Cell injury/death leads to Neuronal network function, Decreased

Under physiological conditions, in the developing nervous system, apoptosis occurs during the process of synaptogenesis, where competition leads to the loss of excess neurons and to the connection of the appropriate neurons (Buss et al., 2006; Mennerick and Zorumski, 2000; Oppenheim, 1991). When a stressor increases the number of apoptotic cells this KE has a negative effect on synaptogenesis as the reduced number of neurons (besides the ones that have been already eliminated through the physiological process of apoptosis) provides limited dendritic fields for receiving synaptic inputs from incoming axons. At the same time the loss of neurons also means that there are less axons to establish synaptic contacts (Olney, 2014), leading to reduced synaptogenesis. The ability of a neuron to communicate is based on neural network formation that relies on functional synapse establishment (Colón-Ramos, 2009). The main roles of synapses are the regulation of intercellular communication in the nervous system, and the information flow within neural networks. The connectivity and functionality of neural networks depends on where and when synapses are formed. Therefore, the decreased synapse formation due to cell death during the process of synaptogenesis is critical and leads to decrease of neural network formation and function in the adult brain.

Synaptic transmission and plasticity require the integrity of the anatomical substrate. The connectivity of axons emanating from one set of cells to post-synaptic side of synapse on the dendrites of the receiving cells must be intact for effective communication between neurons. Changes in the placement of cells within the network due to delays in neuronal migration, the absence of a full formation of dendritic arbors and spine upon which synaptic contacts are made, and the lagging of transmission of electrical impulses due to insufficient myelination will individually and cumulatively impair synaptic function.

Therefore, chemicals inducing neuronal cell death by apoptosis or necrosis, or interfering with a particular system of neurotransmitters, will alter network structure and function.

Whereas the quantification of cell injury and death is straightforward, the quantification of the decreased network function is much more qualitative than quantitative, precluding a quantitative understanding of the linkage for this KER.

Support for the link between cell injury/death and decreased neuronal network formation and function can be found in rat, mouse and minnow. (for references, see empirical evidences)