Hypoxia-Induced Changes in Neuronal Network Properties

Abstract

Because of their high energetic demand, neurons within the mammalian central nervous system are extremely sensitive to changes in partial pressure of oxygen. Faced with acute hypoxic conditions, an organism must follow a complex and highly dynamic emergency plan to secure survival. Behavioral functions that are not immediately essential for survival are turned off, and critical behaviors (such as breathing) undergo a biphasic response. An augmentation of breathing is initially adaptive, whereas prolonged hypoxic conditions are better served by an energy-saving mode. However, the hypoxic response of an organism depends on many additional factors. Environmental conditions, the animal's age and health, and the pattern (continuous vs intermittent) and duration (chronic vs acute) of hypoxia greatly determine the specific course of a hypoxic response. Different forms of hypoxia can cause pathology or be used as therapy. Therefore, it is not surprising that the hypoxic response of an organism results from widespread and highly diverse reconfigurations of neuronal network functions in different brain areas that are accomplished by diverse hypoxic changes at all levels of the nervous system (i.e., molecular, cellular, synaptic, neuronal, network). Hypoxia-induced changes in synaptic transmission are generally depressive and result primarily from presynaptic mechanisms, whereas changes in intrinsic properties involve excitatory and inhibitory alterations involving the majority of K+, Na+, and Ca2+ channels. This article reviews the response of the nervous system to hypoxia, accounting for all levels of integration from the cellular to the network level, and postulates that a better understanding of the diversity of cellular events is only possible if cellular and network events are considered in a functional and organismal context.