2.1. Homeostasis levels

Living beings actively oppose their degradation in continuously changing environments by means of homeostasis [3] that supports the intrinsic bodily constants within acceptable limits. Maintenance of individual life requires evaluating and regulating its inner state. Homeostatic regularities can be traced to the level of particular cellular parameters, cells, in general, physiological systems of an organism, and an organism as a whole. In this study, we primarily focus on homeostasis of neurons and the nervous system. A cell, as a body, manifests complete homeostasis. This occurs not only to maintain biological constants but also to regulate physiological functions and motivational behavior. The behaving animal is sensitive to single neuronal spikes and even to their temporal patterning [4]. Moreover, a neuronal spike can serve as a tool of reaction for the whole animal [1]. Individual neurons act in concert to govern behavior [5].

At first glance, homeostatic mechanisms are not complicated. In theoretical research, the problem is often evaluated by the introduction of positive- and negative-feedback loops between the sensor and the metabolic flaw (e.g., [6, 7]). Attempts to model homeostatic regulation consider only simple homeostasis, with regulation of each variable described by the introduction of specific individual controllers. However, when homeostatic protection begins to work against a permanent environmental factor or severe injure, these mechanisms become ineffective and living systems utilize indirect paths to assign optimal parameters, depending on the situation.

Homeostatic function depends on sensors, which register deviations from the norm. Appearance of a metabolic flaw triggers the homeostatic device to compensate for the shortage. However, homeostatic resources may not be sufficient to restore disturbed functions. In these cases, living systems may try to change the environment, requiring the environment to be included in the interaction.<sup>1</sup>

The status of the internal environment is not sustainable for all life. Conditions remain stable only at intervals of time as compared to environmental variability. At these intervals, homeostasis counteracts weak disorders in the system and recovers initial conditions (direct regulation). Over time, adapting to strong external influences enables life to modify its parameters (indirect regulation). If the value of a deviated parameter is not restored, the organism may be able to maintain it by restructuring the optimum of other parameters. For example, stabilization of neuronal activity can be achieved by configuring both synapse efficiency and cell autonomous homeostasis [8]. Homeostasis readjusts to save some supreme quality criterion that distinguishes the living from the nonliving. The living entity keeps track of a special criterion the degree of remoteness from its destruction. This criterion determines the intensity of homeostatic protection. However, damage may reach such an extent that homeostasis is unable to overcome the irreversible destruction of the living system.

The nature of the general sensor for damage-recovery viability is unclear, though there are options that are significant to the survival of cells and the whole organism. These include energy (ATP level), excitability, intracellular pH levels, and concentration of certain proteins (caspases, cytokines, or antioxidants). These cannot be disregarded by the highest sensors, which could lead to death. For example, a supreme neuronal sensor might be excitability [1].
