Glycine Receptor Inhibition Differentially Affect Selected Neuronal Populations of the Developing Embryonic Cortex, as Evidenced by the Analysis of Spontaneous Calcium Oscillations.

Denisse Ávila,Ariel Ávila,Eduardo Aedo,Miguel Sánchez-Hechavarria,Claudio Ávila

doi:10.3390/ijms21218013

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.

Highlights

The cerebral cortex is where the higher order functions of the brain reside and understanding its developmental process can help us to understand the etiology of important cognitive dysfunctions and mental disorders [1]
Calcium signal was measured at the ventricular zone (VZ), intermediate zone (IZ) and cortical plate (CP) regions, tracking Fluo4 fluorescent intensity on time and on individual developing projection neurons (Figure 1A,B)
We performed a power spectrum analysis of the acquired signals and, grouped power spectra seemed to differ at the ventricular zone (Figure 2C), average peak power, peak frequency and power spectral density (PSD) did not vary across regions and conditions (Figure 2D–F)

Summary

Introduction

The cerebral cortex is where the higher order functions of the brain reside and understanding its developmental process can help us to understand the etiology of important cognitive dysfunctions and mental disorders [1]. Projection neurons are born in the dorsal telencephalon, at the ventricular zone, and account for the majority of cortical neurons After development, they will release glutamate and provide excitation to cortical circuits. They will release glutamate and provide excitation to cortical circuits Dysfunction on their development can cause serious brain abnormalities ranging from minor anatomical changes to marked micro or macrocephaly. These abnormalities can be linked to numerous mental disorders including epilepsy, learning disabilities and mental retardation [2]. They characteristically migrate to the cortex adopting their final position integrating into cortical circuits alongside projection neurons [5]

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Results

Conclusion