Reticular formation

showing the pontine reticular formation labeled as #9 The human reticular formation is composed of almost 100 nuclei and contains many projections into the forebrain, brainstem, and cerebellum, among other regions. • 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 induces a hypersomnia in the cat brain, while lesioning the caudal portion causes insomnia. This study has led to the idea that the caudal portion inhibits the rostral portion of the reticular formation. Sagittal division reveals more morphological distinctions. The raphe nuclei form a ridge in the middle of the reticular formation, and, directly to its periphery, there is a division called the medial reticular formation. The medial RF is large and has long ascending and descending fibers, and is surrounded by the lateral reticular formation. The lateral RF is close to the motor nuclei of the cranial nerves, and mostly mediates their function. Medial and lateral reticular formation The medial reticular formation and lateral reticular formation are two columns of nuclei with ill-defined boundaries that send projections through the medulla and into the midbrain. The nuclei can be differentiated by function, cell type, and projections of efferent or afferent nerves. Moving caudally from the rostral midbrain, at the site of the rostral pons and the midbrain, the medial RF becomes less prominent, and the lateral RF becomes more prominent. Existing on the sides of the medial reticular formation is its lateral cousin, which is particularly pronounced in the rostral medulla and caudal pons. Out from this area spring the cranial nerves, including the very important vagus nerve. 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. ==Major subsystems==

The subsystems of the reticular formation are the ascending reticular activating system, and the descending reticular system. Structure 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. The thalamic pathway consists primarily of cholinergic neurons in the pontine tegmentum, whereas the hypothalamic pathway is composed primarily of neurons that release monoamine neurotransmitters, namely dopamine, norepinephrine, serotonin, and histamine. The ARAS consists of evolutionarily ancient areas of the brain, which are crucial to the animal's survival and protected during adverse periods, such as during inhibitory periods of animal hypnosis also known as Totstellreflex. The ascending reticular activating system which sends neuromodulatory projections to the cortex - mainly connects to the prefrontal cortex. There seems to be low connectivity to the motor areas of the cortex. composed of two ascending mesopontine tegmental pathways rostrally situated between the mesencephalon and the centrum semiovale. Cholinergic activity is highest when in an awake state and during REM sleep, and is minimal in non-REM sleep Cholinergic activation in the RAS results in increased acetylcholine release in these areas. Glutamate has also been suggested to play an important role in determining the firing patterns of the tegmental cholinergic neurons. It has been recently reported that significant portions of posterior PPN cells are electrically coupled. It appears that this process may help coordinate and enhance rhythmic firing across large populations of cells. This unifying activity may help facilitate signal propagation throughout the RAS and promote sleep-wake transitions. It is estimated that 10 to 15% of RAS cells may be electrically coupled. More recent work has indicated that the neuronal messenger nitric oxide (NO) may also play an important role in modulating the activity of the noradrenergic neurons in the RAS. NO diffusion from dendrites regulates regional blood flow in the thalamus, where NO concentrations are high during waking and REM sleep and significantly lower during slow-wave sleep. Furthermore, injections of NO inhibitors have been found to affect the sleep-wake cycle and arousal. There are distinct differences in the brain's electrical activity during periods of wakefulness and sleep: Low voltage fast burst brain waves (EEG desynchronization) are associated with wakefulness and REM sleep (which are electrophysiologically similar); high voltage slow waves are found during non-REM sleep. Generally speaking, when thalamic relay neurons are in burst mode the EEG is synchronized and when they are in tonic mode it is desynchronized. 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. In order that the brain may sleep, there must be a reduction in ascending afferent activity reaching the cortex by suppression of the ARAS. Attention The ARAS also helps mediate transitions from relaxed wakefulness to periods of high attention. Bilateral damage to the ARAS nuclei may lead to coma or death. Direct electrical stimulation of the ARAS produces pain responses in cats and elicits verbal reports of pain in humans. Ascending reticular activation in cats can produce mydriasis, Some pathologies of the ARAS may be attributed to ageing, as there appears to be a general decline in reactivity of the ARAS with advancing years. Changes in electrical coupling have been suggested to account for some changes in ARAS activity: if coupling were down-regulated, there would be a corresponding decrease in higher-frequency synchronization (gamma band). Conversely, up-regulated electrical coupling would increase synchronization of fast rhythms that could lead to increased arousal and REM sleep drive. Specifically, disruption of the ARAS has been implicated in the following disorders: • Narcolepsy: Lesions along the pedunculopontine (PPN) and laterodorsal tegmental nuclei are associated with narcolepsy. There is a significant down-regulation of PPN output and a loss of orexin peptides, promoting the excessive daytime sleepiness that is characteristic of this disorder. • Parkinson's disease: REM sleep disturbances are common in Parkinson's. It is mainly a dopaminergic disease, but cholinergic nuclei are depleted as well. Degeneration in the ARAS begins early in the disease process. Regardless of birth weight or weeks of gestation, premature birth induces persistent deleterious effects on pre-attentional (arousal and sleep-wake abnormalities), attentional (reaction time and sensory gating), and cortical mechanisms throughout development. • Smoking during pregnancy: Prenatal exposure to cigarette smoke is known to produce lasting arousal, attentional and cognitive deficits in humans. This exposure can induce up-regulation of α4β2 nicotinic receptors on cells of the pedunculopontine nucleus (PPN), resulting in increased tonic activity, resting membrane potential, and hyperpolarization-activated cation current. These major disturbances of the intrinsic membrane properties of PPN neurons result in increased levels of arousal and sensory gating, deficits (demonstrated by a diminished amount of habituation to repeated auditory stimuli). It is hypothesized that these physiological changes may intensify attentional dysregulation later in life. Descending reticulospinal system The reticulospinal tracts, are extrapyramidal motor tracts that descend from the reticular formation in two tracts to act on the motor neurons supplying the trunk and proximal limb flexors and extensors. The reticulospinal tracts are involved mainly in locomotion and postural control, although they do have other functions as well. The descending reticulospinal tracts are one of four major cortical pathways to the spinal cord for musculoskeletal activity. The reticulospinal tracts work with the other three pathways to give a coordinated control of movement, including delicate manipulations. • The medial reticulospinal tract (pontine) is responsible for exciting anti-gravity, extensor muscles. Function • Integrates information from the motor systems to coordinate automatic movements of locomotion and posture • Facilitates and inhibits voluntary movement; influences muscle tone • Mediates autonomic functions • Modulates pain impulses • Influences blood flow to lateral geniculate nucleus of the thalamus. Clinical significance The reticulospinal tracts provide a pathway by which the hypothalamus can control sympathetic thoracolumbar outflow and parasympathetic sacral outflow. Two major descending systems carrying signals from the brainstem and cerebellum to the spinal cord can trigger automatic postural response for balance and orientation: vestibulospinal tracts from the vestibular nuclei and reticulospinal tracts from the pons and medulla. Lesions of these tracts result in profound ataxia and postural instability. 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. Responding to a startling or painful stimulus, both arms and legs extend and turn internally. The cause is the tonic activity of lateral vestibulospinal and reticulospinal tracts stimulating extensor motoneurons without the inhibitions from rubrospinal tract. Brainstem damage above the red nucleus level may cause decorticate rigidity. Responding to a startling or painful stimulus, the arms flex and the legs extend. The cause is the red nucleus, via the rubrospinal tract, counteracting the extensor motorneuron's excitation from the lateral vestibulospinal and reticulospinal tracts. 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. Damage to the medulla below the vestibular nuclei may cause flaccid paralysis, hypotonia, loss of respiratory drive, and quadriplegia. There are no reflexes resembling early stages of spinal shock because of complete loss of activity in the motorneurons, as there is no longer any tonic activity arising from the lateral vestibulospinal and reticulospinal tracts. ==History==

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. The term "reticulum" means "netlike structure", which is what the reticular formation resembles at first glance. It has been described as being either too complex to study or an undifferentiated part of the brain with no organization at all. Eric Kandel describes the reticular formation as being organized in a similar manner to the intermediate gray matter of the spinal cord. This chaotic, loose, and intricate form of organization is what has turned off many researchers from looking farther into this particular area of the brain. The cells lack clear ganglionic boundaries, but do have clear functional organization and distinct cell types. The term "reticular formation" is seldom used anymore except to speak in generalities. Modern scientists usually refer to the individual nuclei that compose the reticular formation. Moruzzi and Magoun first investigated the neural components regulating the brain's sleep-wake mechanisms in 1949. Physiologists had proposed that some structure deep within the brain controlled mental wakefulness and alertness. It had been thought that wakefulness depended only on the direct reception of afferent (sensory) stimuli at the cerebral cortex. 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. He first stimulated the ascending somatic and auditory paths; second, a series of "ascending relays from the reticular formation of the lower brain stem through the midbrain tegmentum, subthalamus and hypothalamus to the internal capsule." ==See also==