Glycine receptor inhibition differentially affect selected neuronal populations of the developing Embryonic Cortex, as evidenced by the analysis of spontaneous calcium oscillations

Abstract

The embryonic developing cerebral cortex is characterized by the presence of distinctive cell types such as progenitor pools, immature projection neurons and interneurons. Each of these cell types is diverse on itself, but they all take part of the developmental process responding to intrinsic and extrinsic cues that can affect their calcium oscillations. Importantly, calcium activity is crucial for controlling cellular events linked to cell cycle progression, cell fate determination, specification, cell positioning, morphological development and maturation. Therefore, in this work we measured calcium activity in control conditions and in response to neurotransmitter inhibition. Different data analysis methods were applied over the experimental measurements including statistical methods entropy and fractal calculations, and spectral and principal component analyses. We found that developing projection neurons are differentially affected by classic inhibitory neurotransmission as a cell type and at different places compared to migrating interneurons, which are also heterogeneous in their response to neurotransmitter inhibition. This reveals important insights into the developmental role of neurotransmitters and calcium oscillations in the forming brain cortex. Moreover, we present an improved analysis proposing a Gini coefficient-based inequality distribution and principal component analysis as mathematical tools for understanding the earliest patterns of brain activity.