A Brief History of the Reticular Formation
by David D. Olmsted (Copyright - 1998, 2006. Free to use for personal and
Last Revised August 31, 2006
The Reticular Formation in the Cat
Caudal (Tailward) Projections
The reticular formation (RF) began to receive attention
in 1909 with the anatomical brain investigations of Santiago Ramon y Cajal
of Spain. Using the new silver chromate staining method first developed by
Golgi he revealed the shapes of individual neurons for the first time. Because
of his careful work Cajal realized that the brain was composed of individual
cells (neurons) and was not a continuous net (reticulum) of fibers as was
believed by Golgi. Cajal commented on the extensive multiple branchings of the reticular
formation neurons as they ascended and descended through the middle of the brain
stem. Building on some earlier German work, J.W. Papez in 1926 published
a definitive work describing the reticular formation's projections down to the
spinal cord in cats.
Rostal (Headward) Projections
That the reticular formation
had ascending projections to higher brain centers was inferred in 1935 by
F. Bremer of France. He demonstrated that severing the brain from the reticular
formation produced a sleep like state now called a coma which lasted until
the animals died. The early 1940's saw a series of papers published by Morison
and Dempsey (Dempsey, et al -1941), (Morison, et al - 1942a, 1942b) of the
U.S.A. describing the mammalian thalamic projections to the cortex which were under
reticular formation influence and which presumably were responsible for producing
By 1950 researchers were localizing various ascending effects by
lesioning different regions of the reticular formation (see Lindsley, Schreiner,
Knowles, and Magoun, 1950). The conclusion reached by all of these studies
was that the ascending reticular formation signals kept the animal alert and
awake with the result that this projection came to be known as the Ascending Reticular
Activating System of ARAS. Consequently, sleep was assumed to be produced
by a lack of ascending reticular formation signals yet in 1953 this assumption was
challenged by Hess, Koella, and Alcart of Germany who found that sleep could
be produced by stimulating certain sites within the reticular formation.
MotorActions Produced in Animals
The first clue that the reticular formation had an influence
on motor activity was provided in 1946 by Rhines and Magoun of the U.S.A.
Electrical stimulation of the reticular formation in anesthetized cats or
in restrained cats having having their brain stem severed from the rest of
the brain (decerebrate) and thus in a coma produced changes in muscle tone.
The first electrical stimulation studies of the reticular formation in free-moving
unanesthetized can were undertaken by Americans Sprague and Chambers in 1954.
Stimulation at one site in a cat sitting or standing produced the pre-rest
actions of circling and lying down. The lying down ended when the stimulation ended.
Stimulation of another site with the cat initially in a reclining position produced
the action of standing and then circling.
The electrical stimulation experiments
of the mammalian reticular formation by Hess inspired fellow Germans Eric
von Holst and Ursula von Saint-Paul to try the same procedure in chickens
with their report appearing in English in 1961. Since birds do not have a
large cerbral cortex to plan motor actions these experiments more clearly exhibited
the motivation releasing strategy of the reticular formation. In his work on birds
von Holst was following the ethological tradition established by fellow Germans
Konrad Lorentz and Nikolaas Tinbergen who together first developed the concept
of the "Innate releasing mechanism" from their observations of bird behavior.
This concept states that whenever the motivation is the same, a defined set
of stimuli will always release a specific motor response. Lorentz was the
first to propose this concept in a 1935 German paper but not until 1948 and
1951 did Tinbergen introduce this concept to the English speaking world.
Error Criterion Effect and “Winner Take All”
The region of the brain actually stimulated
by von Holst and von Saint-Paul involved the whole motivation system ranging
from the septum to the hypothalamus and down to the reticular formation and
their report does not precisely identify the locations of each stimulation.
Still the error criterion effect of the level of motivation on object triggered
motor actions is clearly shown in one experiment. When a stuffed polecat
(a small predator of chickens) was placed next to an unstimulated rooster the rooster
made no response yet the same stuffed polecat was attacked by the rooster
when its brain was stimulated (page 18). Under strong stimulation the rooster
would even attack the face of the human handler. Notice that these actions
are target directed behaviors and not simply inflexible reflexive behaviors.
Often a sequence of actions could be produced by gradually increasing the
level of the stimulation. One sequence begins with the chicken exhibiting
"fear" as indicated by its rapidly looking about and progressing to clucking,
standing, walking around or defecating, and finally flight. Instead if the
stimulation is suddenly increased to maximum the chicken will abruptly fly
off screaming (page 16).
Their stimulation of two sites simultaneously shows that
the strongest stimulation gains access to the motor actions. Stimulation of
one of these sites produced the escape sequence of standing, walking about,
and then jumping off a ledge while stimulation of the other site produced
a sitting action. Simultaneous activation of these sites resulted in the sitting
action but gradually increasing the stimulation of the escape sequence site
resulted in the chicken suddenly jumping off the ledge (page 16).
The early 1960's
produced more information about the reticular formation's inputs in mammals.
These advances were based upon the nerve degeneration method in which the
cell body is destroyed leading the the degeneration of it axon which can then be
stained and observed. The major inputs originated from the spinal cord (body state
information), the solitary complex (gasto-intestinal information), vetibular nuclei
(balance and motion information), and the trigeminal nuclei (body state information
from the head and neck). (See Brodal & Rossi, 1955; and Valverde, 1961). Another
major input to the reticular formation originated in the tectum which provides
visual, auditory, and tactile pattern information (Altman and Carpenter, 1961).
A smaller input arrives from the fastigial nucleus of the cerebellum (Walbery,
et al, 1962)
Simple Brain Connections
Not until later were the reticular formation
connections in non-mammals investigated. In the late 1960's the tectum projections
to the reticular formation were confirmed in a wide variety on non-mammals
(see Foster and Hall, 1975, for references). Yet not until the late 1980's
were the descending reticular projections to the spinal cord confirmed (see
Prasada, Jadhao, and Sharma, 1987, for references). The ascending reticular
formation projections to the thalamus have only been found in reptiles (see ten
Donkelaar and de Boar-van Huizen, 1981).
Yet even better neural axon tracing
methods were needed before projections from the hypothalamus were reported
in 1981 with the publication of a paper by Morrell, Greenberger, and Pfaff.
This work relied upon methods developed during the mid 1970s which used special
dyes which are taken up by neurons and transported down their axons. Discovering
these projections using axon degeneration methods would have required massive
destruction of the hypothalamus which in turn would have killed the animal.
Yeteven as early as 1968 hints existed for a hypothalamic projection to the reticular
formation. The posterior hypothalamus (the end of the hypothalamus nearest to
the reticular formation) was shown to be required for avoidance types of operant
conditioning. American Quentin Registein destroyed the posterior hypothalamus on
only one side of a fish previously trained to escape from a square image of
black dots in order to avoid a shock. When the square was presented to the
eye on the side opposite that of the destroyed hypothalamus (the optical path from
the eyes cross over to the opposite side of the brain) the fish either didn't
respond or responded only very slowly.
In 1967 M.E. Scheibel and A.B. Scheibel produced
the now classic pictures of the neural structure of the reticular formation.
Their suggested functions of the reticular formation were:
of operational modes, gating mechanism for all sensory influx, modulation
and monitor of cortical function, readout mechanism for cortical differentiative
and comparative processes, and gain manipulator for motor output."
conclusions were little changed in a 1984 review by A.B. Scheibel.
The First Reticular Formation Model
Using the anatomical data from the Scheibels, W.L. Kilmer, W.S.
McCulloch, and J. Blum presented several papers on their Difference
Enhancement Models of the reticular formation (S-RETIC and STC-RETIC) which
culminated in their 1969 paper coinciding with the end of the first phase
of interest in neural networks. While their models have many problems their view
of the reticular formation as an animal's central command system was accurate
as shown by this excerpt:
"No animal can, for instance, fight, go to sleep,
run away, and make love all at once. We have listed as mutually incompatible
modes of vertebrate behavior:
- hunt (for prey or
- search (or explore)
- mate (or sex)
- give birth (or
- mother the young (including suckling or hatching, retrieval, perineal
licking, and so on)
- build or locate a nest
- and special innate forms of behavior
such as migrate, hibernate, gnaw, and hoard, depending on the species
Some may challenge this particular list, but the point is that there are not more
than about 25 such modes. An animal is said to be in a mode if the main focus
of attention throughout it central nervous (CNS) is on doing the things of that
mode. We hypothesize that the core of the reticular formation (RF) is the structure
in vertebrates that commits the animal to one or another mode of behavior.
In 1973 the reticular formation region called the Mesencephalic Locomotor
Region (MLR) responsible for releasing locomotion actions in the cat was found by
Grillner and Shik of the U.S.S.R. It is located just below the auditory tectum
(inferior coliculus in mammals). After severing the brain stem just behind
the hypothalamus to prevent interfering signals from entering the reticular
formation stimulation of the MLR always produced a locomotor action. If a
part of the hypothalamus in included in with the reticular formation then
spontaneous locomotion actions and other actions are observed. If instead
if the cut is made lower in the reticular formation below the red nucleus then no
amount of stimulation of the MLR will produce locomotion suggesting that body state
information is blocking the triggering signal. Since the red nucleus receives most
of its inputs from the cerebellum it very likely is responsible for modulating
these body state signals. After all, the body must be in an upright posture
before walking to begin or in a state which the cerebellum can transform to
an upright posture.
The 1970's saw the introduction of micro-electrodes capable
of recording the activity of single cells. These studies found that most cells
of the reticular formation were responsive in some way to sensory stimulation
yet they also found that the activity of the cells correlated best with motor
activity (see Siegel and McGinty, 1977). A few tonically active cells were
also found which increased their firing rate in response to sound or light
stimuli associated with a shock in a classical conditioning situation (Vertes
and Miller, 1976).
Altman, J. and Carpenter, M.B. (1961). Fiber Projections
of the Superior Colliculus in the Cat. Journal of Comparative Neurology 116:157-178
Bremer, F. (1935) Cerveau "isole" et Physiologie du Sommeil. C.R. Soc. Biol.
Brodal, A. and Rossi, G. (1955) Ascending Fibers in Brain Stem
Reticular Formation of Cat. Arch. Neurol. Psychiatry 74:68-87
Dempsey, E.W., Morison,
R.S. and Morison, B.R. (1941) Some Afferent Diencephalic Pathways related
to Cortical Potentials in the Cat. American Journal of Physiology 131:718-731
Grillnew, S. and Shik, M.L. (1973) On the Descending control of the Lumbrosacral
Spinal cord from the "Mesencephalic Locomotor Region" Acta Physiol. Scnd.
Hess Jr. R., Koella, W.P. and Alcart, K. (1953) Cortical and Subcortical
Recordings in Natural and Artificially Indiced Sleep in Cats. Electroencephalogr.
Clin. Neurophysiol. 5:75-90
Kilmer, W.L., McCulloch, W.S., Blum, J. (1969) A Model
of the Vertebrate Central Command System. International Journal of Man-Machine
Studies 1: 279-309
Lindsley, D.B., Schreiner, L.H., Knowles, W.B., and Magoun,
W. (1950) Behavioral and EEG Changes following chronic Brain Stem Lesions
in the Cat. Electroencephalogr. Clin. Neurophysiol. 2:483-498
(1935) Der Kumpan in der Umwelt des Vogels. Der Artgenosse als auslosendes
moment sozialer Verhaltensweisen. Journal fur Tierpsychologie 5:235-409
H.W. and Rhines, R. (1946) An Inhibitory Mechanism in the& bulbar Reticular
Formation. Journal of Neurophysiology 9:165-171
Morison, R.S. and Dempsey, E.W.
(1942a) A Study of Thalamo-cortical Relations. American Journal of Physiology
Morison, R.S. and Dempsey, E.W. (1942b) Mechanism of Thalamo-cortical
Augmentation and Repetition. American Journal of Physiology 138:297-308
J.I., Greenburger, L.M., and Pfaff, D.W. (1981) Hypothalamic, other Diencephalic
and Telencephalic Neurons that Project to the Dorsal Mid-brain. Journal of
Comparative Neurology 41:365-399
Papez, J.W. (1926) Reticulo-spinal Tracts in the
Cat, Marchi Method. Journal of Comparative Neurology 41:365-399
P.D., Jadhao, A.G., and Sharma, S.C. (1987) Descending Projection Neurons
to the Spinal Cord of the Goldfish, Carassius auratus. Journal of Comparative
Ramon y Cajal, S. (1909, 1911) Histologie du Systeme Nerveux
de L'homme et des Vertebres Maloine, Paris; volumes 1 and 2
Regestein, Q.R, (1968)
some Monocular Emotional Effects of Unilateral Hypothalamic Lesion in Goldfish,
pages 139-144 in The Central Nervous System and Fish Behavior, edited by David
Ingle; University of Chicago Press, Chicago, IL
Rhines, R. and Magoun, H.W.
(1946) Brain Stem Facilitation of cortical Motor Responses. Journal of Neurophysiology
Scheibel, M.E. and Scheibel, A.B. (1967) Anatomical Basis of Attention
Mechanisms in Vertebrate Brains, Pages 577-602 in The Neurosciences: A Study
Program, edited by G.C. Quarton, T. Melnechuk and F.O. Schmitt; Rockefeller
University Press, New York
Schiebel, A.B. (1984) The Brain Stem Reticular Core and
Sensory Function, pages 213-256 in Handbook of Physiology; the Nervous System
volume 3, part 1, edited by S.R. Gieger; American Physiological Society, Bethesda,
Siegal, J.M. and McGinty, D.J. (1977) Pontine Reticular Formation Neurons:Relationship
of Discharge to Motor Activity. Science 196:678-680
Sprague, J.M. and Chambers,
W.W. (1954) Control of Posture by Reticular Formation and Cerebellum in the
Intact, Anesthetized and Unanesthetized and in the Decerebrated Cat. American
Journal of Physiology. 17652-64
ten Donkelaar, H.J and de Boer-van Huizen, R. (1981b)
ascending Projection of the Brainstem Reticular Formation in a Non-mammalian
Vertebrate (the Lizard Varanus exanthematicus) with Notes on the Afferent
Connection of the Forebrain. Journal of Comparative Neurology 200:501-528
Tinbergen, N. (1948) Social Releasers and the Experimental Method Required
for Their Study. Wilson Bulletin 60:6-52
Tinbergen, N. (1951) The Study of Instinct.
Clarendon Press Valverde, F. (1961) Reticular Formation of the Pons and Medulla
Oblongata. A golgi Study. Journal of Comparative Neurology 116:71-99
and Miller, N.E. (1976) Brain Stem Neurons that Fire Selectively to a Conditioned
Stimulus for Shock. Brain Research 103:229-242
von Holst, E. and von Saint-Paul,
U. (1961) On the Functional Organization of Drives. Animal Behavior 11:1-20
Walberg, F., Pompeiano, O., Westrum, L.E. and Hauglie-Hanssen E. (1962) Fastigioreticular
Fibers in Cat. An Experimental Study with Silver Methods. Journal of Comparative