Neuroanatomy of the Brainstem Reticular Formation
cytoarchitecture: the delimitation of cell groups or nuclei based on the morphological features of individual cells and on the patterns of their arrangement in the anatomical space. Typically this is studied using Nissl techniques and light microscopy.
Where is it?
The term reticular formation (formatio reticularis or substantia reticularis) was first introduced by anatomists in the early part of this century to designate those parts of the brainstem (medulla pons and midbrain) which are made up of cells having various sizes and shapes, lying scattered within the core of the brainstem and surrounded by a complicated network of fibers running in all directions (Rossi and Zanchetti, 1957).
The brainstem reticular formation is a region within the brainstem core with a complex highly structured pattern of overlapping dendritic fields in the transverse (coronal) plane which arise from several distinct nuclei embedded within the network. It does not include the cranial nerve nuclei, the long tracts that pass through the brainstem nor any of the well defined brainstem nuclei such as the nucleus ambiguus nor the Red nucleus.
The RF has a complex organization but it is not random. There are well defined sub nuclei, well characterized cell types and well organized projections.
What is its structure ?
The cells of the reticular formation show a wide variety of dendritic patterns. These have been characterized into three basic categories.
isodendritic (from isos meaning similar unchanging uniform): These cells are symmetric with dendrites radiating in all directions for large distances which branch out and overlap with neighboring nuclei. Isodendritic cells are the most common and form the core of the reticular formation.
allodendritic (from allos meaning different): These tend to have more specialized shapes and are intermediate between iso- and idio- dendritic
idiodendritic (from idio meaning peculiar): These are the most specialized of all. The dendrites tend to stay entirely within a zone or nucleus.
Cells in the Reticular formation characterized by there relative size:
The largest cells are referred to as giant cells or gigantocellular
The small cells are referred to as parvocellular.
medium to large size cells are referred to as magnocellular
All of these cells are oriented with their dendrites in the coronal plane.
Their axons ascend and descend along the long axis of the brainstem
Ascending axons are carried in the central tegmental tract
Descending axons are carried in the reticulospinal tract
The reticular formation is divided into 4 zones at all levels along the brainstem axis. (see for example Figure 9-1of Barr & Kiernan. Compare the location of the reticular formation with the location of the cranial nerve nuclei shown in Figure 8-15) All these areas are distinguished on the basis of their cytoarchitecture but they are also functionally distinct. In addition a 5th zone is defined in the medulla.
1. The Raphe
Raphe is Greek for seam. These groups of cells lie along the midline of the brainstem. The cells of the raphe are interspersed among the fibers that cross to the other side. They form a continuous column but there are distinct cytoarchitectronic differences and different efferent projections. The raphe nuclei all contain the neurotransmitter serotonin (5-HT) which generally has an inhibitory effect. The projections of these cell groups are widespread and in particular the more rostral nuclei project directly to the cortex. A general rule about raphe projections...The caudal nuclei descend, the rostral nuclei ascend.
2. Paramedian Zone:
The paramedian groups consist of the paramedian reticular nucleus and the pontine reticulotegmental nucleus. They project to the cerebellum and are involved in motor functions.
3. The Medial Zone:
It is located in the medial 2/3 of the tegmentum and is associated with motor functions. The medial zone, in addition to small cells contains giant cells (gigantocellular) that have bifurcating axons that ascend and descend. This forms the major output of the reticular formation and projects to the hypothalamus and thalamus via the central tegmental tract and projects t to the spinal cord via the reticulospinal tract.
4. The Lateral Zone:
It is located in the lateral 1/3 of the tegmentum. It is composed of small (parvocellular) cells that have relatively short ascending and descending axons that terminate primarily within the medial reticular zone. This zone is thought to be an afferent association area because it receives multiple sensory inputs from the spinal cord, cranial nerves and cerebrum.
5. The Intermediate Zone:
This region is found only in the medulla and lies situated between the later zone and medial zone. It is involved in the autonomic regulation of respiration, heart rate and blood pressure.
Subdivisions of the reticular formation by Brainstem region & Functions
The medullary reticular formation consists of three separate regions
1. The paramedian reticular group projects to the cerebellum and is involved in the co-ordination of fine movements It also receives projections from the cerebellum.
2. Nucleus Gigantocellularis gets its name form the giant cells there. It projects mainly to spinal cord. Nucleus Gigantocellularis pars alpha is involved in muscle atonia during REM sleep
3. The lateral reticular group consists of two subdivisions 1) the lateral reticular nucleus 2) the parvocellular nucleus.
4. The intermediate reticular nucleus is involved in the autonomic regulation of respiration, heart rate and blood pressure mediated through bulbospinal pathways.
The pontine reticular formation has two major divisions:
1. Pontis Caudalis continues from the gigantocellular nucleus. It continue to have large cells but they become less prominent.
2. Pontis Oralis starts about the level of Motor trigeminal nucleus and continues to the level of the midbrain. It has no giant cells.
The best known function of the pontine reticular formation is it role in horizontal conjugate eye movements which is mediated by the paramedian pontine reticular formation. It projects to the abducens, n. prepositus hypoglossi and the vestibular nuclei, to the medial rectus motorneurons in the occulomotor nucleus.
One other very important nucleus that you have probably already encountered is the locus coreleus. This nucleus has widespread projections throughout the brain, particularly to cortex and plays a role in arousal and waking. Its cells contains norepinephrine.
The midbrain reticular formation continues through the core of the midbrain tegmentum but is much less extensive than the pons or medulla. There are three nuclei you should be familiar with.
The Cuneiform nucleus and subcuneiform nucleus are involved in motor functions
The pedunculopontine tegmental nucleus sends cholinergic projections to the basal ganglia as well as to every nucleus of the thalamus. It extends from the Pons into the midbrain. This nucleus is also involved in the generation of sleep states.
The Ascending Reticular Activating System
In 1949 the concept of the general function of the reticular formation changed overnight with the publication of a pair of papers (Lindsley et al., 1949; Morruzzi and Magoun, 1949) In these papers the authors proposed that there is a diffuse system of ascending fibers arising in the reticular formation that is responsible for control of states of consciousness. They called their system the ascending reticular activating system (the ARAS).
Please Note: The ARAS is a functional concept. The reticular formation is an anatomical structure.
Modern concepts of the ARAS consider it to be composed of several distinct systems including the cholinergic, noradrenergic and serotonergic. As you will see in an upcoming lecture this is all important in the regulation of cortical function.
Things you should know:
Know the general types of cells (dendritic patterns and sizes) in the brainstem reticular formation and how they are arranged (how are dendrites arranged? How are axons arranged?)
Know the major nuclei and their basic functions
Each of the recommended texts has sections on the reticular formation.
Carpenter is the most detailed with summary for each region of the brainstem
Barr and Kiernan, Chapter 9, give an excellent review of the most important nuclei.
Noback, Strominger and Demerest give a succinct overview of the reticular formation in Chapter 22.
For more depth:
Brodal, A. (1981) Neurological Anatomy: In relation to Clinical Medicine. 3rd Ed. Chapter 6.
Alf Brodal is one of this centuries preeminent experts on the reticular formation. This chapter is very thorough and points to numerous articles regarding the structure and function of the RF.
Rossi, G. F. and Zanchetti, A. (1957). The brainstem reticular formation. Archies Italiennes de Biologie 95:(3-4):203-435. This is an old review but it is very complete,
Ramon-Moliner, E. and Nauta, W. J. H. The isodendritic core of the brainstem. Journal of Comparative Neurology 126:311-336. This is where the three categories of reticular cells were defined.
The following two papers are of historical interest. These papers defined the ARAS.
Morruzzi, G. and Magoun, H. W. (1949). Brain stem reticular formation and activation of the EEG. Electroencephalography and Clinical Neurophysiology 1:455-473.
Lindsley, D. B., Bowden, J. W. and Magounm, H. W. (1949). Effect upon the EEG of acute injury to the brain stem activating system. Electroencephalography and Clinical Neurophysiology 1:475-486.
If you have any questions please do not hesitate to come and talk to me. Thanks.
RM 13 - N4