Reticular formation
The reticular formation is a set of interconnected nuclei in the brainstem that spans from the lower end of the medulla oblongata to the upper end of the midbrain. The neurons of the reticular formation make up a complex set of neural networks in the core of the brainstem. The reticular formation is made up of a diffuse net-like formation of reticular nuclei which is not well-defined. It may be seen as being made up of all the interspersed cells in the brainstem between the more compact and named structures.
The reticular formation is functionally divided into the ascending reticular activating system, ascending pathways to the cerebral cortex, and the descending reticular system, descending pathways to the spinal cord. Due to its extent along the brainstem it may be divided into different areas such as the midbrain reticular formation, the central mesencephalic reticular formation, the pontine reticular formation, the paramedian pontine reticular formation, the dorsolateral pontine reticular formation, and the medullary reticular formation.
Neurons of the ARAS basically act as an on/off switch to the cerebral cortex and hence play a crucial role in regulating wakefulness; behavioral arousal and consciousness are functionally related in the reticular formation using a number of neurotransmitter arousal systems. 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, gigantocellular reticular nuclei, and parvocellular reticular nuclei. 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. It is phylogenetically old and found in lower vertebrates.
Structure
The human reticular formation is composed of almost 100 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
- In the lateral column – parvocellular nuclei
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.Ascending reticular activating system
The ascending reticular activating system, also known as the extrathalamic control modulatory system or simply the reticular activating system, is a set of connected nuclei in the brains of vertebrates that is responsible for regulating wakefulness and sleep-wake transitions. The ARAS is in the midbrain reticular formation. It is mostly composed of various nuclei in the thalamus/hypothalamus and a number of dopaminergic, noradrenergic, serotonergic, histaminergic, cholinergic, and glutamatergic brain nuclei.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 ARAS is a collection of different nuclei – more than 20 on each side in the upper brainstem, the pons, medulla, and posterior hypothalamus. The neurotransmitters that these neurons release include dopamine, norepinephrine, serotonin, histamine, acetylcholine, and glutamate. They exert cortical influence through direct axonal projections and indirect projections through thalamic relays.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 glutamate-releasing neurons in the ARAS were identified much more recently relative to the monoaminergic and cholinergic nuclei; the glutamatergic component of the ARAS includes one nucleus in the hypothalamus and various brainstem nuclei. The orexin neurons of the lateral hypothalamus innervate every component of the ascending reticular activating system and coordinate activity within the entire system.
| Nucleus type | Corresponding nuclei that mediate arousal | Sources |
| Dopaminergic nuclei | ||
| Noradrenergic nuclei | ||
| Serotonergic nuclei | ||
| Histaminergic nuclei | ||
| Cholinergic nuclei | ||
| Glutamatergic nuclei | ||
| Thalamic nuclei |
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.
Function
Consciousness
The ascending reticular activating system is an important enabling factor for the state of consciousness. The ascending system is seen to contribute to wakefulness as characterised by cortical and behavioural arousal.Regulating sleep-wake transitions
The main function of the ARAS is to modify and potentiate thalamic and cortical function such that electroencephalogram desynchronization ensues. There are distinct differences in the brain's electrical activity during periods of wakefulness and sleep: Low voltage fast burst brain waves are associated with wakefulness and REM sleep ; 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. Stimulation of the ARAS produces EEG desynchronization by suppressing slow cortical waves, delta waves, and spindle wave oscillations and by promoting gamma band oscillations.The physiological change from a state of deep sleep to wakefulness is reversible and mediated by the ARAS. The ventrolateral preoptic nucleus of the hypothalamus inhibits the neural circuits responsible for the awake state, and VLPO activation contributes to the sleep onset. 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. Dysfunction of the paraventricular nucleus of the hypothalamus can lead to drowsiness for up to 20 hours per day.