role in the formation of functional connections during development
To study neuronal activity-dependent Bdnf promoter activity in individual cortical neurons, we performed live imaging with a luciferase assay in organotypic rat cortical cultures (Yamamoto et al, 1992)
We demonstrated spatiotemporal regulation of Bdnf promoter activity in the cortex by pharmacological and physiological stimulation
Summary
Neuronal activity plays a crucial role in the formation of functional connections during development This activity-dependent circuit formation has been well characterized in the sensory cortex: Spontaneous and sensory-evoked neuronal activity remodels neuronal connections in the visual and somatosensory cortex (Katz and Shatz, 1996; Feldman and Brecht, 2005; Hensch, 2005; Ackman and Crair, 2014). Such remodeling is regulated by activity-dependent expression of molecules that affect axon and dendrite behavior, indicating that neuronal activity is adequately converted into molecular signals (Iwasato et al, 2000; Uesaka et al, 2005, 2007; Mizuno et al, 2007; Yamada et al, 2010; Mire et al, 2012; Hayano et al, 2014; Munz et al, 2014; Suárez et al, 2014; Nakashima et al, 2019). Theses characteristic neural activities are thought to contribute to circuit remodeling, but few studies have investigated how patterned activity influences gene expression (Lee et al, 2017; Tyssowski et al, 2018)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
