Fear/anxiety and sleep/wakefulness seem to be universal behavioural phenomena, since they are present in all mammalian and a number of non-mammalian species that have been carefully studied so far. Alterations of the generation or control of these behaviours may lead to sleep disorders, to states of dramatically reduced consciousness (absence de l´esprit) or of hyperexcitability (epilepsy), or to anxiety disorders (such as panic disorders, phobias or posttraumatic stress disorders). These disorders affect millions of people: for example, up to 20% of the German population develop an anxiety disorder during life, and of those affected less than 25% consider treatment effective! Scientists currently think that these disorders are complex and result from a combination of genetic, environmental, psychological, and developmental factors, which, in turn, affect proper function of the relevant circuitries in the brain. Identification of the underlying mechanisms is thus central to the development of therapeutic targets for these diseases.
Several parts of the brain contribute to the regulation of the sleep/wake cycle. One key structure is the thalamus, situated in the diencephalon (further information). During wakefulness and arousal, the thalamus transfers the bulk of signals from the external world to the cortex for final information processing and selection by memory systems. During sleep, neurons in the thalamus produce slow-rhythmic patterns of electrical activity. This impairs the faithful signal transfer from the external world (explaining the common experience that responsiveness of the brain to external stimuli is reduced during sleep!), but also seems to allow the “replay” of internal brain signals for memory consolidation (memory is stabilized after sleep!). An impaired control of these functions can lead to stages of dramatically reduced consciousness, characterizing, for instance, absence seizures during one form of epilepsies that is particularly frequent in children. Research in the Institute of Physiology I has helped to characterize the factors controlling the dual mode of function of the thalamus, and, in particular, has identified molecular factors relating to absence epilepsy (Pflügers Arch. 2015a; 2015b; e-Neuroforum 2015).
Key areas of the brain involved in fear and anxiety, are the amygdala, the hippocampus and the prefrontal cortex. The amygdala is an almond-shaped structure deep in the brain that is believed to be a communications hub between the parts of the brain that process incoming sensory signals (such as the thalamus, see above) and the parts that interpret these signals (such as the prefrontal cortex, see below; further information). It can alert the rest of the brain that a threat is present and trigger a fear or anxiety response. It appears that the amygdala plays a critical role in anxiety disorders involving very distinct fears, such as fears of dogs, spiders, flying, or disorders following experience of a traumatic event. The hippocampus is the part of the brain that encodes threatening events into memories. The prefrontal cortex, in turn, is a structure of high hierarchical rank in the brain, which exerts an executive control function over the fear circuits in the amygdala. This allows re-interpretation and re-appraisal of signals, for instance one that had been initially encountered in a fearful situation and now turns out to be harmless, and therefore leads to extinction of fear memories. The functional balance between these areas governs fear and anxiety behaviour, and distortion of this balance is a key factor for anxiety disorders. Research in the Institute of Physiology I has helped to characterize the brain circuitries underlying this balance and has identified novel brain messenger molecules supporting their control (Bild der Wiss 08/2007; Neuroforum Artikel des Quartals; NeuronNPS; PhysRev; FAZ 28.01.15).