Download The projection of the lateral geniculate nucleus to area 17 of the rat

Journal qf Neurocytology 5, 63-84 (I976)
The projection of the lateral geniculate nucleus to
area I7 of the rat cerebral cortex.
I. General description
A L A N P E T E R S and M A R T I N L. F E L D M A N
Department of Anatomy, Boston University School of Medicine, Boston, Mass. 02118 U.S.A.
Received I8 July I975; revised I7 September I975; accepted 25 September I975
Summary
Lesions were made in the lateral geniculate nucleus of the rat and the consequent degeneration in area
I7 of the cerebral cortex was studied by light and electron microscopy. These lesions produced
prominent degeneration of axon terminals in layer IV extending into layer t I I and a much lesser
amount in layers I and VI. The darkened degenerating axon terminals forming asymmetric synaptic
junctions and were frequently surrounded by hypertrophied astrocytic processes. These terminals
appeared to be disposed randomly, forming no discernible patterns. In layer IV 83 % of the synapsing,
degenerating terminals formed junctions with dendritic spines, 15 % with dendritic shafts, and 2 % with
neuronal perikarya. The dendritic shafts and neuronal perikarya appeared to belong to spine-free
stellate cells. The dendrites giving rise to the spines receiving degenerating axon terminals eoutd not be
identified, for most of the spines appeared as isolated profiles that could not be traced back to their
dendritic shafts. One example of a degenerating axon terminal synapsing with an axon initial segment
was encountered. Small, degenerating myelinated axons were prevalent in layers VI, V and IV, but
were only infrequent in the supragranular layers. These results are compared with those obtained in
other studies of thalamocortical projections.
Introduction
Among the first anatomical studies of the geniculocortical visual projections in the rat was
the work by Lashley (1934, 194z) who made lesions in the cerebral cortex and then studied
the form of the retrograde degeneration in thionin stained preparations o f the lateral geniculate body. Lashley's experiments showed that the geniculocortical projections to the visual
cortex emanate from the dorsal lateral geniculate body and project to the striate, or primary
visual, area, which he defines as that portion of the occipital cortex having closely packed
granule cells in layer IV. Furthermore, Lashley (1934) was able to surmise that the projections of the lateral geniculate nucleus to the striate cortex display a point-to-point cortes9 r976 Chapman and Hall Ltd. Printed in Great Britain
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pondence. Projections of the lateral geniculate body to the occipital cortex were also shown
by Clark (I932) and Waller (I934).
Recent electrophysiological studies of the visual system of the rat have demonstrated that
the primary visual area has a distinct and precisely arranged retinotopic organization
(Montero, Rojas and Torrealba, I973). Furthermore, lesions produced by the recording
electrodes placed in the primary visual area showed that its boundary coincides with that of
the closely packed granule cells of layer IV, characteristic of area z 7 as defined by Krieg
(I946). Beyond this primary area are the peristriate areas i8 and zSa, in which there are
other retinotopic representations (Montero, Bravo and Fernandez, I973). These results both
confirm and refine those of previous electrophysiological studies of the location of the primary
visual cortex in the rat (Le Messurier, I948; Adams and Forrester, 1968).
In the past few years our knowledge of the function of the visual pathways in the cat and
monkey has increased considerably through study of the organization of the anatomical
distribution of the geniculocortical afferents within the visual cortex. Unfortunately, information about the distribution of the geniculocortical afferents within the rat visual cortex
has not received the same attention. So far as we are aware the terminations of the primary
afferents had not been examined directly until Ribak and Peters (I975) examined them by
using tritiated proline injected into the lateral geniculate body. Their autoradiographic
studies confirmed that the dorsal portion of this nucleus projects to area 17 (Krieg, 1946) and
show that the projection extends to the zones of transition between this area and the peristriate areas z 8 and 18a. As in studies of the terminations of geniculocortical afferents in other
animals (e.g., Hubel and Wiesel, I962, I972; Colonnier and Rossignol, I969; Garey and
Powell, I97z; Polley, x971 ; Benevento, I972; Rosenquist, Edwards and Palmer, 1974), it
was found that the major site of termination of the geniculocortical afferents is layer IV, with
a secondary site of termination in layer I. An elevated grain count was also observed in upper
layer VI, although the meaning of this observation was not clear.
In the present study, anterograde degeneration in the rat visual cortex was examined
following lesions placed in the lateral geniculate body. Observations were made with both
the light and electron microscopes. The point of the study was to assess the distribution of
the terminal degeneration at the electron microscope level and to attempt to identify the
cortical neuronal elements in layer IV receiving the geniculocortical afferents. In this first
article the nature and the distribution of the geniculocortical afferents will be considered,
and in subsequent articles we will give an account of the forms of some of the postsynaptic
elements as they have been derived from reconstructions based upon serial thin sections.
Methods
The data on which this study is based are derived from a series of Sprague-Dawley albino rats, three
months of age. In these animals, unilateral electrolytic lesions were placed in portions of the lateral
geniculate nucleus (LGN). Lesions were placed stereotactically, under chloral hydrate anesthesia,
using a Grass LM-4 lesion maker. The electrode approach was made through a 4 mm hole in the skull
over the contralateral hemisphere, at an anterior-posterior level corresponding to that of the LGN.
The electrode angle was 55~ from the vertical. The electrode track passed through the corpus callosum
near the midline and through the medial hippocampus on the side ipsilateral to the lesion.
Geniculo-cortical projection in rats. I
65
With regard to this approach for making lesions, it can be stated that passage of the electrode
through the corpus callosum should not be expected to affect our results. A number of studies (e.g.,
Jacobson, 197o; Jacobson and Trojanowski, 1974) have shown that area 17 of the rat is largely free of
callosal connections except, perhaps, at its lateral border where it meets area I8a (Heimer, Ebner and
Nauta, i967). Furthermore, such callosal fibres principally terminate in the supragranular layers
(e.g., Lund and Lurid, 197o), whereas, as will be shown when our results are described, lesions of the
lateral geniculate nucleus primarily produce degeneration in the granular layer IV.
Following a post-operative survival period of 2 or 4 days, the animals were anesthetized, artificially
respired, and perfused through the ascending aorta with concentrated and dilute buffered aldehyde
mixture, as previously described (Peters, 197o; Peters and Walsh, 1972). For assessment of the lesions,
a block of tissue containing the entire L G N was removed, embedded in low-viscosity nitrocellulose,
and sectioned serially at 50 ~zm. The sections were stained individually in 0.o5% toluidine blue-o and
mounted. Light microscopic examination of this material revealed lesions in the L G N (Gurdjian,
1927; Swanson, Cowan and Jones, I974) in five animals. In one of these animals the lesion was
extremely small and this case was not included in the study. The remaining four animals were processed
further for analysis of degenerating terminals in the occipital cortex.
For correlated light and electron microscopic examination of degeneration in the visual cortex, small
tissue blocks from ipsilateral area 17 (Krieg, I946) were removed. Other blocks were also taken from
the cortex of area 41 bilaterally to serve as controls. Following osmication and dehydration, the blocks
were embedded in an Epon-Araldite mixture. The plastic-embedded blocks were mounted on stubs
of wooden dowel with sealing wax and oriented for sectioning in a plane parallel to the pyramidai
apical dendrite shafts. Several 5 ~zm sections were stained by a Fink-Heimer method (Heimer, I969)
for light microscopic examination of the laminar distribution of degeneration. Thin sections from the
block face were then taken, stained with uranyl acetate and lead citrate, and examined in A.E.I. 6B and
Corinth 275 electron microscopes.
In addition, layer IV was studied in the tangential plane. To accomplish this, the depth of layer
IV was estimated from a vertically oriented section of a tissue block. The block was then removed from
the wooden dowel, turned through 9o~ and remounted. It was then trimmed down to the level of
layer IV and after 5 Iam sections had been stained by the Fink-Heimer method to show the presence
of degenerating axon terminals thin sections were taken for electron microscopy.
Results
Lesions in L G N
I n animal LIoT, the lesion was relatively small and confined to the dorsal L G N . T h e lesion
was a laminar one and situated along the posteromedial border of the nucleus. Approximately
25% of the dorsal L G N was damaged by the central region of destruction and a thin rim of
necrosis surrounded the lesion.
T h e lesion in animal L I I 6 extensively damaged both the dorsal and ventral divisions of
the L G N . T h e lesion was roughly spherical in shape, with its medial portion destroying
m u c h of the medial lemniscus and ventrobasal complex. Anteriorly, both divisions of the
L G N were damaged. T h r o u g h m i d - L G N levels the ventral division and the lower twothirds of the dorsal division were destroyed. Posteriorly, approximately 85% of the ventral
L G N and 75 ~o of the dorsal L G N were damaged.
T h e large ovoid lesion in animal L I I 7 involved both divisions of the L G N . T h e dorsomedial pole of the lesion also damaged the lateral posterior nucleus o f the thalamus. At
anterior and middle levels o f the L G N , the lesion was situated medially, and destroyed from
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20% (at anterior levels) to 5o% (at middle levels) of both dorsal and ventral divisions of the
LGN. Somewhat more posteriorly, the lesion destroyed all of the dorsal L G N and the
upper half of the ventral LGN. Posteriorly, only the lateral half of the dorsal division was
damaged.
The lesion in animal L I I 8 was generally spherical in shape, and was centered in the
anterior half of the L G N , though sparing the anterior pole. The medial portion of the lesion
damaged the medial lemniscus and ventrobasal complex. A region of involvement extended
caudally, past the posterior pole of the L G N , to partially damage the medial geniculate
nucleus. The lesion did extensive damage to the ventral L G N and much less damage to the
dorsal division. The largest amount of dorsal L G N involvement occurred at mid-LGN
levels, where approximately the ventral 25% of the dorsal division was damaged.
In view of the fact that it is only the dorsal division of the rat L G N which projects
directly to area 17 (see Lashley, I94I ; Ribak and Peters, I975), one way in which the above
lesions can be ordered is in terms of the amount of damage to the dorsal LGN. Ranked this
way, the lesions fall roughly into two groups: extensive damage to dorsal L G N in L I I 6 and
LI 17, and considerably less damage to dorsal L G N in LI o 7 and L I 18.
Light microscopic observations in area z7
Fink-Heimer preparations from the plastic-embedded visual cortex blocks were examined in
the light microscope to determine the intensity and laminar distribution of the degeneration,
and to ascertain whether there was any evidence of topographical distribution of degeneration
products.
Degeneration, as subsequently verified in the electron microscope, was evident in visual
cortex blocks from all four animals studied, though the intensity of degeneration varied. The
degeneration product consisted of larger granules with a high packing density and it appeared
against a background of fine, sparsely distributed grains similar to those seen in FinkHeimer preparations from the control blocks. In each of the four animals, the degeneration
was preferentially located in layer IV with a slight extension into layer III (Figs. I and 2).
The Fink-Heimer sections were used as a guide in trimming the individual blocks for thin
sectioning, the intention being to ensure that the ultrastructural analysis was carried out on
cortical regions containing relatively heavy degeneration.
Layer IV in the Fink-Heimer preparations was carefully examined in both vertical (Fig. I)
and tangential (Fig. 2) planes for evidence of organization of degeneration product into
discrete patterns. No evidence for preferential grouping of degeneration product into either
Fig. I. Light micrograph from a Fink-Heimer preparation of a thick plastic section of area I7. This
vertical section shows part of layer V to the left and layer IV to the right. Layer IV shows dense
particles of degeneration product and the parallel arrays of apical dendrites that form the clusters
(~ s). • 400.
Fig. z. Light micrograph from a Fink-Heimer preparation of a thick plastic section taken in the
tangential plane. The dense particles of degeneration product are dispersed randomly and show no
preferential distribution with respect to the dendritic clusters, one of which is enclosed within the
dashed circle. • 68o.
All subsequent examples of degeneration are taken from layer I V of the rat visual cortex.
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radial or laminar aggregations was found. Instead, the degeneration appeared to be scattered
randomly through layer IV.
As mentioned above, the intensity of degeneration varied somewhat among animals.
Interestingly, the density of degeneration product paralleled the amount of lesion damage
sustained by the dorsal division of the L G N . The densest cortical degeneration was seen in
the Fink-Heimer preparations of animals L I I 6 and Lrr7, the two animals in which the
dorsal L G N was extensively damaged by the lesions. Degeneration appeared less pronounced
in animals LIo7 and LIIS, in which there was considerably more sparing of the dorsal
LGN. On the other hand, the extent of damage to the ventral L G N did not correlate with
the amount of degeneration observed in the visual cortex. In animals L~ z6 and LI I8, for
example, the ventral L G N was extensively damaged, yet the observed cortical degeneration
was dense in LI I6 but notable sparser in LI I8.
Electron microscopic observations in area z 7
All of the degeneration to be described in these electron microscope observations is in area 17
of the cerebral cortex ipsilateral to the lesioned lateral geniculate body. By 2-4 days,
degenerating geniculo-cortical axon terminals show the dense mode of degeneration as
described by, among others, Colonnier (z964) , Gray and Guillery (I966), Westrum (I969,
I973), and Raisman and Matthews (x972). That is, the degenerating axonal boutons eventually become electron dense, but they do not display an increase in neurofilaments as occurs
in some other systems.
The majority of degenerating axon terminals are contained in layer IV, and this band of
degeneration extends somewhat into layer III. Even in layer IV, however, not more than a
few per cent of the axon terminals show degenerative changes, and the amount of degeneration shown in Fig. 3 is above average. In layer I the number of degenerating axon terminals
is very small, but they are readily apparent. In layer VI, on the other hand, the few degenerating axon terminals present are hard to find, since they are masked by large numbers of
degenerating myelinated axons and other unidentified dense profiles. Hence, the distribution
of degenerating axon terminals in area z7 is essentially similar to that shown by our earlier
study utilizing radioactive proline (Ribak and Peters, I975). However, the degenerative axon
terminals in layer VI are much less frequent than would have been predicted from the
radioactive isotope study.
Of the degenerating axon terminals displaying their synaptic junctions (Fig. 3, +s), in
every instance except one each junction has a clearly defined asymmetric (Colonnier, I968),
or Gray type I (Gray, z959), configuration. That is, the synaptic cleft is about 3o um wide
and the postsynaptic membrane has a prominent density, or coating, on its cytoplasmic face.
Fig. 3. A number of degenerating axon terminals (d) are present and in contrast to the other, and
normal, axon terminals (At) they are dark. Most of the degenerating terminals are adjacent to dendritic
spines (sp) and are frequently enclosed by hypertrophied astrocytic processes (As) containing glycogen
granules. Such hypertrophied astrocytic processes are more prominent than the thin, sheet-like ones
(As1) associated with normal axon terminals. Asymmetric synaptic junctions between degenerating
axon terminals and dendritic spines are indicated by (-~ s). • 22 ooc.
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The exception is a degenerating terminal which synapses with the initial segment of an axon.
No degenerating terminals forming definitive symmetric, or Gray type II, synapses have
been encountered, and no images in our preparations have led us to suspect that geniculocortical afferents form symmetric synapses. This is emphasized since as pointed out by
Westrum (I969), and by Grofovfi and Rinvik (I97O), symmetric synapses involving degenerating axon terminals can be difficult t o identify because the very slight postsynaptic
densities which characterize such synaptic junctions may be obscured.
In each of the animals examined a spectrum of degenerative changes has been encountered.
A few of the axon terminals in the experimental animals show an unusually concentrated
packing of synaptic vesicles rarely, but sometimes, encountered in preparations from control
material. Although such a packing of synaptic vesicles accompanied by a slight increase in the
density of the matrix of the cytoplasm has been described as a feature of the early stages of
degeneration (e.g., Raisman and Matthews, I972) it is not possible to be absolutely certain
that such terminals are undergoing degenerative changes.
Axon terminals which display a more intense darkening of the cytoplasmic matrix have
been encountered only rarely in control animals. Consequently, these are the ones which are
considered to be affected by the experimental lesions. Some of the obviously darkened axon
terminals show a few remaining, lucent and swollen synaptic vesicles (Fig. 4 and 9), and
rather deformed mitochondria (Fig. 3). But in the great majority of altered terminals the
organelles either cannot be clearly discerned (Figs 5, 6 and 7), or have disappeared so that
the dense matrix of the axon terminal has assumed a more or less uniform appearance (Figs
8 and Io). This increase in the density of the degenerating axon terminals is accompanied by
an increase in the irregularity of their contours.
In the normal cerebral cortex of the rat many of the synaptic unions between axon terminals and their postsynaptic elements are at least partially surrounded by sheet-like astrocytic processes (Fig. 3, As1). These neuroglial processes appear to be the ones that show
hypertrophy (Fig. 3, As) as axon terminals degenerate. Thus, the astrocytic processes become more obvious and as they hypertrophy their cytoplasm frequently comes to contain
glycogen particles (see Figs. 7 and 8) which are more prominent than in material from control
animals.
Fig. 4. This degenerating axon terminal (d) is not completely darkened, so that some synaptic vesicles
(sv) are still apparent. The terminal forms an asymmetric synaptic junction (~-) with a dendritic spine
(sp) and is surrounded by hypertrophied astrocytic processes (As). • 45 ooo.
Fig. 5. This degenerating axon terminal (d) forms asymmetric synapses (-~ s) with two dendritic spines
(sp). Both the spines and the terminal are enclosed by astrocytic processes (As). The lower spine
contains a dense inclusion. • 4o ooo.
Fig. 6. The degenerating axon terminal (d) is apparently detached from the postsynaptic dendritic
spine (sp). Only a sliver of the terminal is still attached to the synaptic junction (~). x 5oooo.
Fig. 7. The dark degenerating axon terminal (d) is forming an asymmetric synaptic junction with a
dendritic spine (sp) ai~dis enclosed within an astrocytic process (As) containing glycogen granules. At
the synaptic junction the presynaptic membrane is accentuated. A similar accentuation occurs at
another site (-~) away from the junction, and at this site the interval between the astrocytic membrane
and that of the terminal is widened. The result is a configuration resembling a synaptic junction. •
4~ooo.
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Some of the axon terminals in advanced stages of degeneration have extremely collapsed
and irregular profiles. Thus they form dense sheets that end in bulbous enlargements and
extend out from the portion of the terminal attached to the synaptic junction (Fig. 8). Other
examples show the axon terminals disintegrating into a series of dark and isolated membrane
bound profiles, enclosed by astrocytic processes. By this stage the degenerating axon terminals are essentially detached from their postsynaptic partners. Despite this separation of the
two components of the synapse, the presynaptic membrane together with a sliver of the
degenerating axon terminal cytoplasm remains attached to the synaptic junction (Fig. 6). In
many instances it has been observed that the presynaptic membrane at a synaptic junction
becomes accentuated as the axon terminal degenerates, so that this portion of the membrane
appears darker than that bounding the rest of the degenerating terminal (see Figs. 5 and 7).
Sometimes a degenerating axon terminal involved in a synaptic junction with a postsynaptic
element will show a similar accentuation of a portion of its plasma membrane at another
location, where it is facing the plasma membrane of a surrounding astrocytic process (Fig. 7,
+). At such locations it is not uncommon for the plasma membranes of the degenerating
terminal and the astrocytic process to be separated by a widened interval, similar to that
occurring at a synaptic junction. The similarity with a synaptic junction may be heightened
by the presence of a dark line bisecting the extracellular space between the two membranes
(Fig. 7). Although we cannot be sure of the interpretation of such images, it seems likely that
they represent examples of situations in which the degenerating axon terminal has become
detached from its postsynaptic element. Indeed, somewhat similar images have been seen by
Sotelo (I973) in the cerebellum of the staggerer mouse mutant. In this mutant the spines
of the Purkinje cells fail to develop and the terminals of the parallel fibres form synapse-like
junctions with the processes of glial cells. It should be mentioned, however, that we have not
recognized the postsynaptic elements of synapses from which the degenerating axon terminals
have become completely detached, although Westrum (I969, I973) has described the presence of unoccupied postsynaptic sites after 3 days postoperative survival times in the rat
olfactory bulb and after only 36 h in cat trigeminal nucleus.
To assess the character of the postsynaptic elements involved in the formation of synapses
with geniculocortical afferents in layer IV, tangential sections through this layer were
Fig. 8. T h e darkened axon terminal (d) is synapsing with a dendritic spine (sp) and is enclosed by a
complex of hypertrophied astrocytic processes (As) containing glycogen particles. Dense sheets extend
from the degenerating terminal and pass between the astrocytic processes. One of these sheets extends
into an enlarged portion of the degenerating axon terminal that synapses with a second dendritic spine
(spl).
• 30000.
Fig. 9. In the centre of the field is a dendrite (den) which synapses with three normal axon terminals
(Atl-Ata) and a degenerating one (d). This darkened terminal contains lucent vesicles and it also
synapses with a dendritic spine (sp). • 4oooo.
Fig. io. This is another example of a dendrite (den) forming an asymmetric synaptic junction with a
degenerating axon terminal (d). T h e shaft of this dendrite also receives a normal axon terminal (At).
X 40000.
Fig. I I . Two degenerating myelinated axons. One of the axons (AXl) is dark. Th e second (Ax2) is still
lucent and shares its sheath with a vacuolated profile (v) that is intimately surrounded by lamellae.
• 35ooo.
PETERS and FELDMAN
74
examined and every degenerating profile not contained within a myelin sheath was characterized. T h e results are given in Table I. It will be seen that o f the 525 profiles examined 47%
are enclosed in or immediately adjacent to hypertrophied astrocyfic processes, but show no
synapfic junction in the plane of section. T h e remaining degenerating profiles display their
postsynaptic junctions, so that in most cases the nature of the postsynaptic element can be
identified.
Some 83% of the degenerating terminals forming recognizable synapses in layer IV do so
with dendritic spines (Figs. 3-8; Table I). Since individual sections rarely show dendritic
Table I. Degenerating axon terminals of layer IV
Number
%
%of
of total
synapsing
profiles
In, or adjacent to, astrocytic processes;
No synaptic junction apparent.
Synapsing with dendritic spines
Synapsing with dendritic shafts
Synapsing with neuronal perikarya
Unidentified profiles
248
213
37
6
2I
47%
4I%
7%
i%
4%
83%
I5%
2%
Total
525
100%
100%
spines which are connected with their parent dendrites, it is not surprising that the bulbs o f
the spines synapsing with the degenerating terminals appear as isolated profiles. Most commonly the degenerating terminals are seen to synapse with only a single spine, but on occasion
the same terminal synapses with a second spine (Fig. 5). Rarely a dendritic spine receives
both a normal and degenerating axon terminal. T h e cytology of the dendritic spines does not
appear to be altered by the presence o f the degenerating terminal, although there is sometimes a dense m e m b r a n e - b o u n d inclusion in the spine cytoplasm (Fig. 5) and a swollen
cistern may be present in the cytoplasm of the dendritic shaft close to the origin of the spine.
Frequently both the bulb of the spine and the degenerating terminal are completely enclosed
within hypertrophied astrocytic processes. However, as will be shown in a later article in
which the postsynapfic spines have been traced back to their parent dendrites in serial thin
Fig. I2. Most of the field is occupied by part of a microglial cell (M) adjacent to a neuron (N). Within
the microglial cell is a degenerating axon terminal (d) forming an asymmetric junction (~) with a
rather swollen process resembling a dendritic spine (sp). The microglial cell also contains a lysosome
(L) and a membranous body (mb). • 45 ooo.
Fig. x3. Diagrammatic representation of part of a tangential section through layer IV. Neuronal
perikarya (N) are interspersed with clusters of apical dendrites (dotted circles), capillaries (C), and
neuroglial cells (G). The symbols show the positions of various degenerating elements. Some of these
are myelinated axons (~), which may form groups. The majority of degenerating axon terminals are
completely surrounded by astrocytic processes ([~), and do not display their synaptic junctions. Other
terminals synapse with dendritic spines ( 0 ) , and a few with dendritic shafts (o). For a fuller explanation see the text. Bar represents IO ~.m.
76
PETERS
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sections, this enclosure should not be taken as an indication that the spine has become
detached from its dendrite (see Colonnier, i964).
Other degenerating axon terminals form asymmetric synapses with the shafts of dendrites
(Figs. 9 and IO). The rather rounded contours of the postsynaptic dendrites when seen in
transverse sections, together with the frequent presence of other, and normal, synapsing axon
terminals leads to the conclusion that the dendrites are the smooth-surfaced ones of certain
stellate cells such as those described by Peters, (i97 I) Garey, (~97 I) Sloper, (I973a) and
Peters, Feldman and Saldanha (i976). This identification is strengthened by observations of
longitudinal sections of these dendrites, which often show some intermittent swelling of the
kind encountered in normal material when the dendrites are not optimally preserved. Sometimes one of these degenerating terminals forms a synapse with a second postsynapfic
element. This second element may either be another smooth dendrite or a dendritic spine
(Fig. 8). Such arrangements will be considered more fully when the results of the serial
section analysis are presented in the following article.
The last, and least frequent entities to form asymmetric synaptic junctions with degenerating terminals are certain neuronal perikarya in layer IV. The cytoplasmic features of these
perikarya, and the presence of other, and unaffected axon terminals forming both asymmetric
and symmetric junctions on their surfaces, indicates that these perikarya belong to stellate
cells with smooth dendrites (Peters, I97i; Sloper, I973a; Peters, Feldman and Saldanha,
i976). This conclusion is borne out by examples in which the perikarya give rise to smooth
dendrites, and by other examples in which smooth dendrites bearing degenerating axon
terminals emerge from perikarya bearing a mixture of asymmetric and symmetric synapses.
In a single instance a degenerating axon terminal was encountered that formed a synapse
with an axon initial segment. The postsynaptic axon initial segment could be identified by
the presence of the typical undercoating of the axolemma and the fascicles of microtubules
in the axoplasm (Palay, Sotelo, Peters and Orkand, 1968; Peters, Proskauer and KaisermanAbramof, I968). This seems to be an exceptional situation.
In layer I there are only a few degenerating axon terminals and on the basis of the
relatively few that have been encountered these all seem to form asymmetric synapses with
dendritic spines. The sparsity of the degeneration seen by electron microscopy in layer I
probably accounts for the apparent absence of degeneration in Fink-Heimer preparations of
thick plastic sections examined with the light microscope. The same is true of layer VI.
Here though, in addition to being sparse, the terminal degeneration is difficult to find in
electron microscope preparations, since the terminals are intermingled with large numbers of
small myelinated axons which are also degenerating (Fig. I I). Some of these axons show a
darkening of the axoplasm with little change in the myelin sheath, while others have split
myelin sheaths containing isolated whorls oflamellae. The degenerating myelinated axons are
most prevalent in the lower layers of the cerebral cortex and especially in layer VI, although
they are also common in layers V and IV. For the most part these axons pass in a vertical
direction, and although some occur singly, others are in small groups (see Fig. 13)- In the
supragranular layers degenerating myelinated axons are rare. This is to be expected from the
absence of degenerating terminals in layer II and upper layer III, and the presence of only
a few such terminals in layer I.
Geniculo-cortical projection in rats. I
77
Because of the hypertrophy of the astrocytic processes and their role in sequestering
degenerating axon terminals, the present results are in agreement with those of other
authors (e.g., Gray and Guillery, I966; Westrum, 1969; Raisman and Matthews, 1972),
who also show that astrocytes are mainly responsible for the isolation and eventual removal
of degenerating axons from the neuropil. In a few instances, however, degenerating axon
terminals attached to the bulbs of dendritic spines are enclosed within the cytoplasm of
microglial cells (Fig. 12).
To determine whether the degenerating profiles in layer IV are distributed in a pattern,
a thin section, oriented paralled to the pial surface, has been examined. A portion of this
section covering an area of approximately 24ooo ~zm2 was photographed and a montage
produced. Every degenerating profile in the area was then examined and, so far as possible,
identified. The results are shown diagramatically in Fig. 13. In Fig. 13, the various types of
degenerating profiles are shown by symbols explained in the Fig. legend. The positions of
the clusters of apical dendrites originating from the layer V pyramidal neurons (see Peters
and Walsh, 1972; Feldman and Peters, 1974) are also given, as are those of the neuronal
perikarya (N), neuroglia (G), and capillaries (C). This area has I62 degenerating profiles.
About one third of them (53) are degenerating myelinated axons, some of which are disposed
singly and others in small groups. Of 40 degenerating profiles forming synaptic junctions,
37 synapse with dendritic spines and the other three synapse with the shafts of dendrites.
Both in this section and in others examined in a more cursory fashion, the degenerating
terminals do not seem to be disposed in a discernible pattern. Neither could patterns of
degenerating terminals be seen in vertical and tangentially oriented thick plastic sections
stained by the Fink-Heimer technique (Figs. I and 2). Hence the disposition of the degenerating lateral geniculocortical axon terminals is unlike that in the cat and monkey, in which
Garey and Powell (i97i) found them to occur in groups, about IOO am apart. It is also
different from that of the degenerating thalamocortical afferents in the monkey motor
cortex, in which Sloper (I973b) found a preferential disposition of degenerating axon
terminals in the locale of apical dendrites.
We wished to determine how the distribution of degenerating axon terminals synapsing
with the various postsynaptic components compared with the distribution of all axon terminals
forming asymmetric synaptic junctions in layer IV of a normal area 17. Consequently
Table 2. Distribution of axon terminals in layer IV of normal visual cortex
Number
% of all
synapses
% of asymmetric
synapses
86%
14%
Asymmetric synapses with:
Dendritic spines
Dendritic shafts
Symmetric synapses with:
Dendritic spines
Dendritic shafts
Neuronal perikarya
372
62
74 %
I2%
5
57
4
1%
i2 %
1%
Total
500
100%
100%
78
PETERS
and
FELDMAN
a photographic montage of a thin section passing tangentially through layer IV of a
control rat was prepared. The forms of the synaptic junctions and the nature of the postsynaptic component of every synapse in an area of the montage was ascertained until 5oo
examples had been examined. The results are given in Table 2.86% of all synaptic junctions
are asymmetric, and the remaining I4% are symmetric in form. Of the asymmetric synapses
86% involve dendritic spines and i4% involve dendritic shafts. No neurons with asymmetric
synapses on their perikarya were included in the sample. As will be seen when this data is
compared with that in Table I, in layer IV the distribution of degenerating axon terminals,
in terms of the character of the postsynaptic element, is very similar to that of all axon
terminals partaking in asymmetric synapses.
Discussion
Although no definite attempt was made in this study to define the full extent of the geniculocortical projection to the cerebral cortex in the rat, the results basically agree with the
conclusions of previous authors (e.g., Lashley, I934; Adams and Forrester, I968; Montero,
Rojas and Torrealba, I973; Ribak and Peters, I975) concerning the projection from the
dorsal nucleus of the lateral geniculate body to area x7 (Krieg, I946). The primary site of
termination of these afferents is layer IV and lower layer I II of ipsilateral area 17. Although
the 5 ~m thick sections used for the light microscopic examination of degeneration as shown
by the Fink-Heimer (Heimer I969) method did not show a clear secondary termination in
layers I and VI, the presence of some degenerating terminals in these layers was apparent
with the electron microscope. In finding the primary site of thalamic terminals to be layer
IV, with a lesser input to layer I and VI, these results substantially agree with those of
workers who have examined the geniculate input to the visual cortex of the cat and monkey
(e.g., Hubel and Wiesel, I962, I972; Colonnier and Rossignol, I969; Garey and Powell,
I97I ; Polley, I97I ; Wiesel, Hubel and Lam, I974; Rosenquist, Edwards and Palmer, I974),
and the opossum (Benevento, 1972).
Despite the existence of an elevated count of grains in upper layer VI following injection
of radioactive proline into the lateral geniculate body (Ribak and Peters, I975), in the present
study only few degenerating terminals were observed in this layer. There were, however,
many thin degenerating myelinated axons in the upper portion of layer VI, and so it is
presumed that most of the labelling in this layer was attributable to these axons rather than
to the few degenerating terminals. This conclusion seems to be reinforced by the fact that
in the labelled cortex the grain count in upper layer VI is higher in the lateral than in the
medial portion of area 17 (Ribak, personal communication), which is taken to indicate that
geniculocortical afferents are passing obliquely upward through this layer in a lateral to
medial direction to attain the sites of their termination in layers IV and I. A similar labelling
of layer VI was found by Rosenquist, Edwards and Palmer (I974) in the visual cortex of the
cat after injecting radioactive amino acids into the dorsal lateral geniculate nucleus. While
they attribute the labelling to axon terminals, we are aware of no reports of degeneration of
axon terminals in layer IV in electron microscope studies of the cat visual cortex following
lesions in the thalamus.
Geniculo-cortical projection in rats. I
79
The forms of the degenerating axon terminals encountered in this study are basically the
same as those reported by other authors studying anterograde degeneration in the cerebral
cortex (e.g., Colonnier, I964; Gray and Guillery, 1966; Westrum, I969; Jones and Powell,
I97O), in that in each animal examined there is a spectrum of terminals showing various
stages of dark degeneration. One issue that requires comment, however, is the lack of
darkened profiles that could be definitely considered to be the preterminal portions of axons.
The reason for this is not apparent, for it is as though this portion of the axon disappears.
Perhaps it is withdrawn towards the axon terminal and accounts for the rather large size and
irregular shape of many of the degenerating profiles, which are frequently more voluminous
than the normal axon terminals.
Clearly, the neuroglial cells which are most affected by the degenerative process are the
astrocytes. The sheet-like processes which normally surround the synapses seem to hypertrophy and engulf the darkening axon terminals. There is little evidence that the microglial
cells are especially activated by the degenerating axon terminals, at least in the stages that
we have examined, although as shown here, microglial cells may phagocytose some axon
terminals. This absence of a marked microglial reaction is surprising in view of the observations that microglial cells engulf degenerating axon terminals in old rats (Vaughan and
Peters, 1974) and that these same neuroglial cells play a part in the removal of axon terminals
from the perikarya of chromatolysing primary motor neurons (e.g., Blinzinger and Kreutzberg, I968; Torvik, I972 ).
With the possible exception of the single terminal synapsing with an axon initial segment,
all of the degenerating thalamocortical axon terminals that we encountered formed asymmetric synapses with their postsynaptic partners. With respect to the identity of these postsynaptic elements, our quantitative analysis of their form is basically in agreement with the
analyses of others studying the thalamocortical afferents, and a comparison of various reported findings are summarized in Table 3.
Thus, as in previous electron microscope studies of thalamocortical projections, dendritic
spines are the most common postsynaptic component with which these axons synapse.
Because the profiles of the bulbs of the synapsing spines are only rarely seen to be connected
with their parent dendrites in random sections, the sources of these dendritic spines cannot be
determined from the present study. Based on the results of Globus and Scheibel (1967),
Valverde (1967) and Fifkov~i (1970) it might be expected that these spines emanate from
apical dendrites of layer V pyramids as they pass through layer IV. Globus and Scheibel
(1967) showed that after either eye enucleation or damage to the lateral geniculate body the
visual cortex of the immature rabbit has a reduced number of dendritic spines along the
proximal four-fifths of the apical dendrites of pyramidal neurons. Valverde (1967) showed a
similar diminution in number of spines along the layer V pyramidal neuron apical dendrites
as they pass through layer IV in dark-reared mice, and Fifkovfi (i 97o) obtained a comparable
result in the visual cortex of rats whose eyelids had been sutured at 14 days of age. More
recently Ryugo, Ryugo and Killackey (1975) have made the interesting observation that in
Golgi preparations of rat visual cortex the apical dendrites of pyramidal neurons lying in the
upper and lower portions of layer V react differently to bilateral enucleation. When those
portions of apical dendrites passing through layer IV were examined, Ryugo, Ryugo and
80
PETERS and FELDMAN
Table 3. Distribution of degenerating thalamocortical axon terminals on different post-synaptic
profiles
Rat, area 17
(present study)
Monkey, area I7
(Garey and Powell, I97I)
Cat, area 17
(Garey and Powell, I97i )
Cat, area 18
(Garey and Powell, I97I)
Cat, area 19
(Garey and Powell, I97I)
Cat, somatosensory cortex
(Jones and Powell, I97o)
Cat, motor cortex
(Strick and Sterling, I974)
Monkey, motor cortex, area 4
(Sloper, I973b)
Dendritic
Spines
Dendritic
Shafts
Neuronal
Perikarya
83%
I5%
2%
84%
I4%
2%
83%
I4%
3%
70%
20%
IO%
85 %
X4%
< 1%
--
25 ~
--
9I %
8%
1%
89.5%
9%
1.5%
Killackey found that only the apical dendrites of the pyramids lying in the deeper parts of
layer V lose dendritic spines. Compared to deeper lying pyramids the more superficial ones
in layer V displayed no alteration in the spine populations.
If spines of apical dendrites are one of the recipients of the geniculocortical afferents, then
it would be expected that in sections taken in a tangential plane through layer IV there would
be an aggregation of degenerating terminals around the dendritic clusters which contain the
apical dendrites of layer V pyramidal neurons (Peters and Walsh, I972; Fleischhauer, Petsche
and Wittowski, 1972; Feldman and Peters, 1974). However, no such aggregations were
encountered. Indeed, as will be shown in a later publication, which describes the results of
tracing the postsynaptic spines back to their parent dendrites in serial thin sections, the
parent dendrites of the spines seem to be only I ~m thick and so far we have been unable to
connect a spine bearing a degenerating axon terminal back to an apical dendrite. When
synapsing dendritic spines have been traced back to their parent dendrites in other studies,
the parent dendrites have also been found to be thin, with diameters of about I-I.5 ~m
(e.g., Cololmier and Rossignol, I969; Jones and Powell, 197o; Garey and Powell, 197I). The
apical dendrites do, however, seem to be one source of postsynaptic spines in the motor
cortices. Thus Strick and Sterling (I974) illustrate two postsynaptic spines that emanate
from the apical dendrite of a pyramidal neuron as it passes through layer III of the cat
motor cortex, and by studying the disposition of the degenerating thalamocortical terminals
in the monkey motor cortex, Sloper (I973b) finds them to occur most frequently in the
vicinity of apical dendrites.
As in other electron microscope studies of thalamocortical proiections, degenerating axon
terminals in the rat visual cortex also synapse with the shafts of smooth dendrites, and with
Geniculo-cortical projection in rats. I
8I
the perikarya of the neurons giving rise to these dendrites. In the rat, these stellate cell
perikarya are recognized by the fact that they form both symmetric and asymmetric synaptic
junctions with axon terminals (Peters, I97I). Only the axon terminals forming asymmetric
synapses degenerate after lesions in the lateral geniculate body. The morphology of these
stellate cells with smooth dendrites will be considered in more detail in the accompanying
article (Peters, Feldman, and Saldanha, 1976). For the present it may be stated that there is
some evidence that in the cat, human and monkey cortex these neurons are the ones whose
axons give rise to at least some of the symmetric synapses which are present on the perikarya
and proximal dendrites of pyramidal neurons (Marin-Padilla, 1969; Sloper, I973a; Jones,
1975).
Finally, it may be stated that both in the present investigation and in those dealing with
the thalamic projections to other cortices it has always been a surprise to find how few axon
terminals are induced to degenerate by thalamic lesions. It has been suggested by Jones and
Powell (197o) and by Garey and Powell (197 I) that this may be because only a few of the
thalamocorticai axon terminals display degenerative changes at any given time. However, as
pointed out by Garey and Powell (197I), even in tissue taken from animals with relatively
long survival times the percentage of degenerating terminals is not altered appreciably as
compared to animals with short survival times. Unless there is only a proportion of thalamocortical axon terminals showing recognizable degenerative changes after a specific interval,
a conclusion to be drawn is that the normal activity of the cerebral cortex in response to
visual stimuli is initiated by only a small proportion of the total number of axon terminals
present in that cortex. Additional evidence in favor of this conclusion comes from the study
of Ribak (personal communication) who has injected radioactive proline into the dorsal
lateral geniculate body of the rat. When the position of the label in layer IV of the visual
cortex is determined by electron microscopic autoradiography, he finds about the same
proportion of labelled axon terminals as is found to display degeneration after a lateral
geniculate lesion.
It is frequently assumed that there are certain elements in layer IV that preferentially
receive thalamocortical afferents. Another possibility is that every component in layer IV
capable of forming an asymmetric synapse is a potential recipient for a thalamocortical axon
terminal. This hypothesis would seem to be supported by the observation that, at least in
the rat visual cortex, the distribution of degenerating thalamocortical axon terminals (Table
I) is similar to that of all asymmetric synapses (Table 2). Hence, although thalamocortical
afferents terminate principally in layer IV, their distribution with respect to postsynaptic
targets may be essentially random, in the sense that no specific types of neurons receive the
efferents. Instead all elements in layer IV that are capable of forming asymmetric synapses
may be involved.
Acknowledgements
We wish to thank Julian Saldanha for his assistance during the course of this work, which
was supported by grant NS-o7oI6 from the National Institute of Neurological and Communicative Disorders and Stroke, of the United States Public Health Service.
82
PETERS
and F E L D M A N
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