Early postnatal development of neocortex-wide activity patterns in GABAergic and pyramidal neurons

Abstract

Before the onset of sensory experience, developing circuits generate synchronised activity that will not only influence its wiring, but ultimately contribute to behaviour. These complex functions rely on widely distributed cortical that simultaneously operate at multiple spatiotemporal scales. The timing of GABAergic maturation appears to align with the developmental trajectories of cortical regions, playing a crucial role in the functional development of individual brain areas. While local connectivity in cortical microcircuits has been extensively studied, the dynamics of brain-wide functional maturation, especially for GABAergic populations, remain underexplored. In this project, a dual-colour widefield calcium imaging approach was developed to examine the neocortex-wide dynamics of cortical GABAergic and excitatory neurons simultaneously across early postnatal development. This study provides the first broad description of neocortex-wide GABAergic developmental trajectories and their cross-talk with excitatory dynamics during the second and third postnatal weeks. The observed spontaneous activity revealed discrete activity domains, reflecting the modular organisation of the cortex. Both excitatory and GABAergic population exhibited an increase in the size and frequency of activity motifs, as well as changes in motif variability. However, as they matured, the distribution of these spatiotemporal properties displayed divergent trajectories across populations and regions. These findings suggest fundamental differences in the spatial organisation of both populations, indicating potential distinct roles in cortical network function development. Moreover, while excitatory and GABAergic dynamics exhibited high correlations, brief deviations from perfect timing were observed. This correlation patterns changed significantly during development and across regions, with the two populations gradually becoming more correlated as they matured. Manipulating inhibition in vivo disrupted these fluctuations, impacting both local activity and the wider functional network.These findings provide valuable insights into the developmental trajectories of spontaneous activity patterns in excitatory and GABAergic cell populations during early postnatal development. The interplay between both neuronal populations plays a critical role in shaping activity patterns, and understanding the underlying mechanisms of their development can provide valuable insights into neurodevelopmental disorders

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