Download Functional Connectivity of the Secondary Somatosensory Cortex of

THE ANATOMICAL RECORD 291:960–973 (2008)
Functional Connectivity of the
Secondary Somatosensory Cortex
of the Rat
CHIA-CHI LIAO AND CHEN-TUNG YEN*
Institute of Zoology, National Taiwan University, Taipei, Taiwan
ABSTRACT
The hierarchical relationship of the rat primary somatosensory cortex
(S1) and secondary somatosensory cortex (S2) is controversial. The existence
of a direct thalamocortical projection from ventral posterolateral thalamic
nucleus (VPL) to S2 is a key factor in determining the relative position of S2
in the processing flow. In this study, the inter-connections of forepaw and
hindpaw representations in VPL, S1, and S2 were examined by neuroanatomical tracing and electrophysiological approaches. In the tracing experiments, VPL, S1, and S2 were electrophysiologically identified, and then
iontophoretically injected with biotinylated dextran amine (BDA, a bi-directional tracer). In the double-labeling experiments, two of the following retrograde tracers—BDA, Rhodamine dextran (RD), and/or Fluoro-Gold
(FG)—were injected into homotypical S1 and S2 forepaw representations
simultaneously. In the electrophysiological studies, paired somatic evoked
multiunit responses in S1 and S2 were compared. Our results revealed that:
(1) VPL forepaw and hindpaw neurons projected to corresponding S1 and S2
areas in a parallel and somatotopic manner; (2) very low percentage of double projecting VPL neurons were found, indicating parallel and independent
pathways from forepaw VPL to S1 and S2; (3) forepaw S1 and S2 were symmetrically and reciprocally connected; (4) response latencies of the S1 and
S2 multiunits to forepaw stimulation were in accordance with a direct and
parallel pathway. This study provides further evidence to support the equivalent hierarchy of S1 and S2 in processing sensory information of the
rat. Anat Rec, 291:960–973, 2008. Ó 2008 Wiley-Liss, Inc.
Key words: parallel; primary somatosensory cortex; serial;
ventral posterolateral thalamic nucleus
The peripheral somatosensory information is known to
convey to the contralateral primary somatosensory cortex (S1) and secondary somatosensory cortex (S2).
Although extensive studies have been carried out on
the thalamocortical and corticothalamic circuitry of
the somatosensory system, whether S1 and S2 process
Abbreviations used: Ang 5 angular thalamic nucleus; BDA 5
biotinylated dextran amine; CPu 5 caudate putamen; eml 5
external medullary lamina; ic 5 internal capsule; ml 5 medial
lemniscus; POm 5 posterior medial nucleus; RD 5 rhodamine
dextran; Rt 5 reticular thalamic nucleus; str 5 superior thalamic
radiation; VA 5 ventroanterior thalamic nucleus; VL 5 ventrolateral thalamic nucleus; VM 5 ventromedial thalamic nucleus;
VPL 5 ventral posterolateral thalamic nucleus; VPM 5 ventral
posteromedial thalamic nucleus; ZId 5 zona incerta, dorsal part.
Grant sponsor: National Science Council, Taiwan; Grant
number: NSC 95-2311-B-002-017-MY3.
*Correspondence to: Chen-Tung Yen, Institute of Zoology,
National Taiwan University, No. 1, Roosevelt Road, Sec. 4,
Taipei 106, Taiwan. E-mail: [email protected]
Received 23 January 2008; Accepted 11 February 2008
DOI 10.1002/ar.20696
Published online 30 April 2008 in Wiley InterScience
(www.interscience.wiley.com).
Ó 2008 WILEY-LISS, INC.
CONNECTIVITY OF RAT S2
peripheral information in parallel or serially remains an
issue of contention (Jones, 2007).
Previous animal studies have reported that S2
receives topographic projections from ipsilateral S1 in
monkeys (Jones et al., 1975, 1978; Friedman and Murray, 1986), cats (Jones and Powell, 1968; Manzoni et al.,
1979; Burton and Kopf, 1984), tree shrews (Weller
et al., 1987), squirrels (Krubitzer et al., 1986), mice
(Carvell and Simons, 1987), and rats (Koralek et al.,
1990; Li et al., 1990; Fabri and Burton, 1991). Based on
this line of evidence, and in addition to the welldescribed thalamic ventral posterior complex (VP) projecting densely to S1 (Jones and Powell, 1969b, 1970;
Burton and Jones, 1976; Lin et al., 1979), a hierarchical
scheme of somatosensory transmission pattern was constructed, in which peripheral information is processed
sequentially from VP thalamus to S1 and then to S2.
This hypothesis was supported further by lesion studies, that is, removal of an S1 representation abolished
the somatic evoked response in the corresponding S2
region in macaques and rhesus monkeys (Pons et al.,
1987, 1988; Burton et al., 1990). In contrast, S1 responsiveness was not affected by the elimination of the
homotypical S2 region (Pons et al., 1988). Electrical
studies further supported the notion that S1 provided
sensory information to S2 because S2 neurons
responded to peripheral stimulation at a longer latency
than S1 neurons in rats (Brett-Green et al., 2003, 2004;
Benison et al., 2007).
In contrast, other studies support a parallel processing
of somatic information. Retrograde tracing investigations have shown that a single neuron in the ventral
posterolateral thalamic nucleus (VPL) project to both S1
and S2 in the cat (Andersson et al., 1966; Spreafico
et al., 1981; Fisher et al., 1983). Retrograde degeneration methods also indicated that VP neurons connect
directly to both S1 and S2 in cats and squirrel monkeys
(Jones, 1975; Stevens et al., 1993). Finally, cooling of S1
does not change S2 responsiveness to peripheral stimulation in rabbits, opossums, rats, and marmoset monkeys (Murray et al., 1992; Coleman et al., 1999; Heppelmann et al., 2001; Zhang et al., 2001b). These results
provide an alternative view, that is, S2 received direct
thalamic inputs rather than through a serially organized
path by means of S1.
One hypothesis to explain these divergent findings is
the possibility that serial or parallel processing types
vary among species and/ or different body regions. The
present study used neuroanatomical and electrophysiological approaches to study the connectional patterns
between forepaw and hindpaw VPL, S1, and S2, an important body regions less well studied in the commonly
used animal model, rat, to address this parallel vs. serial
controversy.
MATERIALS AND METHODS
A total of 29 adult Long-Evans rats (250–350 g) of either sex were conducted in accordance with guidelines
approved in the Codes for Experimental Use of Animals
of the Council of Agriculture of Taiwan, based on the
Animal Protection Law of Taiwan. All experimental protocols were approved by the Institutional Animal Care
and Use Committee of National Taiwan University.
961
Anatomical Tracing Study
Anesthesia was induced
Surgical procedure.
with an intraperitoneal injection of sodium pentobarbital
(50 mg/kg). During surgery, the depth of anesthesia was
verified by periodically testing for the absence of pinch
reflex. Supplementary doses were given as necessary.
The animal was mounted on a stereotaxic apparatus
and its core temperature was maintained at 37.58C by a
feedback-controlled heating pad. While referring to the
atlas of Paxinos and Watson (1998), unilateral craniotomies were made to expose the parietal cortical areas immediately above the electrode penetration sites. In the
sections that follow, all stereotaxic coordinates are given
relative to bregma.
Single injections of bi-directional tracer.
A
bidirectional tracer, biotinylated dextran amine (BDA:
2% in distilled water, molecular weight [MW] 10,000,
Molecular Probes, Eugene, OR) was used in the tracing
experiments. To avoid damaging the S1, glass micropipettes (tip size: 25–50 mm, #602500, A-M system, Carlborg, WA) were filled with BDA solution and lowered at
a 30-degree angle toward the VPL (forepaw region: 3
mm lateral, 7 mm posterior, n 5 4 rats; hindpaw region:
3.5 mm lateral, 7 mm posterior, n 5 4 rats) and S2
(forepaw region: 6.0 mm lateral, 4.7 mm posterior, n 5 4
rats). In contrast, the microelectrodes were oriented perpendicularly to the brain surface when targeting S1
areas (forepaw region: 4 mm lateral, 0.5 mm anterior, n
5 4 rats). To ensure the precise location of the injection
sites, forepaw responsiveness was identified by standard
electrophysiological multiunit recording and tested with
light tapping and brushing. In all cases, BDA was deposited iontophoretically (5 mA, positive current; 5 sec on, 5
sec off) for 20 min. To reduce backflow after injection,
the micropipettes were maintained in the injection sites
for 30 min before withdrawing. The wound was sealed
by surgical staples and the animal was allowed to
recover in its home cage.
Double injections of retrograde tracers. For
the retrograde studies, two additional tracers were used:
Fluoro-Gold (FG: 10% in distilled water, Fluorochrome,
LLC, Denver, CO), and Rhodamine dextran (RD: 10% in
distilled water, MW 10,000, Molecular Probes). The forepaw areas of S1 and S2 were identified physiologically
and tracers were then injected per the scheme in Table
1. To deposit these tracers, BDA and FG were injected
iontophoretically, and RD was injected mechanically.
After each injection, micropipettes were kept in place for
30 min to minimize backflow.
Fixation and immunohistochemistry.
After a
period of 4–10 days, animals were anesthetized with an
overdose of sodium pentobarbital (75 mg/kg) and perfused
transcardially with 0.9% normal saline followed by 4%
paraformaldehyde in 0.1 M phosphate buffer at pH 7.4.
The brains were stored overnight at 48C in cryoprotectant
buffer (25% sucrose, 0.1 M phosphate buffer, pH 7.4), and
then sectioned serially in the coronal plane at 50 or 100
mm on a freezing microtome.
In the BDA tracing cases, brain sections were rinsed
three times in phosphate-buffered saline (PBS) and
reacted sequentially with avidin-labeled peroxidase
962
LIAO AND YEN
TABLE 1. Tracer injection schemes for double-labeling of forepaw
representation areas
S1 tracer and locationa
Scheme 1
Scheme 2
Scheme 3
S2 tracer and locationa
N
0A, 4.0L
1.7P, 6.0L
2
1
3
Rhodamine dextran (RD)
Fluoro-Gold (FG)
Rhodamine dextran (RD)
Fluoro-Gold (FG)
Rhodamine dextran (RD)
Biotinylated dextran amine (BDA)
a
Locations are millimeters relative to bregma (A, anterior; P, posterior; L, lateral). S1, primary
somatosensory cortex; S2, secondary somatosensory cortex.
(ABC kit, PK-6100, Vector Laboratories, Burlingame,
CA) for 1 hr and a diaminobenzidine-30% H2O2 solution
for 10–15 min at room temperature. After three rinses
in PBS, sections were placed on gelatin-coated glass
slides, air-dried, mounted in DPX (Fluka, Seelze, Germany), and coverslipped. In double-labeling experiments
with BDA injections, sections were incubated with the
streptavidin-conjugated cyanine dyes Cy2 or Cy3 (1:200
dilution, Jackson ImmunoResearch Lab, West Grove,
PA) for 1 hr at room temperature.
Data analysis. A 6A Zeiss microscope (Axioplan 2)
equipped with a Nikon digital camera (Coolpix 5000) was
used to capture brightfield BDA images. An Olympus
DSU spinning disk confocal microscope configured with a
BX61 fluorescent microscope and an Olympus FluoView1000 confocal microscope with an IX81 fluorescent
microscope were used to investigate fluorescently labeled
sections. Labeled fibers and boutons were inspected and
digitally acquired. Labeled profiles were also examined
from line drawing with camera lucida attachment, and
then scanned into Photoshop 7.0 for three-dimensional
reconstructions. To determine the projection patterns,
BDA, RD, or FG were examined with appropriate filters.
Single-labeled and double-labeled cells were counted and
summed across every sixth section to determine the total
number of projecting cells in the VPL. Thus, the ratio or
percentage of dual-projecting VPL neurons was calculated as the number of double-labeled cells divided by the
total number of S1- or S2-projecting cells.
Electrophysiological Experiments
Rats (n 5 7 rats) were
Surgery preparation.
anesthetized with sodium pentobarbital (50 mg/kg,
intraperitoneally). The femoral vein was cannulated for
supplemental doses of the same anesthetic (diluted 1:4)
throughout the experiment as needed. Animals were
mounted on a stereotaxic frame and the body temperature was maintained at 37.58C by a feedback-controlled
heating pad. A unilateral craniotomy was performed to
expose the forepaw area of the S1 (0 mm anterior, 4 mm
lateral) and S2 (1.7 mm posterior, 6.0 mm lateral). A
stainless steel screw was implanted into the skull above
the cerebellum as a reference electrode.
Stimulation and recording procedures.
Electrical stimulation was achieved by needle-electrodes
inserted subcutaneously into the contralateral forepaw
pad. The needle electrodes were connected to a constantcurrent stimulator (Grass, S48, Warwick, RI). Multiunit
response in S1 and S2 were evoked by electrical stimulation (120 rectangular pulses, 500 mA, 2 msec duration,
1 Hz). The recording period was 3 min in total, including 30
sec before and 30 sec after applying the current stimulation.
Responses in S1 and S2 were recorded simultaneously
by using two tungsten microelectrodes (#573400, A-M
systems, Carlsborg, WA). Microelectrodes were lowered
into S1 and S2 areas independently, after both recording
sites were first identified by gentle tapping responses to
the same receptive field in the contralateral forepaw
region. Neuronal activities were transmitted into a multichannel acquisition processor system (MAP, Plexon,
Dallas, TX). Multiunit spike waveforms exceeding 1.5
times the peak-to-peak noise were collected into 1,000msec-long wavelets and further analyzed by using OfflineSorter and NeuroExplorer (Plexon, Dallas, TX). Peristimulation histograms were generated with a bin size
of 1 msec. A ‘‘boxcar’’ filter (with a width of three bins)
was used for postprocessing. Multiunit responses were
normalized as Z scores (Tsai et al., 2004). Briefly, the 50msec period before stimulation was used as the baseline
period. The mean firing rate and standard deviation of the
50 bins in this baseline period were calculated. All bin
values were transformed to Z scores according to the
mean and standard deviation of the baseline period. A
99% confidence level (Z > 2.33) was used for identifying
the responsiveness. The initial latencies, peak latencies,
and half-maximum durations of the evoked multiunit
responses in S1 and S2 were compared by a paired t-test.
Histology. At the conclusion of the experiment, S1
and S2 recording sites were marked with electrolytic
lesions (100 mA, 15 sec). The animal was deeply anesthetized with an overdose of pentobarbital (75 mg/kg) and
then perfused through the ascending aorta with 0.9% saline followed by 10% formalin. The brains were stored
overnight at 48C in a cryoprotectant buffer (25% sucrose,
0.1 M phosphate buffer, pH 7.2) and then sectioned at
100 mm thicknesses. Serial sections were mounted on
gelatin-coated slides, followed by Nissl staining. The
lesion sites and recording tracks were documented with
camera lucida drawings.
RESULTS
Thalamocortical Projection From VPL
When BDA was injected into the VPL forepaw area (n
5 4), labeled processes and terminals were easily found
in ipsilateral cortical areas (Fig. 1). In S1, fine-caliber
thalamocortical fibers and terminals with small boutons
form two dense plexuses in vertical cortical columns:
one in layer IV, and the other in layer VI (Fig. 1B).
Intermixed spinous (terminaux) and bead-like (en passant) terminals were attached to these labeled afferent
963
CONNECTIVITY OF RAT S2
Fig. 1. An example of BDA injected in the VPL forepaw area. A:
Photomicrograph of a coronal section showing the injection site. B:
Photomicrograph of BDA-labeled terminals in the ipsilateral S1. Amplified terminal boutons are shown in the insert. C: Photomicrograph of
BDA-labeled terminals in ipsilateral S2. D: Coronal planes depicting
the distribution of BDA-labeled terminals in S1 and S2. Arrowheads
indicate the demarcation between layers four and five of the cortex.
BDA, biotinylated dextran amine; S1, primary somatosensory cortex;
S2, secondary somatosensory cortex; VPL, ventral posterolateral
thalamic nucleus. Scale bar 5 500 mm in A–C, 10 mm in both inserts.
TABLE 2. Projections from bidirectional tracers labeling to ipsilateral brain regionsa
Injection site
Representation
Projection
S1 location
S2 location
VPL location
Fig. 1 (N 5 1)
Fig. 2 (N 5 1)
Fig. 3 (N 5 8)
VPL
VPL
VPL
TC
TC
TC
0.7A-1.3P
0.4A-1.3P
0.7A-2.2P
1.3P-1.8P
2.6P
1.3P-2.8P
----
Fig. 4 (N 5 1)
S1
Forepaw
Hindpaw
Forepaw and hindpaw,
summary
Forepaw
Fig. 5 (N 5 1)
S2
Forepaw
Fig. 6 (N 5 8)
S1 & S2
CC
CT
TC
CC
CT
TC
CT
TC
CT
TC
---1.0A-2.0P
------
1.3P-2.5P
---------
-2.8P-3.3P
2.6P-3.5P
-2.56P-3.6P
3.1P-3.6P
2.3P-3.6P
2.3P-3.6P
2.6P-4.1P
3.1P-4.1P
S1 forepaw summary
S2 forepaw summary
a
Locations are millimeters relative to bregma (A, anterior; P, posterior). TC, thalamocortical projections; CT, corticothalamic projections; CC, corticocortical projections; S1, primary somatosensory cortex; S2, secondary somatosensory cortex;
VPL, ventral posterolateral thalamic nucleus.
axons. A comparable labeling was also observed in S2
(Fig. 1C): two clusters composed of fine axons and small
varicosites were also located in layers IV and VI. The
distribution of labeled terminations in cortical region
was depicted using camera lucida drawings (Fig. 1D)
and was summarized in Table 2.
In a second series of experiments, BDA was deposited
into the hindpaw region of VPL (n 5 4) and a similar
cortical projection pattern was observed (Fig. 2). Labeled
fibers extending from thalamus terminated in ipsilateral
S1 and S2 regions, at locations summarized in Table 2.
As in the VPL forepaw injection experiments, labeled
processes and terminals were divided into two clusters
located in both layers IV and VI. Although the labeled
terminals in S2 (shown in Fig. 2C) were less dense than
in the forepaw experiments, labeled boutons could still
be clearly discerned and characterized by fine-caliber
fibers with boutons both terminaux and en passant.
964
LIAO AND YEN
Fig. 2. An example of BDA injected in the VPL hindpaw area. A:
Photomicrograph of a coronal section showing the injection site. B:
Photomicrograph of BDA-labeled terminals in the ipsilateral S1. Amplified terminal boutons are shown in the insert. C: Photomicrograph of
BDA-labeled terminals in ipsilateral S2. D: Coronal planes showing the
distribution of BDA-labeled terminals in S1 and S2. Arrowheads indicate the demarcation between layers four and five of the cortex.
Abbreviations as in Figure 1. Scale bar 5 500 mm in A,B, 10 mm in C
(and insert).
The thalamocortical fibers ascending from VPL to
either S1 or S2 were examined. They first passed through
caudate putamen, and then reach the S2. These labeled
thalamocortical fibers can further be traced toward S1.
Projection destinations in ipsilateral cortical areas arising from VPL forepaw and hindpaw neurons are summarized in Figure 3 and Table 2. Two somatosensoryrelated regions were heavily labeled, corresponding to
the traditionally defined S1 and S2 (Fig. 3A). When the
distribution of the ascending terminals in the ipsilateral
cortical area were plotted on the two-dimension plane
(Fig. 3B), both S1 and S2 are characterized by somatotopic organization of VPL forepaw and hindpaw neuron
terminations. However, in addition to S1 and S2, a third
area located caudally was also noted to be labeled with
VPL projecting terminations. All three regions received
direct inputs from VPL forepaw and hindpaw neurons.
ranging from 2.6P to 3.2P (Fig. 4D). In the dorsal thalamus, a dense plexus of small labeled axons and varicosites were located in the medial VPL and BDA-labeled
VPL cells were mingled with those terminals ranging
from 2.6P to 3.3P. Corticothalamic terminals were also
found in the posterior medial nucleus and the reticular
thalamic nucleus. Two types of terminals were found in
the posterior medial nucleus: one of large size (3–10
mm), and the other of smaller size (0.5–0.8 mm). Furthermore, the S1 forepaw representation also projected to
contralateral S1 and S2 regions.
Thalamocortical and Corticocortical
Connections of S1
Input and output connections of the S1 forepaw region
were traced by BDA injections (Fig. 4). After injection,
labeled terminals and cells were easily found in ipsilateral S2 and VPL (Fig. 4B–D). In S2, labeled axons were
noted in every layer, but concentrated more in layer II/
III. Several retrogradely labeled cells were distributed in
layer II/III and VI. Comparable termination was
observed in another cortical area, located at 3.5 mm posterior (3.5P) and 6.5 mm lateral (6.5L). In addition, labeled terminals were found around the rhinal sulcus
Thalamocortical and Corticocortical
Connections of S2
When BDA was injected into S2 forepaw region (Fig.
5), BDA-labeled cells and fibers with both terminaux
and en passant terminals were observed in ipsilateral
S1, particularly in layers II/III and VI (Fig. 5B). In addition to S1, labeled profiles were also found at approximately 3.6P and 8.0L, and perirhinal cortex ranging
from 3.1P to 3.6P. The medial VPL contained a labeled
plexus composed of very thin axons with irregularly
arranged terminals (both terminaux and en passant),
analogous to the S1 forepaw axons (Fig. 4C). It is important to note that retrogradely labeled cells existed
within VPL and were intermixed with the labeled corticothalamic fibers. These S2-projecting VPL cells were
located in areas ranging 3.1P to 3.6P. The ipsilateral
posterior medical nucleus and reticular thalamic nucleus
were labeled simultaneously, with the axons in the
Fig. 3. Summary of the labeled terminal distributions after BDA was
injected into VPL forepaw (arrowhead, green asterisk, n 5 4) and hindpaw (arrow, red asterisk, n 5 4) regions. A: Anteroposterior plane
depicting the thalamocortical terminations in the ipsilateral S1 and S2.
B: Two-dimensional organization of the labeled terminations in the ipsilateral cortical region. The green squares represent thalamocortical
terminations extending from VPL forepaw neurons, and the red squares
symbolize the projecting terminations of VPL hindpaw neurons. Note
that both ipsilateral S1 and S2 were topographically labeled. BDA, biotinylated dextran amine; A, anterior; POm, posterior medial nucleus; L,
lateral; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; VPM, ventral posteromedial thalamic nucleus.
966
LIAO AND YEN
Fig. 4. An example of BDA injected into S1 forepaw area. A: Photomicrograph depicting the injection site. B: Photomicrograph of labeled corticocortical terminations in ipsilateral S2. C: Photomicrograph
of labeled corticothalamic terminations in ipsilateral VPL. D: Camera
lucida drawings of the terminal fields in ipsilateral S2 and dorsal thalamus. Solid circles represent the retrogradely labeled cells, and small
dots mark the labeled terminations. Inserts in B and C are enlarged
views of labeled axons and boutons. BDA, biotinylated dextran amine;
CPu, caudate putamen; ic, internal capsule; Rt, reticular thalamic nucleus; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; VL, ventrolateral thalamic nucleus. Scale bar 5 1 mm in
A–C, 20 mm in inserts.
former carry both large and small terminals, and axons
in the latter are with exclusively small boutons. Furthermore, contralateral S2, but not S1, was labeled with
callosal-extending axons mainly in layer VI.
The distribution of labeled cells and terminations
within dorsal thalamus with BDA injected into S1 and
S2 forepaw regions was summarized in Figure 6. Corticothalamic terminations originating from S1 forepaw
neurons within VPL were mainly located in areas ranging from 2.3P to 3.6P, and the S2 axons terminated in
the medial VPL ranging from 2.6P to 4.1P. Concerning
the retrogradely labeled VPL cells, S1-projecting VPL
cells were chiefly distributed from 2.3P to 3.6P, while
most S2-projecting cells were located at more posterior
level, from 3.1P to 4.1P. These data suggested that S1
and S2 share comparable thalamocortical linking pattern, even though the S1- and S2-projecting VPL cells
were arranged in an antero–posterior manner.
the existence of double-labeled VPL cells were examined
in six rats. Among S1-projecting VPL cells (48–105 neurons per rat), 8.3 6 1.5% (mean 6 SEM) also project to
S2, while 17.4 6 5.4% of S2-projecting cells (22–67 neurons per rat) were double-labeled with S1 projecting
neurons. In total, 5.2 6 0.4% (23 of 443 neurons) of the
labeled thalamocortical neurons projected to both S1 and
S2. It is important to note that these retrogradely
labeled cells, despite S1- or S2-projecting cells, were
roughly distributed in either the central part or the ventral fringe of the VPL. One example—with RD injected
into S1 and BDA injected into S2—is shown in Figure 7.
Merged RD and BDA/ Cy2 staining views show neurons
double-labeled inside the VPL region (arrows and arrowheads). Furthermore, the distribution of S1- and S2-projecting VPL cells along the antero–posterior axis
were shown in Figure 7G. Most S1-projecting cells were
located from 2.3P to 3.3P, while S2-projecting cells were
mainly situated around 3.1P to 3.7P. Among these projecting VPL cells, few S1- and S2-dual projecting cells
were distributed in the intermediate zone, from 3.2P to
3.4P.
Although double-labeled cells represent a low proportion within the total labeled population, the presence of
these cells demonstrate that dual projections from VPL
cells to ipsilateral homotypical S1 and S2 regions do
exist.
Double Projection From VPL to S1 and S2
The above tracing results revealed that VPL neurons
project directly to both S1 and S2. However, whether a
single VPL neuron can provide collateral branches to
both S1 and S2 was yet unknown. To explore this issue,
retrograde tracers were injected into physiologically
identified S1 and S2 forepaw areas in the same rat, and
CONNECTIVITY OF RAT S2
967
Fig. 5. An example of BDA injected into S2 forepaw region. A:
Photomicrograph of the injection site. B: BDA-labeled cells and corticocortical terminals in the ipsilateral S1. C: BDA-labeled corticothalamic termination in ipsilateral VPL. D: Coronal planes showing the
distribution of the labeled cells and terminals in ipsilateral cortex and
dorsal thalamus. Solid circles represent the retrogradely labeled cells,
and small dots mark the labeled terminations. Inserts in B and C are
enlarged view of axons and boutons. BDA, biotinylated dextran amine;
S2, secondary somatosensory cortex; VA, ventroanterior thalamic
nucleus. Scale bar 5 1 mm in A–C; 20 mm in inserts.
Electrophysiological Comparison of S1 and S2
Thalamic Coactivation of S1 and S2
Stimulation-evoked multiunit responses in S1 and S2
were simultaneously recorded by electrical stimulation
applied to contralateral forepaw (n 5 7). All recording
sites in the S1 and S2 were histologically confirmed at
locations in layer V or VI. An example of simultaneous
recorded S1 and S2 evoked multiunit responses are shown
in Figure 8A. The average initial latencies of the evoked
multiunit responses in the S1 and S2 from the seven cases
were 8.6 6 0.5 msec and 6.9 6 0.7 msec, respectively (Fig.
8B, P 5 0.045*, pair t-test). Furthermore, the average
peak latencies were 12.0 6 1.1 msec and 11.9 6 0.9 msec
(P 5 0.685), while the half-maximum durations were 7.1
6 0.9 msec and 8.7 6 0.9 msec (P 5 0. 091).
Direct connections between VPL, S1, and S2 have
been reported in mice, rats, cats, macaques, squirrel
monkeys, and gray squirrels (Rowe and Sessle, 1968;
Jones and Powell, 1969a; Manson, 1969; Jones, 1975;
Spreafico et al., 1981; Fisher et al., 1983; Burton and
Kopf, 1984; Carvell and Simons, 1987; Krubitzer and
Kaas, 1987; Aldes, 1988; Stevens et al., 1993; Pierret
et al., 2000). In the present study, both S1 and S2 were
anterogradely labeled after BDA was injected into forepaw or hindpaw regions. In addition, VPL cells were labeled after retrograde tracers were deposited into either
S1 or S2 forepaw fields, further suggesting the possibility of coactivation. Although both the S1- and S2-projecting VPL cells were found in the medial division of VPL
(forepaw area), S2-projecting neurons were distributed
at a more posterior level than S1-projecting cells, forming a mosaic pattern in the intermediate zone. The phenomenon suggested that VPL simultaneously activates
S1 and S2 through segregative streams, even there are
only a few double-labeled VPL cells (5%).
Our results are in accordance with previous cat studies in that S1- and S2-projecting neurons were colocalized in the VPL, with a low percentage of the neurons
providing bifurcate branches to S1 and S2 (Spreafico
et al., 1981; Fisher et al., 1983; Burton and Kopf, 1984).
However, the distribution of these projecting cells
remained controversial among those investigations.
DISCUSSION
Anatomical and electrophysiological methods were
used to investigate the flow of information processing to
S2. Our major findings were as follows: (1) VPL neurons
provided parallel projections to S1 and S2, (2) very low
percentage of S1- and S2-dual projecting VPL cells were
found, (3) S1 and S2 were reciprocally connected, and
(4) S1 and S2 neurons responded to electrical stimulation of the forepaw with comparable latencies and
response patterns. These results suggest that S1 and S2
participated in the processing of paw sensory information in parallel rather than serially.
968
LIAO AND YEN
Figure 6.
CONNECTIVITY OF RAT S2
Fisher et al. (1983) stated that S1- and S2-projecting
cells coexisted within VPL, and 10% of them activated
S1 and S2 by means of collateral axons. However, Spreafico et al. (1981) found that most S1-projecting cells were
located in the VP core region, while S2-projecting neurons were found in the ventral fringe, the shell division,
of the VPL. Among these projecting VPL cells, 13–20%
had dual projections and were found only within the
ventral shell region, where they were intermixed with
VPL cells that projected solely to S2. Although no
obvious demarcation of core and shell divisions has been
reported in the rat, double-labeled cells in the present
study were mainly positioned in two locations: one is in
the central VPL, and the other is in the ventral border.
This phenomenon may suggest the possibility of anatomical segmentation of the VPL in the rat.
In this study, when the contralateral forepaw was
stimulated, the average initial latency of evoked multiunit response of S2 neurons was significantly shorter
than S1 neurons, but no significant difference existed
between peak latencies and half-maximum duration of
S1 and S2 responsiveness. To rationalize this result, we
observed the path taken by the BDA-labeled thalamocortical axons stemming from the VPL to cortical areas.
The extending fibers ascended through caudate putamen
and then entered either S1 or S2 directly. The distance
between VPL neurons and their S2 destination is
shorter than the path taken by VPL-S1 axons. Our
result is consistent with several previous studies
(Woolsey and Wang, 1945; Heppelmann et al., 2001;
Kwegyir-Afful and Keller, 2004), which showed that S1
and S2 neurons responded to peripheral stimulation
with similar peak latencies in rabbits and rats. However,
Brett-Green et al. (2003, 2004) and Benison et al. (2007)
examined epipial-evoked potentials when stimulating a
rat’s whisker and other body regions, and found a much
longer latency of evoked response in S2 than in S1. The
discrepancy may be due to variations in stimulation modality or recording methods. In the current study, electrical stimulation was applied to the forepaw, while
studies by Brett-Green et al. (2003, 2004) and Benison
et al. (2007) used mechanical stimulation. However,
Kwegyir-Afful and Keller (2004) examined S1 and S2
responses evoked by whisker deflection, and found that
S1 and S2 responded with similar peak latencies. In
addition, we investigated the evoked S1 and S2
responses by multiunit recording, whereas Brett-Green
et al. used epipial-evoked potential. Although the disagreement may result from different recording methods,
Heppelmann et al. (2001) also examined S1 and S2
response latencies by measuring cortical surface potentials, and found similar electrical-evoked response latencies in S1 and S2. The effect of recording methods or
stimulation modalities on measurements of relative
latencies needs further investigation.
Fig. 6. Summary distribution of labeled cells and terminations with
BDA injected into S1 (n 5 4) and S2 (n 5 4) forepaw regions. The
green color represents results from S1 injections and red color symbolizes the results from S2 injections. The solid circles indicate the
distribution of retrogradely labeled cells and small dots mark the projecting terminations. Note that the labeled cells and terminals were
observed within the medial VPL and POm after S1 and S2 injections.
969
S1 and S2 hierarchies have been studied by inactivation strategies in many species. Functionally, S2 seemed
to be equivalent with S1, because it maintained its
responsiveness when S1 was reversibly inactivated in
rabbits, opossums, prosimian primates, tree shrews,
marmoset monkeys, and rats (Woolsey and Wang, 1945;
Garraghty et al., 1991; Murray et al., 1992; Coleman
et al., 1999; Heppelmann et al., 2001; Zhang et al.,
2001b). When the treatment was reversed in cat and
marmoset monkey studies, S1 was similarly found to
maintain its responsiveness after S2 inactivation
(Turman et al., 1995; Zhang et al., 2001b). Somatic
evoked responses of most neurons were unaffected,
though a portion of neurons showed some reduction. The
reduction may be induced by the reciprocal connections
between S1 and S2 (Burton et al., 1990; Krubitzer and
Kaas, 1990; Schwark et al., 1992; Barbaresi et al., 1995;
Cauller et al., 1998; Karhu and Tesche, 1999; Zhang
et al., 2001b). The investigations suggest that S1 and S2
occupy comparable position in the somatosensory information flow in most mammals, including some primates.
Cortical Connection Between
Somatosensory-Related Fields
Reciprocal corticocortical connections between homotypical S1 and S2 regions have been well established
(Burton, 1984; Alloway and Burton, 1985; Krubitzer and
Kaas, 1990; Schwark et al., 1992; Catania and Kaas,
2001; Disbrow et al., 2003). Despite the mutual connection, S2 was argued to be superior to S1 in hierarchy,
based on the anatomical relationship. In marmoset and
cat, S1 projects to middle layers in S2, while S2 projects
to superficial layers of S1 (Krubitzer and Kaas, 1990;
Schwark et al., 1992; Burton et al., 1995). This projecting pattern has been established as hierarchical conveyance across cortical regions in the visual system, a serial
processing model (Felleman and Van Essen, 1991). However, Barbaresi et al. used light and electron microscopy
to study the laminar distribution of corticocortical projecting terminations between S1 and S2 in cats (Barbaresi et al., 1994, 1995). They stated that the origin
and termination of the two corticocortical projections
reciprocally connecting S1 and S2 in cats showed similar, although not identical, laminar organization: both
corticocortical axons terminated mostly in the supragranular layers. In our study, a symmetrical laminar
arrangement of reciprocal projections between S1 and
S2 was found, with analogous anatomical organization
of the horizontal connection between S1 and S2. No
clear hierarchical relationship was seen between the S1
and S2 of the rat paw regions.
In addition to S1 and S2, the parietal ventral (PV) has
been known to be the third cortical region in processing
somatosensory information (Jones and Powell, 1968;
However, only terminals were found in Rt. BDA, biotinylated dextran
amine; Ang, angular thalamic nucleus; eml, external medullary lamina;
ml, medial lemniscus; Rt, reticular thalamic nucleus; S1, primary
somatosensory cortex; S2, secondary somatosensory cortex; str,
superior thalamic radiation; VM, ventromedial thalamic nucleus; ZId,
zona incerta, dorsal part.
970
LIAO AND YEN
Fig. 7. A representative example of labeled thalamic neuronal fibers
and terminals with RD injected into S1 forepaw region and BDA injected
into S2 forepaw region. A: RD-labeled, S1 projecting cells within the
VPL. B: BDA/ Cy2-labeled, S2 projecting cells within the VPL. C: Merged
photo showing the double-labeled cells. Note that the double-labeled
cells were located within the central VPL (arrowheads), or the ventral
fringe (arrows). D–F: Amplified RD-, BDA/ Cy2-labeled VPL cells and
merged photo (arrowhead). G: Numbers of RD-labeled VPL cells (open
bars) and BDA/ Cy2-labeled VPL cells (gray bars). The black bars represent the numbers of RD- and BDA/ Cy2 double-labeled VPL cells. BDA,
biotinylated dextran amine; VPL, ventral posterolateral thalamic nucleus;
RD, rhodamine dextran; Cy2, streptavidin-conjugated cyanine dyes; S1,
primary somatosensory cortex; S2, secondary somatosensory cortex; P,
posterior. Scale bar 5 200 mm in A–C, 30 mm in D–F.
CONNECTIVITY OF RAT S2
971
Fig. 8. Electrical-evoked multiunit responses recorded in S1 and
S2 when peripheral stimulation was applied at time 0 to contralateral
forepaw (500 mA, 2 msec, 1 Hz, 2 min). A: An example of initial latencies of evoked response: 8 msec in S1 and 7 msec in S2. Peak latencies were 14 msec in S1 and 11 msec in S2. Half-maximum durations
were 11 msec in S1 and 9 msec in S2. B: Comparison of evoked mul-
tiunit responses in S1 and S2 (n 5 7). The average initial latencies
were 8.6 6 0.5 and 6.9 6 0.7 msec, the peak latencies were 12.0 6
1.1 and 11.9 6 0.9 msec, and the half-maximum durations were 7.1
6 0.9 and 8.7 6 0.9 msec in S1 and S2. *, P < 0.05; n.s., no significant difference. S1, primary somatosensory cortex; S2, secondary
somatosensory cortex.
Burton and Kopf, 1984; Koralek et al., 1990; Krubitzer
and Kaas, 1990; Li et al., 1990; Fabri and Burton, 1991;
Krubitzer et al., 1995; Disbrow et al., 2000; Qi et al., 2002;
Disbrow et al., 2003). The PV was reported to link reciprocally with ipsilateral VPL, S1, and S2 (Krubitzer and
Kaas, 1990; Disbrow et al., 2000; Qi et al., 2002; Disbrow
et al., 2003). A similar organizational arrangement
occurred in rats (Koralek et al., 1990; Li et al., 1990; Fabri
and Burton, 1991; Brett-Green et al., 2004; Benison et al.,
2007). In the rat, PV was described as a complete, mirrorsymmetric area of the body surface, with the limb representations joining neighboring S2 (Fabri and Burton,
1991; Remple et al., 2003). Therefore, the relative organization of PV is difficult to identify by the present neuroanatomical method due to the adjacent arrangement of S2
and PV. However, Benison et al. (2007) recently mapped
the rat somatosensory area using epipial potential recording, and claimed that the S2 field is somatotopically
organized, with the body area located caudal to the S1
barrel fields. Forepaw is represented in S2 at 3.5 mm posterior and 6 mm lateral to bregma, and in PV (lateral to
S1 barrel field) at 1.5 mm posterior and 9 mm lateral to
bregma. This arrangement is inconsistent with the previous view that S2 is an upright rattunculus positioned just
lateral to S1 (Chapin and Lin, 1984; Carvell and Simons,
1987; Fabri and Burton, 1991; Remple et al., 2003). In our
study, three locations were labeled after anterograde tracers were injected into VPL forepaw area. One was located
in the traditionally defined S1 forepaw area, another at
1.5–2.0 mm posterior and 9 mm lateral, identified as S2 in
the current and previous studies (Carvell and Simons,
1987; Fabri and Burton, 1991; Remple et al., 2003), and
the third at 3.5 mm posterior and 7 mm lateral. When
compared with the arrangement reported by Benison
et al. (2007), our ‘‘S2 forepaw area’’ is located in their ‘‘PV
forepaw area,’’ while the caudal labeling area corresponds
to their ‘‘S2 region’’. Nevertheless, we found that the den-
sity of labeled thalamocortical terminations in the rostral
‘‘S2’’ is much higher than the caudal ‘‘S2’’, therefore, it
might be reasonable to recognize the rostral one as ‘‘S2
forepaw area,’’ despite that the labeled region may be
composed of S2 and PV as previously described. In addition to the thalamocortical terminations, the caudallabeled region also received corticocortical inputs from S1
and S2 neurons. The results suggest that the area may
also be involved in processing somatosensory information,
although the definite role remains to be proven.
Hierarchical View of Somatosensory Flow
Observations favoring serial hierarchical processing
came from a sparse projection from VPL to S2, and a
dense projection to S1 in macaques (Kaas, 1983; Manzoni et al., 1984; Friedman and Murray, 1986; Krubitzer
and Kaas, 1990), coupled with observations of thick corticocortical projections from S1 to S2 in many mammals
(Akers and Killackey, 1978; Kunzle, 1978; Wise and
Jones, 1978; Friedman et al., 1980; Jones and Friedman,
1982; Jones, 1983; Manzoni et al., 1990; Fabri and Burton, 1991; Burton et al., 1995). The assumption was
strengthened by ablation experiments in macaques,
which demonstrated that the removal of the posterior
parietal cortex (area 3a, 3b, 1, and 2) eliminated responsiveness in the S2 representation, although there was
no detectable effect on S1 responsiveness when the operation was reversed (Pons et al., 1987; Burton et al.,
1990). However, these results conflicted with the inactivation findings described above (Woolsey and Wang,
1945; Garraghty et al., 1991; Murray et al., 1992; Coleman et al., 1999; Heppelmann et al., 2001; Zhang et al.,
2001b), perhaps because the latter studies used reversible cooling instead of irreversible aspiration, or it could
be due to the differences between species.
972
LIAO AND YEN
A recently developed evolutionary hypothesis suggests
that a prominent change of somatosensory organization
occurred when the Old World macaques diverged from
other primates along the evolution path (Kaas, 2004). In
the higher-primates, S2 lost the direct thalamic afferents and depend on the corticocortical inputs from ipsilateral S1 for activation. Summing the various aforementioned studies, results favoring serial transmission
were performed mostly on macaque and rhesus monkeys
(Pons et al., 1987, 1988, 1992; Burton et al., 1990), while
investigations supporting the parallel view used nonprimitive primates and other mammals, including rats,
cats, marmoset monkeys, tree shrews, and opossums
(Spreafico et al., 1981; Fisher et al., 1983; Murray et al.,
1992; Turman et al., 1995; Coleman et al., 1999; Heppelmann et al., 2001; Zhang et al., 2001a,b; Kwegyir-Afful
and Keller, 2004). Our results from rats further support
the distinction between serial somatosensory processing
in higher primates and parallel somatosensory processing in other mammals.
In conclusion, by showing direct layer IV thalamocortical projection from VPL to S1 and S2, reciprocal symmetrical connection between S1 and S2, and similar
response latencies and patterns to paw stimulation, the
present study provided another evidence in support of
the parallel processing of somatosensory flow by the S1
and S2 in the rat forepaw and hindpaw inputs.
ACKNOWLEDGMENT
We thank Professor Rick CS Lin for critical comments.
LITERATURE CITED
Akers RM, Killackey HP. 1978. Organization of corticocortical connections in the parietal cortex of the rat. J Comp Neurol 181:513–
537.
Aldes LD. 1988. Thalamic connectivity of rat somatic motor cortex.
Brain Res Bull 20:333–348.
Alloway KD, Burton H. 1985. Submodality and columnar organization of the second somatic sensory area in cats. Exp Brain Res
61:128–140.
Andersson SA, Landgren S, Wolsk D. 1966. The thalamic relay and
cortical projection of group I muscle afferents from the forelimb of
the cat. J Physiol 183:576–591.
Barbaresi P, Minelli A, Manzoni T. 1994. Topographical relations
between ipsilateral cortical afferents and callosal neurons in the
second somatic sensory area of cats. J Comp Neurol 343:582–596.
Barbaresi P, Guandalini P, Manzoni T. 1995. Laminar pattern of
termination of the ipsilateral cortical projection from SII to SI in
cats. J Comp Neurol 360:319–330.
Benison AM, Rector DM, Barth DS. 2007. Hemispheric mapping of
secondary somatosensory cortex in the rat. J Neurophysiol
97:200–207.
Brett-Green B, Fifkova E, Larue DT, Winer JA, Barth DS. 2003. A
multisensory zone in rat parietotemporal cortex: intra- and
extracellular physiology and thalamocortical connections. J Comp
Neurol 460:223–237.
Brett-Green B, Paulsen M, Staba RJ, Fifkova E, Barth DS. 2004.
Two distinct regions of secondary somatosensory cortex in the rat:
topographical organization and multisensory responses. J Neurophysiol 91:1327–1336.
Burton H. 1984. Corticothalamic connections from the second somatosensory area and neighboring regions in the lateral sulcus of
macaque monkeys. Brain Res 309:368–372.
Burton H, Jones EG. 1976. The posterior thalamic region and its
cortical projection in New World and Old World monkeys. J Comp
Neurol 168:249–301.
Burton H, Kopf EM. 1984. Ipsilateral cortical connections from the
second and fourth somatic sensory areas in the cat. J Comp Neurol 225:527–553.
Burton H, Sathian K, Shao DH. 1990. Altered responses to cutaneous stimuli in the second somatosensory cortex following lesions
of the postcentral gyrus in infant and juvenile macaques. J Comp
Neurol 291:395–414.
Burton H, Fabri M, Alloway K. 1995. Cortical areas within the lateral sulcus connected to cutaneous representations in areas 3b
and 1: a revised interpretation of the second somatosensory area
in macaque monkeys. J Comp Neurol 355:539–562.
Carvell GE, Simons DJ. 1987. Thalamic and corticocortical connections of the second somatic sensory area of the mouse. J Comp
Neurol 265:409–427.
Catania KC, Kaas JH. 2001. Areal and callosal connections in the
somatosensory cortex of the star-nosed mole. Somatosens Mot Res
18:303–311.
Cauller LJ, Clancy B, Connors BW. 1998. Backward cortical projections to primary somatosensory cortex in rats extend long horizontal axons in layer I. J Comp Neurol 390:297–310.
Chapin JK, Lin CS. 1984. Mapping the body representation in the
SI cortex of anesthetized and awake rats. J Comp Neurol
229:199–213.
Coleman GT, Zhang HQ, Murray GM, Zachariah MK, Rowe MJ.
1999. Organization of somatosensory areas I and II in marsupial
cerebral cortex: parallel processing in the possum sensory cortex.
J Neurophysiol 81:2316–2324.
Disbrow E, Roberts T, Krubitzer L. 2000. Somatotopic organization
of cortical fields in the lateral sulcus of Homo sapiens: evidence
for SII and PV. J Comp Neurol 418:1–21.
Disbrow E, Litinas E, Recanzone GH, Padberg J, Krubitzer L. 2003.
Cortical connections of the second somatosensory area and the parietal ventral area in macaque monkeys. J Comp Neurol 462:382–
399.
Fabri M, Burton H. 1991. Ipsilateral cortical connections of primary
somatic sensory cortex in rats. J Comp Neurol 311:405–424.
Felleman DJ, Van Essen DC. 1991. Distributed hierarchical processing in the primate cerebral cortex. Cereb Cortex 1:1–47.
Fisher GR, Freeman B, Rowe MJ. 1983. Organization of parallel
projections from Pacinian afferent fibers to somatosensory cortical
areas I and II in the cat. J Neurophysiol 49:75–97.
Friedman DP, Murray EA. 1986. Thalamic connectivity of the second somatosensory area and neighboring somatosensory fields of
the lateral sulcus of the macaque. J Comp Neurol 252:348–373.
Friedman DP, Jones EG, Burton H. 1980. Representation pattern in
the second somatic sensory area of the monkey cerebral cortex.
J Comp Neurol 192:21–41.
Garraghty PE, Florence SL, Tenhula WN, Kaas JH. 1991. Parallel
thalamic activation of the first and second somatosensory areas
in prosimian primates and tree shrews. J Comp Neurol 311:289–
299.
Heppelmann B, Pawlak M, Just S, Schmidt RF. 2001. Cortical projection of the rat knee joint innervation and its processing in the
somatosensory areas SI and SII. Exp Brain Res 141:501–506.
Jones EG. 1975. Possible determinants of the degree of retrograde
neuronal labeling with horseradish peroxidase. Brain Res 85:249–
253.
Jones EG. 1983. Lack of collateral thalamocortical projections to
fields of the first somatic sensory cortex in monkeys. Exp Brain
Res 52:375–384.
Jones EG. 2007. The ventral nuclei. In: Jones EG, editor. The thalamus. 2nd ed. New York: Cambridge. p 775–795.
Jones EG, Friedman DP. 1982. Projection pattern of functional components of thalamic ventrobasal complex on monkey somatosensory cortex. J Neurophysiol 48:521–544.
Jones EG, Powell TP. 1968. The ipsilateral cortical connexions of
the somatic sensory areas in the cat. Brain Res 9:71–94.
Jones EG, Powell TP. 1969a. The cortical projection of the ventroposterior nucleus of the thalamus in the cat. Brain Res 13:298–
318.
Jones EG, Powell TP. 1969b. An electron microscopic study of the
mode of termination of cortico-thalamic fibres within the sensory
CONNECTIVITY OF RAT S2
relay nuclei of the thalamus. Proc R Soc Lond B Biol Sci 172:173–
185.
Jones EG, Powell TP. 1970. Connexions of the somatic sensory cortex of the rhesus monkey. 3. Thalamic connexions. Brain 93:37–
56.
Jones EG, Burton H, Porter R. 1975. Commissural and cortico-cortical ‘‘columns’’ in the somatic sensory cortex of primates. Science
190:572–574.
Jones EG, Coulter JD, Hendry SH. 1978. Intracortical connectivity
of architectonic fields in the somatic sensory, motor and parietal
cortex of monkeys. J Comp Neurol 181:291–347.
Kaas JH. 1983. What, if anything, is SI? Organization of first somatosensory area of cortex. Physiol Rev 63:206–231.
Kaas JH. 2004. Evolution of somatosensory and motor cortex in primates. Anat Rec A Discov Mol Cell Evol Biol 281:1148–1156.
Karhu J, Tesche CD. 1999. Simultaneous early processing of sensory input in human primary (SI) and secondary (SII) somatosensory cortices. J Neurophysiol 81:2017–2025.
Koralek KA, Olavarria J, Killackey HP. 1990. Areal and laminar organization of corticocortical projections in the rat somatosensory
cortex. J Comp Neurol 299:133–150.
Krubitzer LA, Kaas JH. 1987. Thalamic connections of three representations of the body surface in somatosensory cortex of gray
squirrels. J Comp Neurol 265:549–580.
Krubitzer LA, Kaas JH. 1990. The organization and connections of
somatosensory cortex in marmosets. J Neurosci 10:952–974.
Krubitzer LA, Sesma MA, Kaas JH. 1986. Microelectrode maps,
myeloarchitecture, and cortical connections of three somatotopically organized representations of the body surface in the parietal
cortex of squirrels. J Comp Neurol 250:403–430.
Krubitzer L, Manger P, Pettigrew J, Calford M. 1995. Organization
of somatosensory cortex in monotremes: in search of the prototypical plan. J Comp Neurol 351:261–306.
Kunzle H. 1978. Cortico-cortical efferents of primary motor and
somatosensory regions of the cerebral cortex in Macaca Fascicularis. Neuroscience 3:25–39.
Kwegyir-Afful EE, Keller A. 2004. Response properties of whiskerrelated neurons in rat second somatosensory cortex. J Neurophysiol 92:2083–2092.
Li XG, Florence SL, Kaas JH. 1990. Areal distributions of cortical
neurons projecting to different levels of the caudal brain stem
and spinal cord in rats. Somatosens Mot Res 7:315–335.
Lin CS, Merzenich MM, Sur M, Kaas JH. 1979. Connections of
areas 3b and 1 of the parietal somatosensory strip with the ventroposterior nucleus in the owl monkey (Aotus trivirgatus). J
Comp Neurol 185:355–371.
Manson J. 1969. The somatosensory cortical projection of single
nerve cells in the thalamus of the cat. Brain Res 12:489–492.
Manzoni T, Caminiti R, Spidalieri G, Morelli E. 1979. Anatomical
and functional aspects of the associative projections from somatic
area SI to SII. Exp Brain Res 34:453–470.
Manzoni T, Barbaresi P, Conti F. 1984. Callosal mechanism for the
interhemispheric transfer of hand somatosensory information in
the monkey. Behav Brain Res 11:155–170.
Manzoni T, Barbaresi P, Bernardi S. 1990. Matching of receptive
fields in the association projections from SI to SII of cats. J Comp
Neurol 300:331–345.
Murray GM, Zhang HQ, Kaye AN, Sinnadurai T, Campbell DH,
Rowe MJ. 1992. Parallel processing in rabbit first (SI) and second
973
(SII) somatosensory cortical areas: effects of reversible inactivation by cooling of SI on responses in SII. J Neurophysiol 68:703–
710.
Paxinos G, Watson C. 1998. The rat brain in stereotaxic coordinates. 4th ed. San Diego: Academic Press.
Pierret T, Lavallee P, Deschenes M. 2000. Parallel streams for the
relay of vibrissal information through thalamic barreloids. J Neurosci 20:7455–7462.
Pons TP, Garraghty PE, Friedman DP, Mishkin M. 1987. Physiological evidence for serial processing in somatosensory cortex. Science 237:417–420.
Pons TP, Garraghty PE, Mishkin M. 1988. Lesion-induced plasticity
in the second somatosensory cortex of adult macaques. Proc Natl
Acad Sci U S A 85:5279–5281.
Pons TP, Garraghty PE, Mishkin M. 1992. Serial and parallel processing of tactual information in somatosensory cortex of rhesus
monkeys. J Neurophysiol 68:518–527.
Qi HX, Lyon DC, Kaas JH. 2002. Cortical and thalamic connections
of the parietal ventral somatosensory area in marmoset monkeys
(Callithrix jacchus). J Comp Neurol 443:168–182.
Remple MS, Henry EC, Catania KC. 2003. Organization of somatosensory cortex in the laboratory rat (Rattus norvegicus): evidence
for two lateral areas joined at the representation of the teeth.
J Comp Neurol 467:105–118.
Rowe MJ, Sessle BJ. 1968. Somatic afferent input to posterior thalamic neurones and their axon projection to the cerebral cortex in
the cat. J Physiol 196:19–35.
Schwark HD, Esteky H, Jones EG. 1992. Corticocortical connections
of cat primary somatosensory cortex. Exp Brain Res 91:425–
434.
Spreafico R, Hayes NL, Rustioni A. 1981. Thalamic projections to
the primary and secondary somatosensory cortices in cat: single
and double retrograde tracer studies. J Comp Neurol 203:67–90.
Stevens RT, London SM, Apkarian AV. 1993. Spinothalamocortical
projections to the secondary somatosensory cortex (SII) in squirrel
monkey. Brain Res 631:241–246.
Tsai ML, Kuo CC, Sun WZ, Yen CT. 2004. Differential morphine
effects on short- and long-latency laser-evoked cortical responses
in the rat. Pain 110:665–674.
Turman AB, Morley JW, Zhang HQ, Rowe MJ. 1995. Parallel processing of tactile information in cat cerebral cortex: effect of reversible inactivation of SII on SI responses. J Neurophysiol
73:1063–1075.
Weller RE, Sur M, Kaas JH. 1987. Callosal and ipsilateral cortical
connections of the body surface representations in SI and SII of
tree shrews. Somatosens Res 5:107–133.
Wise SP, Jones EG. 1978. Developmental studies of thalamocortical
and commissural connections in the rat somatic sensory cortex.
J Comp Neurol 178:187–208.
Woolsey CN, Wang GH. 1945. Somatic sensory areas I and II of the
cerebral cortex of the rabbit. Fed Proc 4:79.
Zhang HQ, Murray GM, Coleman GT, Turman AB, Zhang SP, Rowe
MJ. 2001a. Functional characteristics of the parallel SI- and SIIprojecting neurons of the thalamic ventral posterior nucleus in
the marmoset. J Neurophysiol 85:1805–1822.
Zhang HQ, Zachariah MK, Coleman GT, Rowe MJ. 2001b. Hierarchical equivalence of somatosensory areas I and II for tactile
processing in the cerebral cortex of the marmoset monkey. J Neurophysiol 85:1823–1835.