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And as William James emphasized, concerned is not a search for liaison between brain as a
even a consciously learned response can become so physical instrument and some other entity which is mind.
habituated that it submerges to the non-conscious level What we must do is to discover those characteristics of
and thereafter is taken care of quite automatically by the brain as living tissue which enable it to have as one of its
nervous system, more or less on the same plane as genet- own intrinsic physicalistic properties the awareness that
ically endowed behavior. we call mind. . . . What we need here is more knowledge
Perception, memory, learning, and consciousness are of the actual structure and operation of the nervous mech-
all biological activities of the nervous system. As Herrick anisms that do the thinking."55
remarked: "The problem with which science is properly
A COMPLEX OF neurons and fibers that constitute the most Historical resume
primitive part of the brain wanders through the substance
of the brain stem. This archaic system shows little evidence "It is known from embryology that most of the leftover
cells of the brain stem and spinal cord which are not con-
of rigid structure, and approaches, in some respects, the
cerned in the formation of motor root nuclei and purely
communication engineer's ideal of the statistical net. We sensory relay nuclei are utilized in the production of the
cannot call this reticular formation truly isotropic, but here formatio reticularis." In this curiously negative manner
one can find no hint of the columnar arrays of cortical commences a short and prescient article by W. F. Allen,'
pyramids, the file-on-file of bidimensional Purkinje cells published in 1932, which sketched out an envelope of
of cerebellum, nor even the whorled clusters of sensory functional roles for the brain-stem reticular core that was
field cells, such as characterize analogically mapping fields to be followed by investigators for the next three decades.
of sensory relays. But the tenor of the sentence also reflects almost a century
But perhaps as a result of this muted statement of its of neurological prejudice, which conceived the reticular
structural theme, there resides within the brain-stem core of the brain stem largely as filler—a kind of neuro-
core a remarkable pluripotentium of functional roles that ectodermally derived excelsior, in which were cushioned
have become increasingly obvious over the past quarter the more functionally attractive cranial nerve nuclei.
century and that probably mark it as the most critical During the past quarter century, there has been a dra-
integrative center of the brain—determiner of operational matic change in value judgments. Compared to the spec-
modes, gating mechanism for all sensory influx, modulator trum of presently recognized reticular functions, ranging
and monitor of cortical function, readout mechanism for from homeostat operations practiced on the internal mi-
the cortical differentiative and comparative processes and lieu to modulation and control of highest psychic func-
gain manipulator for motor output. A brief, tions, the workings of cranial nerve nuclei seem almost
chronologically oriented survey of the development of our humdrum. If our appreciation of the astonishing range of
thoughts about this multi-faceted system may prove physiological possibilities inherent in the core seems a
useful in gaining insight into its present stature. strictly contemporary phenomenon, it was not necessary
that it be so, for the anatomical and physiological litera-
M. E. SCHEIBEL AND A. B. SCHEIBEL Departments of
ture has been replete with clues pointing in these directions
Anatomy and Psychiatry and Brain Research Institute, UCLA, since the turn of the century.
Medical Center, Los Angeles, California Anatomical studies of Kohnstamm and Quensel,2,3
FIGURE 1 Schematic representation of the relations of the and associated structures, on spinal cord (long, downward-
reticular core of the brain stem (black) with other systems of directed arrow), and on central sensory relays (striped ar-
the brain. Collaterals pour in from long sensory and motor rows). (From F. Worden, and R. Livingstone, 1961. Brain
tracts (thin lines) and from the cerebral hemispheres (arrows stem reticular formation, in Electrical Stimulation of the
directed downward into reticular core). The core acts in turn Brain [D. Sheer, editor], Univ. of Texas Press, Austin, pp.
on cerebral and cerebellar cortices (upward-directed arrows) 263-276.)
these studies were expanded by Jasper and his associates."-" who have been able to relate the size of sensory evoked
who defined in greater detail the probable anatomical potentials to the focus of active interest momentarily ex-
paths and electrophysiological characteristics of this sys- pressed by implanted, freely mobile animal. Our own
tem. An interpretative capstone was placed on this grow- Golgi investigations33,47 have revealed a suitable substrate in
ing body of data with the suggestion by Penfield22 that the the penetration of most first- and second-order sensory
diencephalic intralaminar system might well serve as a " stations by reticular collaterals. Notwithstanding a recent
centrencephalon" for all neural activity. The classical disclaimer by Worden and Marsh,'" it is generally con-
teachings ofHughlings Jackson23 as to the ultimate status of ceded that, aside from modulation of tonic and phasic
the cerebral cortex in the neuraxial hierarchy was thus components that comprise the activated state,'" the reticu-
supplanted. It had now become penultimate to the upper lar core mediates specific delimitation of the focus of con-
end of the reticular core, and the principle of thalamo- sciousness with concordant suppression of those sensory
cortico-thalamic circulation already proposed by Cajal,' inputs that have been temporarily relegated to a secondary
Campion," and by Dusser de Barenne and McCulloch25 role.
gained support and experimental verification. Knowledge of the intimate physiology of the core has
In the meantime, the range of autonomic control exert- been gleaned from extracellular microelectrode studies by
ed by brain-stem reticular mechanisms had been investi- a number of investigators,'°-52 and most recently by a
gated by Ranson and his colleagues,26.27 thereby extending limited number of intracellular analyses34,53," that have
the work of early investigators in this area, and culminat- examined in some detail the problems of convergence of
ing in concepts of overlapping medullo-pontine fields sub- sensory signals, habituation (response attenuation) of in-
serving respiratory and circulatory patterns. Out of this dividual units to iterative stimuli,55.56 and a cyclical alter-
developed the observations of Magoun and Rhines28-3° on nation of unit sensitivity to the stimulus array.57 At the
brain-stem reticular override (inhibition and facilitation) same time, a group of Golgi studies has revealed much
of ongoing spinal motor activity, with subsequent con- about the relevant substrate,33,58-" and in providing circuit
ceptual modifications by Sprague and Chambers." Short- paradigms for a system with this order of functional com-
ly thereafter followed the epochal report of Moruzzi and plexity, has also suggested program modes applicable to
Magoun,32 describing reticular control over cortical ac- computer design.62
tivity and its relation to the spectrum of conscious states
from attentive awareness to deep sleep. These workers at-
tributed such effects to ascending polysynaptic conduction The core as a mosaic
over successive chains of short-axoned cells. That these
phenomena, in reality, depended importantly on high- In the tradition of the great cortical cytoarchitectonicists (
priority conduction in oligosynaptic and, in some cases, i.e., Brodmann," the Vogts," von Economo," etc.), a
monosynaptic channels to cortex was suggested by our number of attempts have been made to subdivide the re-
Golgi studies33 and more recently by intracellular analyses ticular core of the brain stem into component nuclei on
NV
C.
Tr.sP. 8
T.
N.mes.V-
10
p.Br N.r.I-
N.e e-
Tros
VP
N.Ir.sp.V
N.XII caudal
FIGURE 2 A series of equally spaced drawings of transverse group m of Meesen and Olszewski; N. ic., Nucleus inter-
Nissl-stained sections through the brain stem of the cat to calatus ; N. in., Nucleus interpositus; N. r. 1., Lateral reticu-
show the grouping of cells in the reticular core. Various- lar nucleus; N. r. p., Nucleus reticularis paramedianus ;
sized dots on the right indicate specific cell bodies, while N. r. t., Nucleus reticularis tegmenti pontis; N. t. d., Dorsal
dotted lines on the left indicate approximate boundaries of tegmental nucleus; N. t. v., Ventral tegmental nucleus;
major reticular nuclei. Terminology and nuclear areas are P. g. Periaqueductal gray; P. h., Nucleus prepositus hypo-
based on the studies of Olszewski in the rabbit, with minor glossi ; R. gc., Nucleus reticularis giganto-cellularis ;
modifications. The following list of abbreviations refer Nucleus reticularis lateralis (of Meesen and Olszewski); R .
only to structures making up the reticular core: a, mes, Reticular formation of mesencephalon; R.n., Nucleus
Accessory group of paramedian reticular nucleus: d, Dorsal of the raphe; R.p.c., Nucleus reticularis parvocellularis ; R.
group of paramedian reticular nucleus; h, region poor in p.o., Nucleus reticularis pontis oralis ; R.v., Nucleus
cells of Meesen and Olszewski surrounding motor reticularis ventralis; v, Ventral group of paramedian reticu-
trigeminal nucleus; k, cell group k of Mecsen and lar nucleus. (From Brodal, Note 80)
Olszewski; in, cell
tional pattern has recently been exploited by Kilmer and that samples a limited and idiosyncratic fraction of the
McCulloch,62 who have used it as a paradigm for a new total reticular afferent supply, we might pause to con-
generation of computers, which will show increased de- sider the relative significance of neuronal soma and den-
grees of flexibility in dealing with data influx, will habitu- drite, respectively, in servicing the presynaptic array. The
ate over time to iterative stimuli, etc. Although the con- widely ranging dendritic apparatus has already been seen
cept of a reticular core made up of a subinfinite number of to penetrate areas rather remote from that of the parent cell
modules as numerous as its cellular complement may seem body, in quest of presynaptic excitation. We have suggested
overly divisive, it shows a rather good conceptual fit with elsewhere that the dendrites appear to point toward, and
ideas emerging from single-unit analysis of the structure 5°_52 reach for, potent sources of influx, which suggests that
As we will stress again, most neurons appear to receive trophic or neurobiotactic forces are operant during the de-
upon their soma-dendrite surfaces an appreciable, but not velopmental phase. We have previously shown evidence
unlimited, convergent sampling of the many inputs af- of clear-cut segregation of afferent terminals on various
ferent to the core. Each neuron receives its own idiosyn- portions of dendrite shafts in cortex" and on spinal inter-
cratic mix—in terms of afferent selection and loading— neurons." Although we do not have evidence of concen-
from the total influx, so it has seemed appropriate to some trated afferent terminal populations on various portions of
of us52 to consider each neuron as an integrating subcenter, single reticular dendrites, there seems little doubt that
operating upon its own peculiar combination of afferents. many reticular cell dendrites will show marked predomi-
The sum of these neuronal subcenters would, in turn, nance of inputs, depending on the location of that shaft
make up the total mosaic of the operating reticular core, relative to the spectrum of afferent sources (Figure 5).
in which each element performed operations upon one Thus, for a cell located in the ventral-lateral quadrant of
segment of the total envelope. medulla, it might be appropriate to refer to shafts that are
If we accept each reticular element as one of a family predominantly cortico-spinal loaded, spin-thalamic load-
ed, descending trigeminal loaded, etc., thereby emphasiz- states for each major dendrite shaft of a specific reticular-
ing the predominant population of afferents to be found core neuron would represent (with additions from the
on that process. somal synaptic scale) the level of synaptic drive being ap-
However, this concept suffers some dilution because plied to the soma—initial segment at a specific point in
each reticular cell lies in a matrix of fibers, largely (al- time.
though not entirely) core derived and projecting for vary- It seems beyond question that the output of each reticu-
ing distances in the rostro-caudal (and occasionally trans- lar element represents a vector of this type; it therefore
verse) direction. It is a characteristic property of such follows that specific informational content, intrinsic to each of
axons to give off collaterals at right angles more or less the afferent sources, is lost in the integrative process. The out-
continuously along their path.33,60 These collaterals make put of each unit must represent intensity only. It may not
up a spectrum of lengths; some constitute little more than be out of place to suggest the analogy that a major func-
minimal specializations of the fiber in transit (boutons-en- tion of the core is to describe not the pageantry and color
passage). Each reticular dendrite must thread among the of the passing parade, but the loudness of the shouting that
paths of tens of thousands of such axons, so a considerable accompanies it.
number of axodendritic contacts must be expected from
this source, even if mere contiguity of nonspecialized axon The presypnatic influx
conductors with dendritic membrane is not in itself suffi-
cient for information transfer. It seems logical to expand The reticular core of the brain stem may be thought of as
the hypothesis of sensory-annotated dendritic monads to sitting athwart all incoming and outgoing information-
include in each case a sprinkling of core-derived afferents. carrying systems. The collaterals and terminals that pour
The moment-to-moment dendritic membrane loading in at every level receive a continuous stream of samples of
would thereby represent an integrate of specific and non- the activity ongoing in these tracts. In general, archaic af-
specific inputs. In turn, the algebraic summation of such ferent and efferent systems, like the spino-thalamics and
extrapyramidals, are more thoroughly represented than dude: (1) fibers from more rostrally placed centers (cere-
the phylogenetically newer tracts, such as the dorsal col- bral cortex, basal ganglia, diencephalon, and limbic or al-
umn—medial lemniscus and pyramid. The former (medial locortex) ; (2) fibers ascending from the spinal cord; (3) fi-
lemniscus), in fact, probably contributes no collaterals to bers originating in the cerebellum and other brain-stem
the core, thus suggesting that information with a high de- structures such as the geniculate bodies, colliculi, etc.
gree of locus and mode specificity is not crucial to the op- These data are discussed in comprehensive form in several
eration of the reticular mosaic. places.79,80 Accordingly, only a few summarizing state-
A fairly massive spino-reticular system introduces af- ments will be made here.
ferent activity into medullo-pontine levels, along the long
axis of the tract, as do descending components in the cen- THE CORTICO-RETICULAR PROJECTION This makes up
tral tegmental fasciculus and the brachia efferent from the most dramatic, if not the largest, descending system.
cerebellum. The most consistent afferent source, however, The fibers originate in an area centering on the sensor-
appears to be the collaterals that pour in from sagittally motor strip, but extend rather widely into adjacent corti-
coursing fillets along the ventral and lateral aspects of the cal areas, and terminate in "nucleus reticularis giganto-cel-
stem and on each side of midline.5,33 In general, the ag- lularis, more rostally than caudally, while the pontine ter-
gregate of reticulopetal fibers (fibers afferent to the reticu- minal region is found in the nucleus reticularis pontis oralis
lar core) may be divided into several categories, which in- and the nucleus reticularis pontis caudalis, chiefly in its
Ii \
\ /
\ / 1./ /
1
Tr. Pyr.
FIGURE 6 Transverse section through the upper third of Periventr. desc.); vestibulo-reticular fibers (Vestib. retic.) ;
the medulla ofa 10-day-old kitten, showing the convergence the uncinate fasciculus from cerebellum (f. Unc.) ; the tract
and overlapping of terminating afferent fibers in the reticu- of the descending fifth nerve (Tr. V desc.); lemniscus spinalis (
lar core. On the left, a small group of fibers are drawn di- spinothalamic tract) (lernn. spin.); pyramidal tract (Tr.
rectly from the microscope; on the right, as a group of Pyr.); and midline white matter, including medial reticulo- 3,4
overlapping sectors. Reading clockwise from the top, the spinal fibers (T. Rs. med., etc.). (From Scheibel and Scheibel,
afferents include the descending periventricular system (Tr. Note 33)
which we were able to record for periods of from 10 to 12 subsynaptic mosaic (see notes 88 and 89 for empirical data
hours each, there was a succession of reactive phases dur- of possible relevance to this problem). An alternative sug-
ing which the cells appeared alternately sensitive to sen- gestion regarding mechanisms is the presence of a popula-
sory bombardment from the external milieu (mild sciatic tion of pacemaker neurons that controls postsynaptic re-
shocks of 1 to 2 volts of M millisecond, administered at 1- sponse either through presynaptic manipulation90,91 or via
per-second frequency) and from the internal milieu, as interaction of satellite oligoglia, which we have shown re-
exemplified by rhythms following the respiratory cycle. ceive terminating collaterals from the same preterminals
During these respiration-sensitive periods, the reticular that innervate the neuron.92 Each suggestion carries with it
elements were completely refractory to exteroceptive its own intrinsic problems, the most intriguing of which
stimuli (Figure 8). Similarly, during sciatic shock sensitive endow our speculations on the pacemaker.
phases, no traces of interoceptive-modeled activity were In a cellular matrix as complex as the reticular forma--'
ever seen. Each cell seemed to follow a unique temporal tion, if one hypothesizes a pacemaker elite that comprises a;,
pattern within a general order of magnitude of M to 3 fraction of the mass of followers, the quest for order sug-
hours (Figure 9). There was no discernible relation of these gests a hyper-elite to pace the pacemakers, and so on to the
swings to sleep-wakefulness cycles nor were there indica- ultimate absurdity of one supreme, pontifical neuron. At
tions of general physiological changes serving as substrate more attractive variant of this hypothesis involves mobile a
to the alterations. nd redundant command, which temporarily vests pacin
Speculation on the mechanisms underlying this phe- activities on those local arrays whose information loadin
nomenon include hypothecated endocellular rhythms, is of a more biologically urgent nature than that of ado
which periodically change the receptive sensitivities of the jacent, more indecisive domains. As this content-mosai
varies through each fraction of time, it might be resona the reticular net. It may well be that without periodic in-
ble to expect that centers of pacemaking activity would shift put gating of this sort, masses of reticular elements would
widely through the core—a suggestion not out of context gradually be drawn into the full-time service of that sys-
with our own data already mentioned, which indicates tem, sensory or motor, within whose geographic domain
multi-modal operations of reticular elements. they most nearly fall. It is conceivable that by such a proc-
If we assume that the relatively small fraction of reticul ess of gradual acquisition and entrapment, increasing num-
ar elements from which we have led potentials is repres bers of reticular elements would be lost to that range of
entative of the entire array, and that periodically the ma- multi-potent functions that characterize core operations. A
jority of brain-stem-core neurons lower their threshold to neural ensemble, previously free to engage in multi-modal
inputs, first of one sort and then of another, the significance integrative operations, could then conceivably become a
of such behavior becomes a matter of some concern. We crazy quilt of satraps, each one only an extension of the
can only speculate that the cyclic activity which seems to specific system demanding its fealty. Make break swings
-
couple and uncouple neural elements from one circuit or of the sort we have described might effectively counter
another may help preserve functional isotropicity within such a trend.
sa
it
Nt.d.
.
—F.I.m.
N.11
N.r.t.
j
i,
01
N.f.c.
N.c.e.
T.s.
N.m.X
Tr.spV
N.X1I
01.1
F I G U R E 1 0 A lesion at the meso-diencephalic junction of ticularis tegmenti; C.i., inferior colliculus; N. mes. V,
cat brain stem and the position of cell bodies originally send- mesencephalic root of the fifth nerve; N.t.d., dorsal teg-
ing rostral-coursing axons through the site as determined by mental nucleus; N.1.1., nucleus of lateral lemniscus ; VI, sixth
retrograde techniques (see text). Notice that a predominantly nerve nucleus ; N VII, seventh nerve; N.n.V, sensory
unilateral lesion results in degenerating cell bodies (dots) on trigeminal nucleus; N.c., cochlear nucleus; 01.s., superior
both sides of the stem more caudally, and as far posteriorly olive; P.h., perihypoglossal nucleus; N.f.c., cuneate nu-
as the middle third of the medulla. S.n., substantia nigra ; cleus; N.c.e., external cuneate nucleus; T.s., solitary tract
III, third nerve nucleus and nerve; Elm., medial longitudi- and nucleus; N.m.X, motor tenth nerve nucleus (Vagus);
nal fasciculus; N.r., nucleus ruber ; P, pons; C. s., superior Tr. sp. V., descending trigeminal tract and nucleus; N. XII,
colliculus; IV, fourth nerve nucleus; N.r.t., nucleus re- twelfth nerve; 01.i., inferior olive. (From Brodal, Note 80)
• I • .•
1 • •
••
• 1 •
1•.
•
• -Bs
••••••••
••••
CM
FIGURE 11 Distribution of reticular cells sending axons rostrad (
left) and caudad (right) is indicated in two semi-schematic sagit-
tal sections of brain stem of cat. Although there is a good deal of
overlapping, caudally directed axons appear to arise somewhat
more rostral than rostrally directed fibers. The arrows at the side
• : ••• •• •
of the figures indicate that all axon systems are both crossed and -
*:
I s se.
•• • . • ".
uncrossed, except fibers descending from pons, which are un-
crossed. Abbreviations as in previous figures. (From Brodal,
• • •
• /I I'
as.7• MI
Note 80)
••• .. 8
.. • • • • N, •••:*.;.• ...
•■■■•••■• . ••• 8
*..... • OM • •• .. •
•• ••• ``- •••• • o• • ••
discriminate mingling together of rostral- and caudal- •••••••
•
FIGURE 1 3 Sagittal section of an entire mouse brain (7 days tectum, Pt. Other abbreviations include CM, centre me-
old) showing 2 reticular cells in the magnocellular nucleus dian; LP, lateral posterior; LG, lateral geniculate; LD,
of rostral medulla. Both cells emit axons that bifurcate and lateral dorsal; CL, central lateral; AV, anterior ventral; V,
course rostrad and caudad. A number of collaterals are given ventral complex; VA, ventral anterior; R , nucleus reticu-
off by each axon, some of which reach cranial nerve nuclei, laris thalami; ZI, zona incerta; and SN, substantia nigra. (
such as Deiter's component of the vestibular complex, n.D.; From Scheibel and Scheibel, Note 33)
both inferior and superior colliculi, I.C. and S.C.; and pre-
have suggested to us that, on the average, each reticular apposed membranes. However, the presence of trans-
axon releases one collateral of approximately 100-micron membranal electrogenic effects has been shown to exist at
length for each 100 microns of trajectory." This does not least in invertebrates,96.97 and Nelson and Frank have
include large numbers of smaller, bulb-like enlargements mapped a considerable field effect around spinal motoneu-
along the course of the axon, called by Cajal boutons-en-- rons in the cat." Pending more rigorous analysis with re-
passage5 and representing, according to electron-micro- cording techniques of higher resolution, no definitive
graphic analysis, centers especially rich in mitochondria statements can be made about the presence or absence of a
and other intra-axonal organelles. spectrum of field interactions and threshold manipulatory
The picture that emerges is one of continuous, intensive effects in a dense complex of long conductors and axoden-
interaction between large numbers of conductors and the dritic neuropil such as the reticular core.
surrounding matrix of core neurons. The nature of these However, the patterns of connectivity that can be traced
contacts must vary, depending on the presence or absence out through the core suggest a circuit scheme so richly
of a myelin sheath and the frequency of axonal specializa- redundant that convincing arguments could be advanced
tions. No definite statement can be made about the func- for almost any conceivable loop or chain. Figure 15 sum-
tional significance of the untold numbers of contacts es- marizes three alternatives. The first depends largely on
tablished among structures without discernible axonal (or polysynaptic chains of short-axon elements similar to the
postsynaptic) specialization. It is currently fashionable to scheme originally suggested by Moruzzi and Magoun.22
discount the significance of such membrane appositions as The second illustrates the collateral-rich, long-projecting,
seen in electron micrographs if there is no evidence of high-priority axon now known to characterize many re-
membrane thickening, increased opacity to the electron t i c u l a r
neurons. The third combines a group of these, geo-
beam, or presence of synaptic vesicles behind one of the graphically staggered, so that each is activated somewhat
\\
\ k- Fr.
*N-cp
Hp
•
I• 4 3 2 3 4 $ • 1 • • • 7 • r 4 s 0! 3 4 f
\ ss
1 1 7 • 1 1
A,10\
Fr. 6.0
Fr. 7.5 vs • " s \
'
\
\
\
s\
\ % •
•
•\'` . \ \ ' ‘ \ \ \
GM
I H•
Ped; SN
FIGURE 16 The electrophysiologically determined limits of cleus ; mc, pars magnocellularis ; MD, medial dorsal nucleus;
the nonspecific (reticular) system of the thalamus. AD, an- MFB, medial forebrain bundle; NCM, central medial nu-
tero-dorsal nucleus; aHd, dorsal hypothalamic area; AL, cleus; NCP, posterior commissural nucleus; NR, red nu-
ansa lenticularis; AM, antero-medial nucleus; AV, antero- cleus; P, posterior nucleus; Pc, paracentral nucleus; Ped,
ventral nucleus; BC1, brachium of the inferior colliculus ; cerebral peduncle; Prt, praetectum; Pt, parataenial nucleus;
CC, corpus callosum; Cd, caudate nucleus; Cl, claustrum ; Pul, pulvinar ; PVA, anterior periventricular nucleus; PVH,
CL, central lateral nucleus ; CM, centre median nucleus ; CP, periventricular hypothalamic nucleus; R, reticular nucleus;
posterior coinmissure; Da, nucleus of Darkschewitsch; En, RE, nucleus reuniens ; S, medullary stria; SG, supragenicular
entopeduncular nucleus; Fil, filiform nucleus; fsc, subcallo- nucleus; Sm, submedian nucleus; SN, substantia nigra ; Spf,
sal fasciculus; FT, thalamic fasciculus; Fx, fornix; GC, cen- subparafascicular nucleus; ST, terminal stria; THP, habenu-
tral gray matter; GM, medial geniculate body; HbL, lateral lopeduncular tract; TMT, mammillothalamic tract; TO,
habenular nucleus; HbM, medial habenular nucleus; Hi, optic tract; 'FTC, central tegmental tract; VA, ventral an-
field of Fore1; HL, lateral hypothalamus; Hp, posterior hy- terior nucleus; VL, ventral lateral nucleus; VM, ventral me-
pothalamus; IAM, interanteromedial nucleus; IP, inter- dial nucleus; VPL, ventral posterolateral nucleus; VPM,
peduncular nucleus; Is, interstitial nucleus; LD, lateral ventral posteromedial nucleus; ZI, zona incerta. (Figure and
dorsal nucleus; Lim, nucleus limitans; LM, medial caption from Jasper, Note 100)
lemniscus ; LME, external medullary lamina; LP, lateral
posterior nu-
rostrally in the reuniens and rhomboidalis components of rich substrate for interaction among the various fields of
the massa intermedia. Rostro-lateral components peel off the nonspecific system and with adjacent specific and as-
in arcs, flowing through or around more lateral nuclear sociational nuclei. As suggested by Figure 17, the ascend-
masses to reach putamen and caudate. ing axonal system from the posterior two-thirds of the
Although it has generally been agreed that no axons of brain stem runs roughly parallel to the thalamic nonspe-
the posterior half of the thalamic nonspecific system reach cific system and provides one of its most important sources
cortex, more sensitive tracking methods in the hands of of afferent excitation.
some investigators1136 now suggest that delicate cortical This relationship is shown more clearly in F i g u r e 18,
projections may, in fact, exist. Golgi methods have not where a dense collateral mass infiltrates the intralaminar
enabled us to trace such axons to their destination, al- system from ascending brain-stem reticular fibers as well
though there seems no question about cortical termina- as from the adjacent, much attenuated spino-thalamic
tions for more rostrally situated elements. The Golgi tract. Individual elements of this influx penetrate not only
methods do, however, show the intensive collateralization the entire ipsilateral intralaminar system, but reach some
of these caudal and rostral components, which provide a of the contralateral fields—at least in the rodent (specifical-
FIGURE 18 Mass of collateral and terminal fibers from as- erally via the reuniens nucleus (Re). Other abbreviations in-
cending reticular components (AR) and spino-thalamic clude Aq, aqueduct of Sylvius ; Pv, periventricular fibers;
tract (Sp) terminate in the posterior half of the intralaminar and fr, fasciculus retroflexus. Ten-day-old rat. Rapid Golgi
fields, including parafascicular (Pf); paracentral (Pc); central modification.
lateral (CL); central medial (CeM), and project contralat-
of modulatory control exerted by intralaminar nuclei shrinks in size and importance. One might wonder wheth-
upon a background of ongoing, brachium-derived excita- er this feature of rodent thalamo-cortical anatomy might
tion in VL neurons.107 not be substantially implicated in the phenomena of corti-
In the rodent, massive commissural patterns are formed cal equipotentiality described by Lashley108 in rats (Chow,
by intralaminar axons. A series of fibro-nuclear masses this volume). In a similar vein, with the progressive de-
that enable intensive bilateral communication have been crease of commissural mass to the point at which 30 per
described, including the nuclei reuniens, rhomboidalis, cent of the human thalami may be totally devoid of massa
and interantero medialis. This allows for a massive system
- intermedia bridging,'" there may reside substrate for the
of re-entrant loops of varying lengths' connecting both rise of laterality in primate and man.
sides of the thalamus, and also facilitates communication of It appears highly likely that a cortically directed projec-
nuclear fields with both cortical hemispheres. The inten- tion arises from the anterior third of thalamic nonspecific
sity of such crosscommunication decreases as the phylo- fields. In Figure 21, part of this system can be seen leaving
genetic scale is ascended and midline-bridging tissue the critical antero-medial angle of the field. Such axons
FIGURE 20 Vignette taken from a horizontal sagittal sec- (drt) and pallido-thalamic (pt) bundles respectively. Also
tion through the thalamus of a 7-day-old rat showing some visible are sectors a, b, c, and d, of VA, the nucleus reticu-
interrelations between thalamic nonspecific system fibers and laris thalami (nR) more anteriorly, and the ventrobasal com-
the ventral lateral and ventral anterior fields. Cells and fibers plex (VB) more posteriorly, receiving the terminating me-
of the thalamic nonspecific system (Thal. Retic.) dial lemniscus (lem). One centrifugal fiber (ct) is seen ending
culminating in the rostral-running projection or in VB, while the ascending reticular system (ars) sends col-
nonspecific radiation (nsr) send terminals and collaterals into laterals toward the VA field. Rapid Golgi modification. (
the neuropil fields of ventral lateral (VL) and ventral anterior ( From Scheibel and Scheibel, Note 110)
VA) nuclei, whose primary afferent sources are the
dentato-rubro-thalamic,
tegmentum (Figure 23), thereby providing a hierarchy of though there is a consensus that the distribution trans-
re entrant circuits." Such feedback loops appear to play
- cends that produced by stimulation of specific thalamic
on neurons of both specific and nonspecific thalamic sys- nuclei. Our own investigation of this projection is still in-
tems and may serve as substrate for recruitment poten- complete, but the data are suggestive. In rats and mice, the
, tials.18,19 They may also provide circuitry essential to the axonal outflow from the anterior third of the intralaminar
alternating excitatory postsynaptic potential (EPSP) and fields appears to project rostrally and ventrally via the in-
inhibitory postsynaptic potential (IPSP) swings described ferior thalamic radiation, just lateral to the mass of the
in specific thalamic cells secondary to afferent barrage." septal nuclei. The fibers can be followed forward to ap-
parent simple ascending (axodendrite?) cortical termina-
TIIALAMO-CORTICAL PROJECTION The projection of tions in orbito-frontal cortex. Each fiber may subdivide
thalamic nonspecific systems upon cortex poses a problem into many branches while still in the subgriseal white mat-
that requires further investigation. Investigators do not ter, and the most caudal branches may reach almost to the
fully agree on how recruitment potentials are distributed frontal motor fields.
over cortex following intralaminar stimulation," ,2° al- Such data appear to complement the findings of Velasco
FIGURE 22 Portion of the anterior ventral sector of the nu- passage. The entire observed course of a fiber of unknown
cleus reticularis thalami in 12-day cat as seen in sagittal sec- Drigin, d, lies within the nucleus. Two cells, e and f, of the
tion. The dense matting of the dendrite mass is seen paritcu- ventral anterior nucleus, show dendritic configuration typi-
larly along the inner border of the nucleus, nR; a, initial :al of this field. Axon g is emitted from a n. reticularis cell
intranuclear path of an axon with its primary collateral sys- whose soma remains unstained. Cell h of the n. reticularis
tem limited to the n. reticularis; al, its caudal path; a2, emits dendrite h', projects into more rostral white matter
penetrating the ventral anterior nucleus, VA; and a typical cerebral peduncle), and loses its filamentous spines as it
bushy terminal dendrite structure, a3. Fibers b and c, are does ;o. Other abbreviations include VB, ventrobasal
centrifugal and centripetal elements, respectively, pene- complex; Col. s.; superior colliculus ; Teg., Tegmentum;
trating the nucleus and emitting collaterals b' and el en Caud., caudlate. (From Scheibel and Scheibel, Note 111)
FIGURE 2 3 Slightly schematized horizontal sagittal section dal trajectory and projecting into specific and nonspecific
through the thalamus of the mouse, showing some thalamic thalamic fields. Similarly, in the case of neuron i, structures
afferent and efferent constituents on the right, and the course marked i2,3,4 represent collaterals infiltrating the thalamic
of two nucleus reticularis thalami axons on the left, ventral and lateral nuclear masses while it represents a short
elements h and i and two n. reticularis neurons. At h4 and h5 collateral projecting rostrad into the striatum (Str). All other
the axon of h collateralizes within n. reticularis, while h1,2,3 abbreviations as in previous figures. (From Scheibel and
represent collaterals generated along the length of the axon Scheibel, Note 111)
in its cau-
and secondary fields that relay raw information rostrally, by those data that are most "exotic"—or most compelling
and upon the remainder of the reticular core itself. Its vol- biologically. Like some stern, harried father figure, the
ume is small in comparison with cortex and cerebellum, core has limited patience and limited time-binding re-
and economy probably demands repeated use of its rela- sources. Its logic is wide but superficial, and its decisionary
tively limited amount of modular logic.62 apparatus does not permit the luxury of hesitation.
It seems likely that stimulus patterns continuously re-
circulate through the millions of re-entrant loops as de- Summary
cisional modes are reached. At the same time, competition
for the interest of the reticular arrays must be high, and Modern structural and operational concepts of the reticu-
neural supremacy is gained for that moment in time only lar core of the brain stem have emerged over the past 60
THE DIFFERENT EMPHASIS that has been placed at different the cerebral cortex plays a predominant role in emotion,
times upon neural activity at either the cortical or the sub- first in simply apprehending the object, then in feeling it
cortical level can be well exemplified by the history of re- emotionally. If we want to state this somewhat differently,
cent theories of emotion. Psychological thinking on this the cerebral cortex enjoys predominant attention in the
subject was dominated at the end of the last century and James-Lange theory because it refers exclusively to emo-
throughout the first three decades of the present one by tional feeling.
the so-called James-Lange theory.1,2 The neural basis for Cannon3,4 strongly objected to James's and Lange's
this theory is schematized in the drawing of Figure 1 (left), opinions and formulated the so-called thalamic theory of
taken from a paper by Cannon.3 As Cannon says, "accord- emotion. The neural basis for this theory was schematized
ing to the Jarries-Lange theory an object stimulates one or by Cannon3 himself in the drawing reproduced in Figure
more receptors (R, in Figure 1), afferent impulses pass to 1 (right), and has been conveniently summarized by
the cortex (path 1) and the object is perceived; thereupon Lindsley5 as follows: "An external emotion-provoking
currents run down to muscles and viscera (path 2) and al- stimulus excites receptors (R) and starts impulses toward
ter them in complex ways; afferent impulses course back the thalamus (path 1). . . . Thus efferent discharges are set
to the cortex (paths 3 and 4), and when there perceived up in path 2, either through direct activation of the thala-
transform the 'object-simply-apprehended' to the 'object- mus over path 1 or after impulses have passed to cortex (
emotionally-felt' ; 'the feeling of the bodily changes as path 1'), where they inactivate inhibition over path 3,
they occur is the emotion—the common sensational, asso- which allows patterned motor responses in the diencepha-
ciational and motor elements explain all,' to quote James's lon to find expression in effectors via.path 2. At the same
expression." Obviously, then, in the James-Lange theory time an upward discharge in path 4 carries to the cortex
an appreciation of the pattern just released. . . . The differ-
ence between this view and that of James and Lange is that
ALBERTO ZANCHETTI Istituto di Patologia Medica, Univer- for Cannon 'the peculiar quality of the emotion is added
sity di Milano, and Gruppo Nazionale di Medicina Sperimentale to simple sensation when the thalamic processes are
del Consiglio Nazionale delle Ricerche, Milano, Italy roused.'
NOTES 895
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