Monoaminergic neurons innervate almost all brain areas. A. Noradrenaline. The noradrenergic neurons of the locus ceruleus project to the limbic and cortical regions, and to the thalamus, cerebellum, and spinal cord. They play an important role in the regulation of mood and attention. The noradrenergic neurons of cell groups A1 , A2, A5, and A7 project to more restricted regions.⁴ They are important for autonomic function. B. Dopamine. The dopaminergic neurons of the substantia nigra and the adjacent ventral tegmenta! area (VTA) project to the striatum and to regions in the neocortex. They are important in the initiation of movements and for emotional processes. Furthermore, there is a dopaminergic cell group in the hypothalamus that regulates neuroendocrine processes. C. Serotonin. The serotonergic neurons located in the raphe nuclei project to almost all parts of the brain and are involved in many functions including the regulation of emotional processes. D. Histamine. Histaminergic neurons are located in the tuberomammillary complex of the hypothalamus. They project to all parts of the brain and are important for arousal (the excited brain state). Modulation of neuronal activity by these monoamines is an important factor of well-balanced central nervous activity. Stress leads to hyperactivity of the monoamine neurons and thus to a dysregulation of neuronal activity. Currently available antidepressants are thought to adjust the balance between the different neurotransmitter systems.

Serotonergic nerve endings (schematic drawing, upper left) in the hippocampal formation release the neurotransmitter serotonin (gray balls), which binds to its receptors, the serotonin-1 A (5-HT_1A) receptors (orange). The three pseudo-color pictures demonstrate receptor binding in normal male tree shrews (left), in tree shrews that were submitted to chronic psychosocial stress (middle), and in stressed tree shrews that had received testosterone as a treatment (right). Colors indicate numbers of receptors in the different regions of the hippocampal formation: orange, high receptor numbers; yellow, moderate numbers; green, low numbers; purple, no receptors. Note that after chronic social stress receptor numbers are decreased, but that the normal receptor number is restored following testosterone treatment.

Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, β, and γ, serves as the machinery that transduces the extracellular signal to various effectors at the intracellular side of the plasma membrane, to the enzymes adenylyl cyclase or phospholipase. These enzymes catalyze the synthesis of second messengers, such as cyclic adenosine monophosphate (cAMP) and diacylglycerol, which regulate gene transcription in the nucleus. Transcripts (mRNA) are later translated into protein. Calcium ions released from intracellular stores and other second messengers activate protein kinases and phosphatases. This leads to phosphorylation and/or dephosphorylation of many intracellular proteins as well as ion channels that are located in the plasma membrane of the cell. Phosphorylation/dephosphorylation induces opening and closing of these channels and this modulates the electrical activity of the neuron. These dynamic cellular processes are accelerated during stress when neurotransmitter concentrations are elevated.

Schematic drawing of a CA3 pyramidal neuron plus its dendrites. Note the small soma in comparison to the highly arborized apical and basal dendrites. Inset; dendritic shafts can build up protrusions (spines) that form synapses with axons or dendrites from other neurons. Synapses are sites of signal transmission between neurons. Formation and disappearance of spines are regulated by many factors such as gonadal hormones. Chronic psychosocial stress reduces the arborization of the apical dendrites, thus reducing the surface area of the neuron with the consequence that the neuron receives less information from other neurons (see text for details).