Features of Neural Network Formation and Their Functions in Primary Hippocampal Cultures in the Context of Chronic TrkB Receptor System Influence

Abstract

Discovering the mechanisms underlying homeostatic regulation in brain neural network formation and stability processes is one of the most urgent tasks in modern neuroscience. Brain-derived neurotrophic factor (BDNF) and the tropomyosin-related kinase B (TrkB) receptor system have long been considered the main regulators of neuronal survival and differentiation. The elucidation of methods for studying neural network activity makes investigating the complex mechanisms underlying neural network structure reorganization during development and detecting new mechanisms for neuronal activity remodeling possible. In this in vitro study, we investigated the effects of chronic BDNF (the main TrkB stimulator) and ANA-12 (a TrkB receptor system blocker) administration on the formation of neural-glial networks. The formation of spontaneous bioelectrical activity and functional neural structure depend on TrkB receptors, and blocking TrkB receptors inhibits full bioelectrical activity development. Cross-correlation analysis demonstrated the decisive role of TrkB in the formation and “strengths” of activity centers. Even though an appropriate ANA-12 concentration is non-toxic to nerve cells, numerous cells in culture medium containing this reagent do not exhibit metabolic activity and are not functionally involved in signal transmission processes. Electron microscopy studies revealed that chronically influencing the TrkB receptor system significantly alters synaptic and mitochondrial apparatus capture in cells, and functional analysis of mitochondrial activity confirmed these findings. Because knowledge of interactions between TrkB-mediated regulation and the mitochondrial state under normal conditions is rather limited, data on these relationships are particularly interesting and require further investigation. Thus, we assume that the molecular cascades mediated by TrkB actively participate in the formation of functionally complete brain neural networks.

Brain-Derived Neurotrophic Factor (BDNF) Preserves the Functional Integrity of Neural Networks in the β-Amyloidopathy Model in vitro

“…Investigation of neural networks as the minimal functional unit of the nervous system responsible for the processes of reconsolidation and storage of information is considered one of the principal aspects of studies on the neurodegeneration processes. A neural network is not only a functionally connected complex of neurons but also a single functional ensemble capable of responding in a consolidated manner to changes caused by both external and internal stimuli ( Yuste, 2015 ; Mishchenko et al, 2019 ). A single neural network in the native brain is extremely difficult to study and cannot be examined in a comprehensive manner at this time.…”

Neuroprotective Effect of HIF Prolyl Hydroxylase Inhibition in an In Vitro Hypoxia Model

“…A single application of the inhibitor was performed on day 14 in vitro grown cultures (DIV14). The formation of mature chemical synapses and stable neuronal network activity by DIV14 has been shown previously [41][42][43].…”

“…A single application of the inhibitor was performed on day 14 in vitro grown cultures (DIV14). The formation of mature chemical synapses and stable neuronal network activity by DIV14 has been shown previously [41][42][43]. Hippocampus has a relatively simple cellular composition and is genetically predisposed to form local neural networks; therefore, the use of primary cultures obtained from this brain region is preferred for in vitro studies on neuron-glial networks.…”

BDNF Overexpression Enhances the Preconditioning Effect of Brief Episodes of Hypoxia, Promoting Survival of GABAergic Neurons

“…So, these negative effects can be explained by the suppression of BDNF synthesis in control cultures after hypoxia. It has been shown that BDNF is necessary for the consolidation of long-term synaptic plasticity [35,36]. The expression of BDNF during chronic intermittent hypoxia decreases along with the expression of plasmin, which transforms pro-BDNF to BDNF; that is, BDNF synthesis is also attenuated.…”