Early Actions of Neurotransmitters During Cortex Development and Maturation of Reprogrammed Neurons

Abstract

The development of the brain is shaped by a myriad of factors among which neurotransmitters play remarkable roles before and during the formation and maturation of synaptic circuits. Cellular processes such as neurogenesis, morphological development, synaptogenesis and maturation of synapses are temporary and spatially regulated by the local or distal influence of neurotransmitters in the developing cortex. Thus, research on this area has contributed to the understanding of fundamental mechanisms of brain development and to shed light on the etiology of various human neurodevelopmental disorders such as autism and Rett syndrome (RTT), among others. Recently, the field of neuroscience has been shaken by an explosive advance of experimental approaches linked to the use of induced pluripotent stem cells and reprogrammed neurons. This new technology has allowed researchers for the first time to model in the lab the unique events that take place during early human brain development and to explore the mechanisms that cause synaptopathies. In this context, the role of neurotransmitters during early stages of cortex development is beginning to be re-evaluated and a revision of the state of the art has become necessary in a time when new protocols are being worked out to differentiate stem cells into functional neurons. New perspectives on reconsidering the function of neurotransmitters include opportunities for methodological advances, a better understanding of the origin of mental disorders and the potential for development of new treatments.

Establishment of an a priori protocol for the implementation and interpretation of an in‐vitro testing battery for the assessment of developmental neurotoxicity

“…potassium channels, calcium channels or hyperpolarization-activated cyclic nucleotide-gated channel 1, the applicability domain of the DNT in vitro battery still needs to be established. (Cameron et al, 1998;Nguyen et al, 2001;Ojeda & Ávila, 2019;Xing & Huttner, 2020). Neurotransmitters mediate developmental processes such as cell proliferation (Haydar et al, 2000), neuronal differentiation (Salazar et al, 2008), neuronal migration (Komuro & Rakic, 1993;Murthy et al, 2014), synaptic maturation (Fu et al, 2012), neurite growth (Anelli et al, 2013) and cell death (Ikonomidou et al, 2001).…”

How Do Electric Fields Coordinate Neuronal Migration and Maturation in the Developing Cortex?

“…GABA influences radial and tangential migration through its various receptors depending on the migration step and exerts some of these actions through Ca 2+ influx signaling, due to the fact that that it functions as an excitatory neurotransmitter in early development and depolarizes immature neurons. GABA paracrine and chemoattractive actions have been documented by several authors (Horigane et al, 2019;Ojeda and Ávila, 2019).…”

“…Many studies on the role of NMDARs and AMPARs in migration are summarized in excellent reviews (Rakic and Komuro, 1995;Luhmann et al, 2015;Horigane et al, 2019;Ojeda and Ávila, 2019). In general, NMDAR and AMPAR blockade attenuates the migration of different types of immature neurons and NMDA physiological activation accelerates the movement.…”

“…Neurotransmitters are present throughout developing neural tissues, can be released by cells in close vicinity, i.e., neuroblasts or maturing neurons, and can act on migrating neurons in paracrine, non-synaptic, fashion (Spitzer, 2006;Luhmann et al, 2015;Ojeda and Ávila, 2019). Gap junctions, or electric synapses, undoubtedly also play roles during development, especially in electrically active zones, such as the subplate (SP) (Luhmann et al, 2018;Singh et al, 2019).…”

Children's Health in the Digital Age

“…Internet Addiction Disorder (IAD) is a disabling condition that calls for full consideration as it has a severe impact on young people's brain functioning. Internet addiction disorder (IAD), sometimes also called pathologic/problematic internet use (PIU), is widely defined in terms of an impulse control disorder characterized by uncontrolled Internet use [58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]. The disorder is associated with significant functional impairment and/or clinically measurable distress, anxiety, depression and other psychopathological symptoms .…”