The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formation make up a complex set of networks in the core of the brainstem that extend from the upper part of the midbrain to the lower part of the medulla oblongata. The reticular formation includes ascending pathways to the cortex in the ascending reticular activating system (ARAS) and descending pathways to the spinal cord via the reticulospinal tracts. Neurons of the reticular formation, particularly those of the ascending reticular activating system, play a crucial role in maintaining behavioral arousal and consciousness. The overall functions of the reticular formation are modulatory and premotor, involving somatic motor control, cardiovascular control, pain modulation, sleep and consciousness, and habituation. The modulatory functions are primarily found in the rostral sector of the reticular formation and the premotor functions are localized in the neurons in more caudal regions. The reticular formation is divided into three columns: raphe nuclei (median), gigantocellular reticular nuclei (medial zone), and parvocellular reticular nuclei (lateral zone). The raphe nuclei are the place of synthesis of the neurotransmitter serotonin, which plays an important role in mood regulation. The gigantocellular nuclei are involved in motor coordination. The parvocellular nuclei regulate exhalation. The reticular formation is essential for governing some of the basic functions of higher organisms and is one of the phylogenetically oldest portions of the brain. Structure The human reticular formation is composed of almost 100 brain nuclei and contains many projections into the forebrain, brainstem, and cerebellum, among other regions. It includes the reticular nuclei, reticulothalamic projection fibers, diffuse thalamocortical projections, ascending cholinergic projections, descending non-cholinergic projections, and descending reticulospinal projections. The reticular formation also contains two major neural subsystems, the ascending reticular activating system and descending reticulospinal tracts, which mediate distinct cognitive and physiological processes. It has been functionally cleaved both sagittally and coronally. Traditionally the reticular nuclei are divided into three columns: In the median column – the raphe nuclei In the medial column – gigantocellular nuclei (because of larger size of the cells) In the lateral column – parvocellular nuclei (because of smaller size of the cells) The original functional differentiation was a division of caudal and rostral. This was based upon the observation that the lesioning of the rostral reticular formation