THE JOURNAL OF COMPARATIVE NEUROLOGY 384:109–126 (1997)
Local Circuit Neurons of Macaque
Monkey Striate Cortex:
IV. Neurons of Laminae 1–3A
JENNIFER S. LUND* AND CHARLES Q. WU
Department of Visual Science, Institute of Ophthalmology, University College London,
London EC1V 9EL, United Kingdom
ABSTRACT
We continue our Golgi studies (Lund [1987] J. Comp. Neurol. 257:60–92; Lund et al.
[1988] J. Comp. Neurol. 276:1–29; Lund and Yoshioka [1991] J. Comp. Neurol. 331:234–258) of
the organization of local circuit, largely g-aminobutyric acid (GABA)-containing neurons in
macaque monkey visual cortex, area V1, with this account of the local circuit neurons lying in
layers 1 and 2/3A. These layers receive intrinsic interlaminar excitatory and inhibitory relays
from layers 3B, 4A, 4B, and 5. We describe seven varieties of local circuit neurons with somata
within layers 1-2/3A, and we compare the lateral scale of spread of the axons and dendrites of
these neurons with the size of the columnar connectional patch domains made by the laterally
spreading axon collaterals of pyramidal neurons within the superficial layers (Lund et al.
[1993] Cerebral Cortex 3:148–162). We conclude from this comparison that all of the neurons
have dendritic fields that are limited to single patch domains. Furthermore, only two of the
seven local circuit neuron varieties have sufficient axon spread to influence territory beyond
single domains, reaching into neighboring territory likely to differ in function from that
occupied by their dendrites. We have identified descending projections from particular
varieties to layers 3B, 4A, 4B, and 5 and to the white matter. We discuss the contributions that
these interneurons may make to function within the superficial cortical layers, and we
summarize our overall conclusions, so far, from our set of studies on interneurons within area
V1 of the macaque. J. Comp. Neurol. 384:109–126, 1997. r 1997 Wiley-Liss, Inc.
Indexing terms: vision; inhibition; interneuron; visual cortex; primate
This study represents a further step in our investigation
(Lund, 1987; Lund et al., 1988; Lund and Yoshioka, 1991)
of the morphology of local circuit neurons in the macaque
monkey primary visual cortex (area V1 or striate cortex) as
seen in Golgi-rapid impregnations (Lund, 1973). In our
previous studies of layers 3B–6, we have documented the
presence in each layer of several different forms of these
neurons, which generally contain g-aminobutyric acid
(GABA) and are presumed to be inhibitory (Ribak, 1978;
Houser et al., 1984). We have shown that their axons make
a local or laterally extended intralaminar arbor and, in
many cases, also make very specific interlaminar projections. Some of these local circuit neuron projections follow
the patterns of projections made by different populations
of pyramidal and spiny stellate neurons. The local circuit
neurons also provide feedback pathways and links between different channels of information flow. We have
pointed out that the lateral spread of the axons of the
interneurons, and, thus, their spatial relationships to the
topography of function across the cortex, may be an
important element in determining their different roles.
r 1997 WILEY-LISS, INC.
Below, we briefly review anatomical features of layers
1–3A that are either shared or unique to particular
divisions; it is clear that this territory is divided both
vertically and laterally into a number of different compartments, and this will bear on our later discussion of possible
functional roles of the interneuron populations described.
The laminar numbering scheme we have used for V1
cortex is shown in Figure 1. Layer 1 is sparse in cells (at
least 80% of which are GABAergic; Fitzpatrick et al., 1987)
and contains almost no somata or basal dendrites of
pyramidal neurons, although it does contain a rich plexus
of apical dendritic processes of pyramidal cells with so-
Grant sponsor: National Eye Institute; Grant number: EY10021; Grant
sponsor: Medical Research Council; Grant numbers: G9203679N, G9408137.
*Correspondence to: Professor Jennifer S. Lund, Department of Visual
Science, Institute of Ophthalmology, University College London, 11-43
Bath Street, London EC1V 9EL, United Kingdom. E-mail: j.lund@ucl.ac.uk
Received 22 October 1996; Revised 16 January 1997; Accepted 28
February 1997
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J.S. LUND AND C.Q. WU
Fig. 1. Cresyl violet-stained (A) and cytochrome oxidase (CO)reacted (B) 40 µm sections from parafoveal macaque monkey V1
cortex to illustrate the laminar numbering scheme used in this study.
The border between layers 3A and 3B is placed halfway between the
upper border of 4B and the lower border of layer 1. The border between
layers 3A and 2 is placed halfway between the base of layer 1 and the
top of layer 3B. In B, arrows indicate the positions of two CO-rich blob
regions. Scale bar 5 200 µm.
mata in underlying layers down to layer 5B (see Fig. 10B).
There are direct extrinsic afferents to layer 1 from the
intercalated layers of the lateral geniculate nucleus (LGN;
Fitzpatrick et al., 1983; Lachica and Casagrande, 1992)
and from nonspecific thalamic nuclei and other subcortical
regions (see Tigges and Tigges, 1985; Herkenham, 1986).
Layer 1 shares input from the pulvinar with layers 2 and
3A (Ogren and Hendrickson, 1977; Rezak and Benevento,
1979). Feedback pathways from extrastriate cortex also
enters layers 1 and 2 (Rockland and Virga, 1989; Rockland
and Van Hoesen, 1994; Rockland et al., 1994).
Layers 2 and 3A are rich in somata and basal and apical
dendritic processes of pyramidal neurons (about 80%
pyramids, 20% GABAergic interneurons; Fitzpatrick et
al., 1987); the region does not appear to receive much in
the way of thalamic afferents; projections of the LGN
intercalated layers to the blobs [cytochrome-oxidase (CO)rich regions] concentrate their terminal fields deeper in
layer 3B (Fitzpatrick et al., 1983; Lachica and Casagrande,
1992). Importantly, layers 2/3A are not innervated directly
by relays of excitatory spiny stellate neurons from layer
4C, which distinguishes the region from underlying layer
3B—a major recipient of these relays (Blasdel et al., 1985;
Fitzpatrick et al., 1985; Yoshioka et al., 1994). Dendritic
processes of layer 3B pyramidal neurons, driven by these
direct thalamic inputs, rise up into overlying layers 2/3A
and 1 and express a rich CO content, so that the blob zone
extends up into layer 1; many other dendritic and axonal
processes from both interneurons and pyramidal cells of
all layers except 4C enter the neuropil of the 2/3A region
(summarized in Fig. 10B).
In this study, although it was clear that layer 1 differed
in its interneuron constituents from layers 2 and 3A, no
sharp difference in interneuron varieties were found between layers 2 and 3A. There are a number of differences
between the two regions; the cell packing density in layer 2
can appear greater than in layer 3A in tissue stained for
cytoarchitecture; layer 3A, rather than layer 2, is a princi-
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
pal source of efferent projections to area V2 (Rockland and
Pandya, 1979), and layer 3A does not share feedback
terminations from visual cortical areas V2, V4, and TEO
with layers 1 and 2 (Rockland and Van Hoesen, 1994;
Rockland et al., 1994).
Despite their differences, layers 1-2/3A share input from
laterally spreading, rising relays from layer 3B pyramids
together with input from pyramids in layer 5. These inputs
are reinforced by laterally spreading collaterals from the
axons of the pyramids of the 2/3A layer itself; these
pyramidal neuron connections form a laterally running,
lattice-like continuum of patchy terminal fields in the
superficial layers, which largely (70% match) link regions
of common function (Rockland and Lund, 1983; Malach et
al., 1993; Yoshioka et al., 1996). This connectional continuum runs without apparent interruption across the
borders of at least two fixed-place blob and interblob
compartments; in these compartments lie segregated populations of efferent neurons; pyramids in the blob regions
relay to thin, CO-rich stripe compartments, and pyramids
in the interblob regions project to CO-poor stripe compartments of V2 (Livingstone and Hubel, 1984). There is no
clear evidence that blobs and interblobs have different
interneuron populations, although the level of neurotransmitter in axon terminals and other features of the neuron
biochemistry may differ between these regions, most probably due to different activity levels in the thalamic-driven
blob zones compared with interblob territory (see, e.g.,
Fitzpatrick et al., 1987).
The current Golgi study provides a morphological description of the varieties of interneurons encountered in
our Golgi impregnations together with measurements of
the lateral spread of their axonal and dendritic arbors as
well as any interlaminar projections observed. Possible
relationships of the inhibitory neurons to lattice functions
and intrinsic feed-forward inhibition are discussed, and
comparison is made with interneurons of other cortical
areas and different species. A preliminary report of this
study has appeared earlier (Lund and Wu, 1993).
MATERIALS AND METHODS
The reader is referred to our earlier papers (Lund, 1973;
Lund, 1987; Lund et al., 1988; Lund and Yoshioka, 1991)
for details of the Golgi method and our general approach to
tissue analysis. An illustration of our laminar numbering
system for area V1 is given in Figure 1; layers 2/3A occupy
the upper half of the cortical depth between the top of layer
4B and the base of layer 1 (these boundaries are usually
recognizable in the Golgi-rapid impregnations), the lower
half comprising layers 3B and 4A; layer 2 and layer 3A
each occupy half of this upper territory. Tissue from the
same series of infant and adult macaque monkeys (M.
rhesus and M. nemestrina) has been used in the current
study, as it was in our earlier studies, and an extensive
search was made by light microscopy through many sections (cut at 90 µm thickness) of a wide age range of
animals for repeated examples of morphologically distinct
cell types.
Partial drawings were made of nearly every interneuron
encountered until it was clear that examples of neurons of
similar morphology were regularly encountered; then,
detailed drawings were prepared of the most complete
impregnations of five to ten individual cells of that variety.
These drawings then served as the template against which
111
other cells were compared to see whether they resembled
or differed from that variety. If cells appeared to differ in
morphology from these template drawings of distinct
varieties, perhaps appearing as intermediate forms between two varieties or a new variety, then detailed drawings were made of these individual cells for comparison
with the sets of neurons already placed in distinct categories. In this way, we placed each neuron encountered into a
particular category. Very occasionally, we failed to make
any matches to a single cell encountered (the wide-arbor
cell described in the following section falls into that
category); however, examples of most varieties were regularly encountered, with at least two or three examples in
each of the seven to ten blocks sectioned from each
hemisphere, despite interanimal variation in frequency of
impregnation of particular varieties.
In some cases, our categories were clearly those of other
workers on cortical anatomy (e.g., chandelier, basket, and
neurogliaform cells). In some cases, we could not make a
clear distinction between two varieties described by others
(double-bouquet and bipolar), and we placed these neurons
in a single class. In other cases, our varieties had not been
described previously by others in a manner that clearly
matched our sample; in these cases, however, we were able
to match the variety quite well to similar forms in macaque prefrontal cortex in our own studies (columnar,
medium-arbor, and simple beaded varieties; Lund and
Lewis, 1993). We believe that each of our varieties is
distinctly different in morphology from the others, without
intermediate forms. However, this does not preclude the
existence of additional forms that we have failed to impregnate or the existence of differences in single varieties other
than those revealed in Golgi impregnations.
It should be noted that Golgi impregnations are very
much more successful in juvenile animals than in adults
(where myelination of the axons makes impregnation
difficult), and our illustration of cell types are from young
animals in which both axon and dendrites of single cells
are impregnated; however, the same cells are present in
the Golgi preparations from adults, with only minor
differences in axon and dendritic form but less complete in
impregnation of the entire cell. In young animals, the
dendrites of the local circuit neurons may bear many
small, thorn-like protrusions or spines, and this feature
will be noticeable in the illustrations of local circuit
neurons from juvenile animals illustrated in this study; in
the adult, the dendrites become smooth or only sparsely
spined, with some variation between individual cells of
even single varieties within single animals in the degree to
which these dendritic appendages are shed.
Dimensions of cells, as measured in the Golgi-rapid
preparations, were compared with dimensions of connectional patterns seen in V1 frozen tissue sections reacted for
biocytin, as reported in other studies (Lund et al., 1993;
Yoshioka et al., 1996). These preparations have very
similar shrinkage factors; the tissue for both is taken from
brains perfused with the same 4% paraformaldehyde in
phosphate buffer, and the Golgi-rapid osmium stage prevents further shrinkage.
RESULTS
In our search for interneurons, we examined all areas of
V1, from the foveal representation to the far periphery. We
could find no evidence for particular varieties of interneu-
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Fig. 2. A: Layer 1 neuron, variety 1:1. Axon arbor is on the right,
dendritic field is on the left. B: Chandelier neuron, variety 2/3A:1.
Axon arbor is on the right, dendritic arbor is on the left. Camera lucida
drawing of Golgi-rapid impregnations from a 5-week-old M. nemestrina. For both A and B, the axon is drawn separately from the
dendritic field for clarity. Large arrowheads indicate offset axons. Both
cells are from the outer operculum of area V1. In this and subsequent
figures, the laminar boundaries are indicated by small arrowheads,
and numbers indicate each laminar identity. Scale bar 5 50 µm.
rons being restricted to peripheral or central visual field
representations, with the one reservation that only one
example was found of the wide-arbor basket neuron variety
(see below) in layer 2-3 (in the parafoveal cortex). Examples of
the other varieties were found at all eccentricities.
they were not impregnated in the tissue from postnatal
ages examined in this study. A single morphological type of
interneuron is regularly impregnated with somata in layer
1 of our infants and more mature tissue.
Layer 1 neurons
Layer 1 of at least the juvenile monkey may contain
Cajal-Retzius neurons (Marin-Padilla, 1984). Although
these neurons are impregnated in our prenatal material,
Layer 1: Variety 1
This neuron (Fig. 2A) has a dendritic field spread of
250–300 µm, some portion of which may spread into layer
2. Its axon rapidly divides on emerging from the soma to
form a dense field of highly convoluted, beaded (presumed
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
113
Fig. 3. A,B: Columnar cells, variety 2/3A:2. The axon field is drawn separately (in each case, to the left
of the dendritic field) from the dendritic field for each neuron for clarity. Golgi-rapid impregnations from a
5-week-old M. nemestrina. Both cells are from the outer operculum of area V1. Scale bar 5 50 µm.
to be sites of synapses) processes within layer 1, with a
spread of approximately 300–350 µm. Occasionally, the
soma may lie in layer 2, but the axon rises to establish the
bulk of its arbor in overlying layer 1.
Layer 2/3A neurons
The first two cell types we describe, the chandelier
neuron and the columnar cell, are also found with somata
in the deeper regions of the superficial cortex, layers 4B,
4A, and 3B, and their axons and dendrites flow vertically
across all laminar boundaries between the base of 4B and
the base of layer 1. We have also observed chandelier
neurons in upper layer 4C-a and in layer 5 (Lund, 1987;
Lund et al., 1988).
2/3A variety 1: Chandelier cells. Whereas the dendrites of the more superficially placed neurons may cross
into layer 1, their axons do not enter layer 1; this limitation of the axon arbor distribution is consistent with the
distribution of their synaptic targets, the initial axon
segments of pyramidal cells (Somogyi, 1977), which do not
occur in layer 1. The axon field is generally centered
around the dendritic field and spreads laterally no more
than 300 µm: generally, 150–250 µm wide. The characteristic vertically arrayed, synaptic cartridges occur evenly
distributed across the axon field. The dendritic field is
more tightly focused than the axon arbor, with the dendrites forming a narrow columnar field under 100 µm wide
(Somogyi, 1977; Peters, 1984b; see Fig. 2B).
2/3A variety 2: Columnar cells. The cell bodies of
these neurons (around 17 µm in diameter) are generally
within layer 3A, i.e., the lower half of the 2/3A zone, and
only rarely as high as layer 2 (Lund and Yoshioka, 1991;
see Fig. 3). The dendrites form a narrow columnar field,
averaging about 80 µm in diameter. Roughly equal numbers of dendrites extend into territory above and below the
soma, and the more superficial segments may enter layer
1. The axon emerges as a stout trunk on the pial side of the
soma and rises to the base of layer 1 without entering it.
The axon gives off laterally running beaded collaterals
along its length, and the terminal field forms a column
around 250–350 µm wide; the dilations, which are assumed to be sites of synaptic contact, are distributed fairly
evenly, if sparsely, within the axon arbor. One or two stout
trunks also descend from the initial axon trunk, and
collateral branches can be given off in layers 3B, 4A, and
4B, whereas the trunks continue downward at least as far
as layer 5B. The main bulk of the axon collaterals are
found on a level with and to the pial side of the soma
position.
2/3A variety 3: Wide-arbor basket cells. Although
many examples have been found of the other varieties of
cells described in this Golgi study, only one example of this
cell type in layer 2/3A has been found (Jones and Hendry,
1984; see Fig. 4). Because its lateral axonal spread is the
largest of any Macaque monkey Golgi-impregnated interneuron we have found so far in area V1, we include its
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J.S. LUND AND C.Q. WU
Fig. 4. Wide-arbor basket neuron, variety 2/3A:3. The axon is drawn separately to the right of the
dendritic field for clarity. This neuron was the only one of its type that we encountered in our Golgi-rapid
impregnations of layer 2/3A. From a 3-week-old M. nemestrina in the outer operculum of V1. Scale bar 5
100 µm.
description here, because, if it is a consistent part of the
neuropil, then it may exert great impact on the range of
direct, laterally spreading inhibition in the superficial
cortex.
The soma (25 µm in diameter) lies at the 2/3A border.
The bulk of the dendrites of this cell form a columnar arbor
largely within a zone 100 µm wide above the soma in
layers 1-2/3A. The axon emerges basally and descends at
least as far as layer 5B. Beaded collaterals are given off
this trunk around the dendritic field to establish a local
dense arbor about 400 µm wide centered around the soma;
in addition, a few stout, lateral trunks travel more distantly to about 580 µm from the soma in layer 2/3, giving
off short, lateral, beaded terminal branches. The long
lateral trunks distribute as separated ‘‘arms,’’ giving unevenness in terminal distribution around the cell; one of
these trunks was traced into layer 1, where it traveled at
least 1.5 mm from the soma, emitting sparse, lateral
branches to layer 2. There was no clear evidence of
patching in the distribution of its axon terminals.
2/3A variety 4: Neurogliaform or spider-web cells.
These cells (Jones, 1984; see Fig. 5) are found occasionally
in superficial layers 2/3A in our impregnations. They are
identified particularly by their numerous but short dendrites (dendritic field approximately 150 µm wide) and
their fine, locally distributed, densely branched axon field
(about 200 µm wide).
2/3A variety 5: Cells with simple beaded axons. The
vertically oriented dendrites form an arbor within layers
1–3A about 100 µm wide or less (Fig. 6). The axon
generally emerges apically and forms an interweaving
cascade of slender, beaded processes adjacent to and
somewhat wider (200–250 µm) than the dendritic field but
with little intrusion on layer 1. Stout axon trunks begin a
descent to deeper layers, but their impregnation ceases in
our material within layer 3B (perhaps because of myelination), and, so far, the destination of these descending
trunks not been traceable in our material.
2/3A variety 6: Medium-arbor neurons. This cell type
has not been found in layers 3B-4B but is a regularly
occurring component of layer 2/3A (Fig. 7). The soma
generally lies in layer 3A; the dendrites (see Fig. 7A,
dendrites drawn together with the axon) are largely
vertically oriented, with a total arbor width 125–150 µm,
and are distributed within layers 3A-2 with little intrusion
into layer 1. The robust axon emerges basally from the
soma and rapidly divides into recurrent, spreading
branches of linear, beaded terminal processes with a total
spread of 500–700 µm; the axon resembles that of basket
neurons but does not form pericellular basket arrays. The
whole arbor has an inverted cone shape that is widest near
the top of layer 2, with almost no intrusion into layer 1,
within which terminals appear evenly distributed.
2/3A variety 7: Cells with narrowly focused, vertically oriented axon fields (double-bouquet or bipolar
cells). The somata can lie at any level in layers 2/3A
(Somogyi and Cowey, 1984; Peters, 1984a; Figs. 8, 9). The
dendrites of these neurons are mainly vertically oriented
with occasional laterally spreading branches, and the
main dendritic field is around 100 µm wide. The dendrites
of our impregnated cells are only occasionally truly bipolar
in origin (i.e., arising from two dendritic trunks, arising
from apical and basal sides of the soma; see Fig. 9A); more
usually, the cells are multipolar. The dendrites can show
slight intrusion into layer 1, but the bulk of the dendritic
field lies in layers 2/3A. The axon emerges from any point
on the soma and ascends or descends, quickly dividing into
multiple, vertically oriented, fine collaterals that together
form a narrow column. On the pial side of the soma, the
axon trunks gives off multiple collaterals to form a closeknit column of interweaving, beaded processes, often with
long side spines, that spreads through layers 2 and 1 (see
Fig. 8). In layers 3A-3B, the arbor is largely restricted to a
column of fine, vertical processes with prominent, spinelike side processes. The axon arbor width in layer 1
reaches up to 200 µm; in layer 2, occasional processes can
reach up to 300 µm laterally, but the majority of processes
are focused within a diameter of 100 µm; in deeper regions,
the column of fine axon processes is generally less than 50
µm wide. In our impregnations, the descending axon
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
115
most superficial region, layers 1–3A, of the macaque visual
cortex; Figure 10A summarizes these findings, and Figure
10B summarizes other axonal and dendritic contributions
that are made to layers 1–3A from neurons in other layers
of V1.
Relationship of interneurons to superficial
layer pyramidal neuron connectional
patch system
Fig. 5. Neurogliaform (spider-web) neuron, variety 2/3A:4, from
layer 2 of the calcarine floor region of V1 in a 5-week-old M.
nemestrina; Golgi-rapid impregnation. The axon is drawn separately
below the dendritic field for clarity. Scale bar 5 50 µm.
arbors of single cells have reduced to no more than a single
process passing below layer 4A, which then descends as far
as layer 5 and occasionally to the white matter. Others (see
Somogyi and Cowey, 1984) have reported a skein of fine
axon collaterals from single cells forming a narrow column
reaching to layer 5.
We have been unable to make a clear distinction between bipolar and double-bouquet cells on the basis of
different axon morphology; there is some variability in the
morphology of the axons of these cells in our impregnations; the majority appear to have prominent side spine
morphology, as described above, but others are finer and
less decorated with appendages (see the cells in Fig. 9). It
is therefore probable that this variety contains subclasses.
DISCUSSION
We have provided above a brief description of the
interneurons observed in our Golgi preparations of the
In the absence of any clear indication from other published studies that different classes of interneurons occupy
the blob or interblob positions or are restricted to particular parts of the visual field representation in area V1, we
will assume that all classes of interneurons that we have
described are spread relatively evenly across the lateral
extent of cortex. The absolute density of particular varieties is likely to vary on the basis of findings from immunocytochemical labeling of calcium-binding proteins and other
biochemical labels for interneurons populations (DeFelipe,
1993); but, where electron microscopic (EM) studies have
examined the issue (see, e.g., Somogyi et al., 1982; Kisvarday et al., 1993), there is overlap between axons of
individual cells of the same variety on single target
neurons. The degree of overlap in both vertical (pia to
white matter) and lateral dimensions of the cortical sheet
may well differ between varieties, given their different
dimensions and densities.
The scale of the laterally spreading, patchy lattice of
pyramidal neuron connections (Rockland and Lund, 1983;
Blasdel et al., 1985; Lund et al., 1993; Yoshioka et al., 1994,
1996; see Fig. 11A) in relation to the axon and dendritic
arbor sizes of the local circuit neurons is of particular
relevance with regard to how the superficial layer neuropil
may function. Considering the fact that the patch system
is a continuum and that each patch is only definable in
terms of its connections to particular (perhaps unique)
offset points of similar size, match in scale between the
spread of a local circuit neuron’s axon and the pyramidal
neuron connectional patch size will mean that any single
interneuron of that variety will occupy the center of a
patch, exerting a direct effect through the entire width of
the single patch, i.e., over an area likely to be territory of
similar function. If the axon is wider than the connectional
patch size, then the interneuron activity will additionally
affect neurons in territory of function unlike that surrounding the cell’s own dendritic field, even when the cell lies
centered in the patch (Malach et al., 1993; Yoshioka et al.,
1996; see Fig. 12, top). In addition, if the interneuron axon
arbor is narrower than the pyramidal neuron connectional
patch, then the cell can exert a narrowly focused effect
even within a patch boundary. The influence of interneurons with somata offset to different degrees from the patch
center on activity within the patch will gradually wane
with distance of their offset with a geometry dependent
upon the lateral diameter of their axon.
The pyramidal neuron patchy connections build in depth
to form connectional columns (about 250–300 µm diameter) that reach from the base of 4B to the top of layer 1
(Rockland and Lund, 1983). The relationship of these
anatomical connectional columns to the ocular dominance
‘‘columns’’ (actually slabs) and orientation columns defined
functionally in layers 4B-1 by Hubel and Wiesel (1972,
1977; anatomical ocular dominance columns are only seen
in layer 4C) has recently been explored by optical imaging
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J.S. LUND AND C.Q. WU
Fig. 6. Neuron with simple beaded axon arbor (axon to the left, dendritic field to the right); variety
2/3A:5, from area V1 in the floor of the calcarine fissure in a Golgi-rapid impregnation of an 8-week-old M.
nemestrina. Scale bar 5 50 µm.
(Malach et al., 1993; Yoshioka et al., 1996); there is no
simple link between these superficial layer anatomical
connections and functionally defined columns. All of the
local circuit neurons we have described within layers
1–3A, as well as those in layers 3B-4B, have dendritic
fields no wider than that of a single pyramidal neuron
connectional column. Single pyramidal neuron dendritic
fields and thalamic input ‘‘blobs’’ are also about 250 µm
wide (Fig. 10B shows the size of the blob width, with the
other neurons of Fig. 10 drawn to scale). Most of the
interneurons described have an axon arbor that matches
or is narrower than that of the dimensions of single
connectional columns (i.e., exert their maximum effect
within a column of cells with reasonably similar function).
Only two varieties, the wide- and medium-arbor cells
(varieties 2/3A.3 and 2/3A.6), have axon spreads that
would enable them to influence laterally offset territory
immediately surrounding but outside their local connectional patch, i.e., territory with functions unlike the region
occupied by their dendritic field.
Modulation beyond the patch diameter. Both of the
neuron varieties with wider axon arbors (varieties 2/3A.2
and 2/3A.6) have no axon terminals within layer 1, suggesting that they are unlikely to terminate on pyramidal
neuron apical dendrites; although their axons do not form
pericellular terminal arrays, their general resemblance to
basket neurons (whose axons are known to contact the
proximal segments of pyramidal neuron dendrites and
their somata; Kisvarday, 1992) suggests that they may
have similar contact sites on pyramidal neurons of layers 2
and 3A. If the wide-arbor interneuron 2/3A:3 is a constant
part of the superficial layer neuropil (despite our failure to
impregnate it regularly in our Golgi preparations), it could
represent a counterpart of the deeper wide-arbor basket
neurons of layers 3B-4B (varieties 4B, 4A, and 3B:3 of
Lund and Yoshioka, 1991). Our one example has an axon
spread in layer 2/3A with significant amounts of terminals
over an area of about 780 µm in diameter, i.e., much the
same spread as the axons of deeper basket cells in layers
4B-3B. We proposed in a previous study (Lund et al., 1993)
that these wide arbors might help reinforce the discontinuous pattern of connectivity of the pyramidal neurons in the
superficial layers by inhibiting pyramidal neurons in a
territory that surrounds any active point across the cortical sheet. It is, however, more likely that the single,
wide-arbor neuron we have found in layer 2/3 represents
an odd outlier in a system that predominantly occupies
layers 4B-3B (Lund and Yoshioka, 1991). Much more
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
Fig. 7. A: Medium-arbor neuron, variety 2/3A:6. Note that axon
and dendrites are drawn superimposed in their in vivo relationship.
B: Axon of medium arbor neuron, variety 2/3A:6 (soma and dendritic
117
field not impregnated; open arrow indicates axon initial segment).
Both A and B are from Golgi-rapid impregnations of the outer
operculum of V1 in a 5-week-old M. nemestrina. Scale bar 5 50 µm.
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J.S. LUND AND C.Q. WU
Fig. 8. Two double-bouquet neurons, variety 2/3A:7, from the outer operculum of V1 (A; axon to left,
dendrites to right) and from V1 in the roof of the calcarine fissure (B; axon to right, dendrites to left). Both
A and B are from 5-week-old M. nemestrina, Golgi-rapid impregnations. Scale bar 5 50 µm.
regularly encountered are the medium-arbor cells with
axon arbors widening as they rise from layer 3A to layer 2,
with no entry into layer 1. The dimensions of their axon
spread (500–700 µm) also could provide inhibition in a
surrounding territory to the pyramidal connectional patch
system (see diagram in Fig. 12, bottom).
Although the wide-arbor axons include terminals in the
home territory of the basket neuron dendritic field, we
suggest that their inhibitory impact on pyramidal neurons
is always balanced against excitatory feed-forward input
from lower layers. If the basket neuron and local pyramids
are receiving heavy direct excitation, then we suggest that
the local basket neuron contacts have little effect; the inhibitory effect of the basket neuron is hypothesized to grow as
the synapses lie farther and farther away from the center
of the activated patch, where the stimulus and its resultant excitation becomes less and less effective. The balance
between weight of excitation and inhibition is suggested to
be the key element in the activity patterns of the superficial layers, and the shift toward net inhibition should lie at
about 125 µm from the center of an activated patch.
The question remains: Why, if these medium- and
wide-arbor cells fulfill a similar function of surround
inhibition, is there not a single form of neuron providing it?
The answer may lie in the source of afferents to the
medium- and wide-arbor neurons; if each is driven by the
same sources of rising interlaminar afferents as the local
pyramids, then the deep, wide-arbor layer 4B-3B neurons
should receive input from afferents rising from layer 4C
and, perhaps, from thalamic afferents to blobs; the more
superficial medium-arbor cells should receive input from
rising projections from layer 3B, 4A, and 4B pyramidal
neurons. This stratification of afferents and wide- and
medium-arbor cells should enable the interneurons to
have the same temporal relationships to afferents at
different depths as the local pyramids.
It is known from work in cat (Kisvarday et al., 1993) that
basket neurons with a morphology similar to that of the
layer 3B-4B cells in monkey also contact each other. As one
patch system becomes active, the wide- and medium-arbor
cells within the active patches may not only inhibit
pyramidal neuron activity in surround territory, they may
also prevent inhibition of their own patch areas by inhibiting the surrounding neurons of like kind (see Fig. 12,
bottom). There is a difference in anatomical detail of the
axon arbors of the medium- and wide-arbor cells that may
suggest a slight difference in target. The 2/3A.3 wide-arbor
neuron variety, like the layer 4B-3B basket cells, has short,
terminal-side branches that closely resemble similar processes on the basket neurons of cat. These processes have
been shown by EM to terminate on pyramidal neuron
proximal dendritic segments and somata (Kisvarday et al.,
1993). The axons of medium-arbor cells have longer linear
beaded processes that have a very similar trajectory to
pyramidal neuron dendrites. It is possible, therefore, that
the medium-arbor cell axons contact dendritic branches of
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
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Fig. 9. A,B: Two double-bouquet neurons, variety 2/3A:7. Both A
and B are from the outer operculum of area V1; the axon for each
appears to the right of the dendritic field; Golgi-rapid impregnations
from 5-week-old M. nemestrina. Note the bipolar form of cell A and
compare the axon morphology of these neurons with those shown in
Figure 7; despite some differences in morphology, we were unable to
make a clear distinction into bipolar and double-bouquet classes based
on either axonal or dendritic morphology. Scale bar 5 50 µm.
the superficial pyramids; the basal or proximal apical
branch dendrites would be the most likely targets, because
the medium-arbor cell axons do not enter layer 1.
Local modulation across a patch width. Local circuit neuron candidates exist where single neurons could
exert inhibition across a pyramidal neuron connectional
column width: the layer 1 neuron (variety 1:1), the columnar neuron (variety 2/3A:2), the chandelier neuron (variety 2/3A:1), and the simple beaded axon cell (variety
2/3A:5). Each of these neurons has axon arbors with a
lateral spread similar to that of a single connectional
patch. Whereas the axons of individual columnar neurons
extend their arbor vertically, individual layer 1, chandelier, and simple beaded axon cells restrict the vertical
extent of their axons; the chandelier and columnar neurons have a continuous distribution in depth, with narrowly focused columnar dendritic fields and axon arbors
that cross all boundaries in depth of layers 4B-2.
Chandelier cells are also found in layers 4C-a, 5A, and
5B (Lund, 1987; Lund et al., 1988). Their axons are known
to provide GABAergic synapses to pyramid initial axon
segments (Somogyi, 1977). The origins of their excitatory
and inhibitory inputs are unknown. Clearly, these cells
could form a crucial gate to the pyramidal neuron (as well
as some populations of spiny stellate neuron) outputs.
Douglas and Martin (1990) have suggested on the basis of
theoretical modeling that the chandelier neurons may
work in synergy with basket neuron synapses on the
somata of the same pyramidal cells; they suggest that the
axon initial segment inhibition increases the threshold for
action potential discharge, whereas the basket neuron
synapses control the suprathreshold discharge.
Nothing is known of the interrelations between the
simple beaded cells and other cells of the 2/3A layer. The
absence of their axon collaterals in layer 1 suggests that
their target is not pyramidal neuron apical dendrites or
the distal regions of dendrites of other local circuit neurons
of the same depth, most of which intrude on layer 1; this
leaves pyramidal neuron somata or other interneuron
somata and proximal dendritic segments as possible targets. Their presence in layer 2/3A and their apparent
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J.S. LUND AND C.Q. WU
Fig. 10. A: Diagram summarizing the varieties of local circuit
neurons found in layers 1-2/3A of area V1 in our Golgi impregnations
of infant and mature macaque monkeys. All varieties except 2/3A:3
occurred with regularity in our impregnations from a variety of ages.
B: Diagram summarizing findings from our previous studies (Lund,
1987; Lund et al., 1988; Lund and Yoshioka, 1991). The diagram shows
the pyramidal neuron (five cells to the left of the diagram) and local
circuit neuron (seven numbered varieties to the right of the diagram)
projections from deeper layers to layers 1-2/3A of area V1. At the upper
left, the lateral dimensions of a single blob territory is drawn to scale
with the lateral extent of axon and dendritic fields of the neurons
diagrammed in A and B.
absence in layer 3B may indicate a special role at this
depth in the cortex.
Martin et al. (1989) have recorded and filled intracellularly with horseradish peroxidase a layer 1 neuron in the
cat visual cortex with morphology similar to our variety
1:1 neurons. Its axon contacts and dendritic inputs were
examined by EM, and it was concluded that it both
projected to and received input from pyramidal neurons
(whose apical dendrites and axon processes make up a
major part of the layer 1 neuropil). Functionally, the
neuron was a simple, orientation-selective but nondirectional neuron. Because layer 1 has afferents from a
number of extrinsic sources as well as lateral projections
from pyramids in the superficial layers, these layer 1 local
circuit neurons may share these inputs with the pyramidal
neurons and govern the responsiveness of their apical
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
Fig. 11. Neuron of layer 4B, variety 4B:5 (for further illustration of
this neuron type, see Lund and Yoshioka, 1991). This neuron makes a
rising, axonal projection specifically to layers 1-2/3A. Golgi-rapid
impregnation from the outer operculum of V1 of a 3-week-old M.
nemestrina. Scale bar 5 50 µm.
dendrites to these various afferents. The dimensions of the
axons of the layer 1 cells suggest that this modulation is
across a patch width.
Local modulation within patch boundaries. It is
known that orientation preference can change through 90°
121
Fig. 12. Top: Patchy connections of pyramidal neurons in the
superficial layers of macaque V1 (pial surface to the top, base of layer 3
to the bottom). The scale of change in orientation preference across the
cortex is shown along the top; the pyramidal neurons are drawn to
scale with the change of orientation preference. Pyramids centered in
patches marked A respond best to stimulus orientations near the
vertical; those centered in patches marked B respond best to stimulus
orientations near horizontal. The ‘‘stepping’’ connectivity can start at
any point in the orientation sequences across the cortex, but interconnected patches center on regions of common orientation preference;
the individual connectional patch size does not grow larger than about
250 µm in diameter. Bottom: Superficial layer medium- and widearbor basket neuron connections. The cortex is oriented as in the
diagram above; we propose that entering excitatory afferents (arrows
entering base of center column A) drive both pyramidal neurons and
wide-arbor inhibitory basket cells in layer 3B; layer 3B pyramidal
neurons send rising excitation to pyramidal neurons and mediumarbor basket neurons in layers 2/3A. The wide-arbor and mediumarbor basket neurons of center column A have axon arbors that reach
into neighboring B columns of orientation preference, unlike those of
column A. We propose that, in the B columns, the A basket neurons
inhibit both pyramidal neurons and like-kind basket neurons. This
architecture is presumed to be a continuum across the cortex, and it
implies that only one set of patches can be fully active at any one time,
because their activity will suppress surrounding, unlike territory.
Electron microscopic (EM) studies of synaptology have demonstrated,
in at least the cat V1, that wide-arbor basket neurons have terminals
on both pyramidal neuron somata and proximal dendritic segments as
well as on other basket neurons of the same type (Kisvarday et al.,
1993); EM studies have also shown that the lateral connections of
pyramidal neurons target mainly pyramidal neurons and, as well,
interneuron surfaces (Rockland, 1985; McGuire et al., 1991). Other
relationships hypothesized in this figure need to be confirmed.
across a lateral distance equivalent to a connectional
patch. The double-bouquet or bipolar cells (variety 2/3A:7)
have vertical axon arbors that are narrower than the
pyramidal neuron connectional column and, thus, can
exert influence within this functional gradient; such cells
have been frequently associated with the calcium-binding
proteins calbindin and calretinin and may also contain
CCK or tachykinin as well as GABA (DeFelipe et al., 1990;
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J.S. LUND AND C.Q. WU
DeFelipe, 1993; Lund and Lewis, 1993; Condé et al., 1994;
Yan et al., 1995). It is clear that these neurons may vary
widely in the amount of these substances in the cell and its
processes; the level can vary depending on species, on age,
on cortical area or subcompartments within single areas,
and on activity level of the cell (Hendry and Carder, 1993).
There is reason to believe that there may be different types
of these neurons with forms that are closer to bipolar
morphology with different synaptic relationships (Peters,
1984a; Somogyi and Cowey, 1984); in monkey, however, the
synapses of double-bouquet cells appear to have symmetric (type 2; generally associated with axons of GABAergic
cells) morphology; they synapse about equally on spines
(probably those of pyramidal neurons) and on dendritic
shafts, which may belong to other local circuit neurons
(DeFelipe et al., 1990). The narrow arbor of individual
double-bouquet cell axons may enable a very fine scale of
modulation across the cortical map, even if the neurons
themselves are continuously distributed.
Another candidate for intracolumnar modulation is the
neurogliaform cell (variety 2.3A:4). We have previously
found neurogliaform cells in layer 4B (variety 4B:4 of Lund
and Yoshioka, 1991), and they have been described as a
common component of the cerebral cortex (Fairén et al.,
1984; Jones, 1984) in general. These cells should not be
confused with small local circuit neurons of layer 4C,
which we have called variety 4Cb:1 (Lund, 1987) and
which we believe to be the same as the ‘‘clewed’’ cells of
Valverde (1971). The neurogliaform cells have much finer
axons than this layer 4C neuron variety, and their axons
lack its large diameter dilations. There is, however, a
resemblance between neurogliaform cells and the layer 1
neuron (variety 1:1), but, again, the layer 1 neuron has
somewhat larger diameter boutons on its axon processes
than the neurogliaform cells.
Different sets of feed-forward, local circuit neuron axon
projections accompany the specific relays of different populations of layer 4C spiny stellate neurons to layers 4B, 4A,
and 3B (Lund, 1987; Lund and Yoshioka, 1991). Because
layer 4B has pyramidal neuron projections to layer 3B and
above, and layer 3B pyramids project to layers 1-2/3A, it
might be expected that there would be feed-forward inhibitory relays accompanying these excitatory projections.
Martin et al. (1989) observed GABAergic contacts on the
soma and proximal dendrites of the cat layer 1 cell they
studied. Inhibition of these layer 1 local circuit neurons, if
it produces disinhibition of the pyramidal neuron apical
dendritic arbors in layer 1, could be a means of bringing
the layer 1 inputs into the sum of events affecting the firing
of the parent pyramidal neurons; the source and drive for
the inhibitory synapses on these layer 1 local circuit
neurons is therefore of some importance. Figures 10B and
13A show the sources of inhibition we have been able to
find that enter layer 1 and that might cause disinhibition
of pyramids via inhibition of layer 1 GABAergic cells; local
circuit neurons in layers 5A (variety 5A:4), 4B (variety
4B:5), perhaps 4A (variety 4A,3B:9), and double-bouquet
cells of 2/3A (variety 2/3:5) are all candidates for such
action.
The interneurons with rising columnar axons (varieties
4B, 4A, 3B, 2/3A:2; see Fig. 11) form a continuum of axon
projections and dendritic arbors from layer 4B upward to
the base of layer 1 and these could provide one source of
feed-forward inhibition to layers 2/3. The axons of the
deeper columnar cells have sparser terminal arbors near
the top of layer 3A, whereas more superficial columnar
cells in 2/3A, have a robust axon at the same level, but
Fig. 13. A: Diagram illustrating possible sources of rising ‘‘feedforward’’ columnar inhibition (black dots are numbered interneurons
in layers 4A-3B, 4B, and 5A) directed at local circuit neurons in layers
1–3A (double bouquet, solid oval; chandelier, open squares; layer 1,
solid dots, 1.1), which, themselves, provide direct inhibition to pyramidal neurons. The action of these rising, inhibitory connections is
suggested to be disinhibitory, allowing the pyramids to respond to
rising excitatory afferents (not shown) from the same deeper layers.
The columnar neurons (double squares) are suggested to inhibit
chandelier cells (see B). For further discussion, see text. B: Diagram of
proposed intracolumnar, ‘feed-forward’ disinhibition of pyramidal
neurons involving columnar and chandelier local circuit neurons. In
this circuit, the columnar cells (double squares) are suggested to
inhibit chandelier neurons (single squares), thereby disinhibiting the
pyramidal neurons and allowing them to respond to incoming excitation. Note that the rising intracolumnar excitation provided by
pyramids is suggested to contact both columnar cells and other
pyramids. Laterally running pyramidal neuron collaterals of the patch
system, on the other hand, are suggested to contact chandelier
neurons and pyramids, not the columnar cells. We have proposed
earlier (Lund et al., 1995) that, as the weight of this lateral input
increases, it will have a net inhibitory effect (via the chandelier cells)
on the pyramidal neurons. It should be noted that, in addition to spiny
stellate neurons (open circles), local circuit neurons send projections
out of divisions of 4C; these could inhibit the chandelier neurons
controlling the layer 4B and 3B pyramids (Lund, 1987), i.e., disinhibiting the pyramidal neurons. For further discussion, see text. C: Model
for directional surround suppression of nondirectional layer 2-3 neuron responses. Although neurons of layers 2-3 are not direction
selective in the macaque monkey, surround stimulation of the same
orientation preference and direction of motion as a center stimulus
suppresses responses to the center stimulus (Allman et al., 1990); the
opposite direction of motion in center and surround preserves the
response to the center stimulus. In layer 4B, however, cells can have
true direction selectivity to center stimulus motion; here again,
surround stimulation matched in direction and orientation is suppressive. In this model, layer 4B pyramids in the cortex activated by the
surround send laterally traveling excitation to those center pyramidal
and chandelier neurons (open squares) of similar direction and
orientation specificities. When the weight of the surround input rises
sufficiently, the chandelier neuron inhibition begins to suppress 4B
local pyramidal neurons. The 4B pyramids provide excitatory drive to
4B columnar neurons (double squares), whose rising axons inhibit
superficial layer chandelier neurons. If the 4B pyramids are prevented
from firing by matching center and surround stimulation, then
activation of the local columnar cells is prevented; in the absence of
inhibition, the layer 2-3 chandelier cells remain active and suppressive as the surround input from layer 2-3 pyramids reaches the layer
2-3 center cells. On the other hand, if the layer 4B pyramids are
activated by a center stimulus of one direction of motion and the
surround input is of the opposite direction, then the surround input is
ineffective in silencing these center-driven, directionally specific 4B
pyramids; their activity drives columnar cells that inhibit chandelier
cells in layers 2-3, allowing the nondirectional layer 2-3 pyramids to
continue to respond to lateral input from the surround of the same
orientation but of opposite direction. Although there is EM evidence
for the contacts between the chandelier neuron axon and pyramidal
neuron axon initial segments (Somogyi et al., 1982), for layer 1 neuron
to pyramidal neuron contacts, at least in the cat (Martin et al., 1989),
and for lateral pyramidal neuron connections to both pyramids and
interneurons (Rockland, 1985: McGuire et al., 1991), other synaptic
relationships hypothesized in the diagrams of this figure need to be
confirmed.
Contributors to feed-forward inhibition
of layers 1–3A
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
Figure 13
123
124
sparse arbors in layers 3B and 4B. Given their similarity of
form at all depths, these neurons probably have a common
function throughout the depth of the 4B-to-base-1 column.
The diameter of their columnar axon fields (250–350 µm)
is close to that of the patches of lattice-like pyramidal
neuron axon terminals, so they should provide inhibition
to elements within columns of common function. Because
the columnar cell axons do not intrude into layer 1, their
target is unlikely to be pyramidal neuron apical dendrites.
Below, we suggest that a possible target may be the somata
and proximal dendritic segments of chandelier neurons.
It is clear that there are neurons of columnar class with
dendrites restricted to layer 4B (variety 4B:2; see Fig.
10B), whereas, more superficially, there are columnar cells
whose dendrites cross between layers 3B and 2/3A. The
layer 4B columnar cells with dendrites restricted to that
layer are likely to be driven by activity restricted to layer
4B (because more superficial pyramids do not send terminal arbors down into layer 4B). The more superficial
columnar cells can receive input from axons terminating
through the depth of the superficial layers, i.e., their input
is not restricted to axons stratified to any particular depth
(e.g., to axon projections out of layer 4C that target layer
3B). We suggest, therefore, that the columnar interneurons could be one target of local pyramidal neuron axon
arbors at each level in the column, acting as a ‘‘within
column’’ inhibitory modulator but emphasizing upward
projection with the bulk of their axon, i.e., feed-forward
function, within the column width. In layer 3B-2, the
narrow focus of their dendritic fields (approximately 80 µm
diameter field in layer 2/3, much narrower than the local
pyramidal neuron dendritic arbors of approximately 250
µm diameter) suggests that the cells may have very
specifically tuned response properties, because they occupy such a narrow territory within the laterally changing
gradients of orientation specificity, as well as other properties that are characteristic of these superficial layers. This
tight tuning should be reflected in the inhibition that they
exert.
Apart from the columnar interneurons, one other candidate exists for feed-forward inhibition to layers 1-2/3A:
This is variety 4B:5 (see Fig. 10B), which we have already
discussed in relation to contacts on layer 1 cells, and it also
provides terminals to layers 2/3A. It was described previously by Lund and Yoshioka (1991), and an example is
illustrated in Figure 11 from a better impregnated neuron.
The narrow columnar axon arbor rising from layer 4B
clearly favors layers 1 and 2/3A as a terminal zone.
Another feed-forward interneuron projection comes from a
cell located in layer 4A/base of layer 3B, variety 4A-3B:9
(Lund and Yoshioka, 1991; see Fig. 10B), which terminates
in at least layers 2/3A and 3B. The narrow focus of the axon
arbors of these two varieties of neurons within layers 2-3
suggests that they exert an effect on a scale less than the
connectional patch width. They could both synapse upon
the vertically oriented dendritic arbors of other interneurons in layers 1–3A and have a disinhibitory role. In the
case of the layer 4B neuron, the clear focus of the axon
terminals to within layers 1–3A suggests postsynaptic
elements that are restricted to this territory. Figure 13A
suggests possible targets for these feed-forward GABAergic projections (layer 1 neurons, double-bouquet cells, and
chandelier cells), all of which would lessen inhibition on
the pyramidal neurons in the same column.
J.S. LUND AND C.Q. WU
Functional considerations and
hypothetical circuits
Although it has been clear from the earliest EM studies
of cerebral cortex that interneurons are contacted by type
2 GABAergic synapses, the specific cell types linked by
these connections have only been identified in very few
instances (e.g., basket-to-basket neuron contacts; Kisvarday et al., 1993). The difficulty lies in labeling and identifying both pre- and postsynaptic cells prior to examination
by EM. It will therefore take considerable effort to determine whether our suggested circuitry is anatomically
correct. The answers may come from physiological identification and cell-filling experiments rather than from purely
anatomical investigations, especially if clear hypotheses
are built up concerning what physiological properties the
interneurons are expected to display. We feel, therefore,
that it is useful to make some suggestions for circuitry
involving the interneurons we have described. Although
these circuits may not be accurate, they involve principles
of organization that must be considered in cortical function. By suggesting specific circuitry, we may prompt a
hunt to either confirm or refute these particular circuits on
the basis of predicted physiological properties, and this
should advance our understanding of cortical function.
Because this study suggests that feed-forward inhibition
to layers 1 and 2/3A is a possible function of several neuron
varieties, and feed-forward inhibition has been seen in our
earlier studies of layer 4C interneurons, the question
might be asked what function such inhibition might have.
One function could be to release tonic inhibition on the
targets of the interlaminar, rising relays of feed-forward
excitation, allowing the postsynaptic targets to respond to
the feed-forward excitation; tonic inhibition on pyramidal
neurons could be exerted by either basket or chandelier
neurons. It is known that basket neurons contact and
presumably disinhibit one another in the cat (Kisvarday et
al., 1993), but nothing is known of the origins of inhibition
on chandelier neurons; inhibition of the chandelier neurons is unlikely to come from other chandelier neurons,
given the cartridge-like form of their axon terminal arbors.
One possible function for the columnar cells, therefore,
might be to act as inhibitory controllers of the chandelier
neurons, ensuring that local pyramidal neurons are released from their inhibition under appropriate conditions,
e.g., when the column is active. The excitatory drive for the
chandelier neurons could be from laterally spreading,
pyramidal neuron axon collaterals. In a previous study, we
suggested a simple model by which surround stimulation
may change the firing properties of cortical pyramids to
stimuli presented in their classical receptive field (Lund et
al., 1995); the model postulated the existence of a local
circuit neuron that acts as a ‘‘symbiotic’’ inhibitory companion to pyramidal cells and that suppresses the pyramidal
neuron output when driven by high levels of excitatory
input from laterally offset patches of pyramidal neurons;
here, we suggest that this symbiotic companion is the
chandelier neuron and that its activity is also governed by
feed-forward intracolumnar cell inhibition. A diagram of
this suggested relationship between columnar neuron,
chandelier neuron, and pyramids, together with their
afferents, is shown in Figure 13B. The columnar neurons
in layer 4B that project to the superficial layers could be
one route by which the property of directionally specific
surround modulation (Allman et al., 1990) could be brought
LOCAL CIRCUIT NEURONS OF MONKEY VISUAL CORTEX
to bear on the nondirectional neurons of layers 2-3. A
model circuit diagram is shown in Figure 13C, where
surround motion contradirectional to center-field stimulus
motion is permissive to superficial layer pyramid firing,
whereas the same direction of motion in center and
surround would veto superficial layer pyramid activity.
Columnar neurons as well as chandelier neurons are
found in superficial layers of other regions of the cortex,
e.g., prefrontal cortex (Lund and Lewis, 1993), suggesting
that the function of both cells may be universally applicable. Their relays also pass to layer 5B below, perhaps
representing another step in the feed-forward disinhibitory path. In layer 5, interneurons (variety 5B:2; see Lund
et al., 1988; see also Fig. 11B) are found that may be the
counterparts of these superficial cells; they have both a
local arbor in layer 5B and a robust arbor in layer 2/3A,
and these, again, may be the local controllers of chandelier
neurons in layer 5 as well in the superficial layers.
The question of what is feed-forward or feedback clearly
becomes a problem to interpret in the case of layer 5; thus,
for the moment, it may be better to think of the layer 5
interactions with the superficial layers as parts of a single
process (because their pyramids provide reciprocal connections) with lateral connectivity in the superficial layers
and, to a more limited extent, also playing an important
role within layer 5B. We have not observed chandelier
neurons in layer 6 of V1 (Lund et al., 1988), but this may
have been because of the vagaries of our Golgi impregnations; however, the variety 5B:2 cells, which have been suggested to control the chandelier neurons, also do not contribute
more than the weakest axon collaterals to layer 6.
Comparative aspects
It interesting to note that all of the interneurons described in this study are found in superficial layers of
other, nonvisual regions of the macaque monkey (e.g.,
prefrontal cortex; Lund and Lewis, 1993) as well as
occurring in many other mammals, including a variety of
marsupials (Lund et al., 1994; Tyler et al., 1996). We
conclude from this commonality of occurrence that the
mammalian cortex, in at least its superficial layers, has a
universal, basic set of components that can serve as a
substrate either for processing the very first stages of
sensory input or for functions that are much closer to the
cognitive aspects of behavior ascribed to specific regions,
such as those of the frontal pole. It was also found that, in
all areas of the cortex examined in the primate (Levitt et
al., 1993; Lund et al., 1993) and in the visual cortex in
many different mammals (including monotremes and marsupials; Dann and Buhl, 1995; Tyler et al., 1996), the
superficial layer pyramidal neurons exhibit a discontinuous pattern of lateral connectivity. The interneurons,
therefore, form an integral part of this universal cortical
pattern of organization that apparently has remained
little changed over its evolutionary history.
CONCLUSIONS
This study brings to an end our detailed examination of
the interneurons of the macaque primary visual cortex as
seen in Golgi preparations. Despite their apparent complexity in terms of the variety of different forms in each lamina
and their intricate patterns of interlaminar projections,
there is an impression of economy of organization, in that
each form appears to have a particular role, which is
125
defined by its axon morphology, lateral spread, and specific
patterns of intra- and interlaminar projections. It is interesting to consider that, because the GABAergic neurons in
the cortex are only about one-quarter or less of the total
neuron population (Fitzpatrick et al., 1987), the frequency
of any one variety will be quite low; a sparse representation may allow patterns of activity within any one population that can sculpt activity across the much larger
population of pyramidal neurons. The scale of patterned
connections across the cortex, therefore, may be constrained more by the activity of the interneuron populations than by innate specificity of connections between
particular pyramidal neurons. In particular, the interplay
of wide-arbor axon interneurons’ veto and disinhibition by
interneurons with narrower diameter axons could help to
create the connectional column system prenatally
(Yoshioka, 1994). The excitatory interconnections would
then tend to foster commonality of response patterns in
interconnected columns.
ACKNOWLEDGMENTS
Stephen Griffiths and Kesi Sainsbury are thanked for
their expert technical assistance. Christopher Tyler’s critical appraisal of the paper was much appreciated.
LITERATURE CITED
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motion on the responses of neurons in the first and second cortical
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Signal and Sense: Local and Global Order in Perceptual Maps. New
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