Chapter 7 - Network Control Mechanisms: Cellular Inputs, Neuroactive Substances, and Synaptic Changes

Abstract

Cellular inputs, neuroactive substances, and synaptic changes are critical elements in neuronal network control and function. Cellular inputs to principal cells in a network nucleus include projection neurons from other nuclei in the network, inputs from neurons from other networks, and interneurons, as well as glia within the network nucleus. Each of these inputs has the potential to exert a major influence on the ongoing activity of a neuronal network. The pattern of firing of these inputs and the nature of the neuroactive substance released onto the principal neurons of each network nucleus plus the intrinsic activity of the principal cells govern the role of that nucleus in network function. In addition to the synaptic effects of the released neuroactive substances, these agents can also exert network-wide effects through volume transmission via the extracellular and cerebrospinal fluids. Neuroactive agents that induce network-wide effects include gamma-aminobutyric acid, glutamate, serotonin, and adenosine, as well as cytokines, among others. These network-wide effects can exert major influences on network function in sleep states, learning disorders, and central nervous system (CNS) disorders. With repetitive activation, these influences can lead to long-term changes in network function that involve changes in synaptic strength, which are associated with events, such as long-term potentiation, that potentially lead to molecular and structural changes. These changes are mediated, in part, by protein synthesis, including the synthesis of immediate early genes, such as c-fos, and this can lead to activation of molecular cascades, leading to trophic factor release. These events can lead to changes in the formation of dendritic spines, synaptogenesis, axonal sprouting, and neurogenesis. Knowledge about the roles of these elements and other influences can lead to a better understanding of how neuronal networks of the brain exert their function as well as shed light on network dysfunctions that occur in CNS disorders and ultimately lead to improved therapy of these disorders.