Serotonin (5-hydroxytryptamine, 5HT) , a monoamine neurotransmitter, plays an important role in many behaviors including sleep, appetite, memory, sexual behavior, neuroendocrine function, and mood. In the brain, the highest level of serotonin is found in the dorsal and median raphe nuclear complex. Neurons in the raphe system project beyond the raphe nucleus, most often in the lateral direction. There are also many serotonergic neurons found in the reticular region of the lower brain stem. For convenience, neurons in the brain stem are often divided into a caudal system and a rostral system. Those in the caudal system descend to the spinal chord along many pathways and are largely involved in sensory, motor, and autonomic functioning. Serotonergic cells in the rostral system of the brainstem largely terminate in the dorsal and median raphe nuclei.
Another major serotonergic pathway in the brain is one going from the cerebellum that terminates in the cerebellar cortex and the cerebellar nuclei. Many serotonergic neurons contribute to this pathway. The presence of serotonin has also been observed in the pons, medulla, thalamus, hypothalamus, substantia nigra, and locus coeruleus.
Serotonin is synthesized from the amino acid precursor tryptophan, packaged into vesicles, and released into the synapse following an action potential. Once in the synapse, serotonin can interact with both the pre- and postsynaptic receptors. However, immediately after reacting with the pre- and postsynaptic receptors, it is critically important that serotonin be removed from the synapse.
Re-uptake, the process of removing transmitters after release, determines the extent, duration, and spatial domain of receptor activation. Any transmitter not removed from the cleft prevents further signals from getting through. Active removal reduces the level of transmitter in the cleft faster than diffusion, constrains the effects of released transmitter to smaller areas, and allows at least part of the released chemical to be recycled for further use. Re-uptake is carried out by transporter proteins which bind to the released transmitter and carry it across the plasma membrane into the pre-synaptic neuron.