The raphe nuclei are the place of synthesis of the neurotransmitter serotonin, which plays an important role in mood regulation.

Traditionally the reticular nuclei are divided into three columns:[citation needed] The original functional differentiation was a division of caudal and rostral.

The medial RF is large and has long ascending and descending fibers, and is surrounded by the lateral reticular formation.

[citation needed] Existing on the sides of the medial reticular formation is its lateral cousin, which is particularly pronounced in the rostral medulla and caudal pons.

[clarification needed] The lateral RF is known for its ganglions and areas of interneurons around the cranial nerves, which serve to mediate their characteristic reflexes and functions.

[6][13][14][15] The ARAS is composed of several neural circuits connecting the dorsal part of the posterior midbrain and the ventral pons to the cerebral cortex via distinct pathways that project through the thalamus and hypothalamus.

[6][14][15] The ARAS is a collection of different nuclei – more than 20 on each side in the upper brainstem, the pons, medulla, and posterior hypothalamus.

[29] During sleep, neurons in the ARAS will have a much lower firing rate; conversely, they will have a higher activity level during the waking state.

[citation needed] Ascending reticular activation in cats can produce mydriasis,[34] which can result from prolonged pain.

[45] Physical or vascular damage to the brainstem disconnecting the red nucleus (midbrain) and the vestibular nuclei (pons) may cause decerebrate rigidity, which has the neurological sign of increased muscle tone and hyperactive stretch reflexes.

Because the rubrospinal tract only extends to the cervical spinal cord, it mostly acts on the arms by exciting the flexor muscles and inhibiting the extensors, rather than the legs.

[46] Damage to the medulla below the vestibular nuclei may cause flaccid paralysis, hypotonia, loss of respiratory drive, and quadriplegia.

[46] The term "reticular formation" was coined in the late 19th century by Otto Deiters, coinciding with Ramon y Cajal's neuron doctrine.

Allan Hobson states in his book The Reticular Formation Revisited that the name is an etymological vestige from the fallen era of the aggregate field theory in the neural sciences.

Eric Kandel describes the reticular formation as being organized in a similar manner to the intermediate gray matter of the spinal cord.

[citation needed] Moruzzi and Magoun first investigated the neural components regulating the brain's sleep-wake mechanisms in 1949.

[citation needed] As direct electrical stimulation of the brain could simulate electrocortical relays, Magoun used this principle to demonstrate, on two separate areas of the brainstem of a cat, how to produce wakefulness from sleep.

"[47] The latter was of particular interest, as this series of relays did not correspond to any known anatomical pathways for the wakefulness signal transduction and was coined the ascending reticular activating system (ARAS).

[citation needed] Next, the significance of this newly identified relay system was evaluated by placing lesions in the medial and lateral portions of the front of the midbrain.

In alternative fashion, cats with similarly placed interruptions to ascending auditory and somatic pathways exhibited normal sleeping and wakefulness, and could be awakened with physical stimuli.

Because these external stimuli would be blocked on their way to the cortex by the interruptions, this indicated that the ascending transmission must travel through the newly discovered ARAS.

The researchers proposed that a column of cells surrounding the midbrain reticular formation received input from all the ascending tracts of the brain stem and relayed these afferents to the cortex and therefore regulated wakefulness.