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Neuroscience 219 (2012) 120–136
PROJECTIONS OF THE CENTRAL MEDIAL NUCLEUS OF THE
THALAMUS IN THE RAT: NODE IN CORTICAL, STRIATAL AND LIMBIC
FOREBRAIN CIRCUITRY
R. P. VERTES, a* W. B. HOOVER a AND
J. J. RODRIGUEZ b,c,d
Abstract—The central medial nucleus (CM) of thalamus is a
prominent cell group of the rostral intralaminar complex of
the thalamus. No previous report in the rat has comprehensively described the projections of CM. Using the
anterograde anatomical tracer, Phaseolus vulgaris leucoagglutinin, we examined the efferent projections of CM, comparing projections from rostral (CMr) and caudal (CMc)
regions of CM. We showed that the central medial nucleus
distributes substantially to several cortical sites and to a limited number of subcortical structures. The primary CM targets were anterior and posterior regions of cortex, the
claustrum, the caudate-putamen, the nucleus accumbens
(ACC), the olfactory tubercle, and the amygdala. CMr and
CMc distribute to several of the same structures but essentially to different parts of these structures. By comparison,
CMr more strongly targets limbic structures, CMc more heavily sensorimotor structures. Main CMr projection sites were
the medial agranular, anterior cingulate, prelimbic, dorsolateral orbital and dorsal agranular insular cortices, the dorsal
striatum, the ACC, and the basolateral nucleus of the amygdala. Main CMc cortical projection sites were the ventrolateral, lateral and dorsolateral orbital cortices, dorsal, ventral
and posterior agranular insular cortices, visceral cortex, primary somatosensory and motor cortices, and perirhinal cortex. Main CMc subcortical projection sites were the dorsal
striatum and the lateral, central, anterior cortical, and basomedial nuclei of amygdala. The largely complementary output of CMr and CMc to diverse areas of cortex and to
regions of the striatum and amygdala suggest a combined
CM influence over a widespread area of the anterior cortex
and throughout the dorsal and ventral striatum and the amygdala. CM projections to limbic and sensorimotor structures
of the rostral forebrain suggest that CM may serve to integrate affective, cognitive and sensorimotor functions for
goal-directed behavior. Ó 2012 Published by Elsevier Ltd.
on behalf of IBRO.
a
Center for Complex Systems and Brain Sciences, Florida
Atlantic University, Boca Raton, FL 33431, United States
b
IKERBASQUE, Basque Foundation for Science, 48011
Bilbao, Spain
c
Department of Neurosciences, University of the Basque Country
UPV/EHU, 48940 Leioa, Spain
d
Institute of Experimental Medicine, ASCR, Videnska 1083, 142
20 Prague, Czech Republic
*Corresponding author. Tel: +1-561-297-2362; fax: +1-561-2972363.
E-mail address: vertes@ccs.fau.edu (R. P. Vertes).
Abbreviations: AAA, anterior amygdaloid area; ac, anterior commissure; AC, anterior cingulate cortex; ACC, nucleus accumbens; AGm,
medial agranular (frontal) cortex; AGl, lateral agranular (frontal) cortex;
AH, anterior nucleus of hypothalamus; AI,d,p,v, agranular insular cortex, dorsal, posterior and ventral divisions; AM, anteromedial nucleus
of thalamus; AON, anterior olfactory nucleus; AUD, auditory cortex;
AV, anteroventral nucleus of thalamus; BLA, basolateral nucleus of
amygdala; BMA, basomedial nucleus of amygdala; BST, bed nucleus
of stria terminalis; CEA, central nucleus of amygdala; CL, central lateral
nucleus of thalamus; CLA, claustrum; CM,c,r, central medial nucleus of
thalamus, caudal division, rostral division; COA,a,p, cortical nucleus of
amygdala, anterior, posterior division; C-P, caudate-putamen, striatum;
DLO, dorsolateral orbital cortex; DM, delayed matching to sample/position task; DMh, dorsomedial nucleus of hypothalamus; DNM, delayed
non-matching to sample/position task; EC, entorhinal cortex; ECT,
ectorhinal cortex; EP, endopiriform nucleus; GP, globus pallidus; GU,
gustatory cortex; IAM, interanteromedial nucleus of thalamus; IL,
infralimbic cortex; ILt, intralaminar nuclei of thalamus; IMD, intermediodorsal nucleus of thalamus; LA, lateral nucleus of amygdala; LD,
lateral dorsal nucleus of thalamus; LH, lateral habenula; LHy, lateral
hypothalamus; LO, lateral orbital cortex; LP, lateral posterior nucleus of
thalamus; LPO, lateral preoptic area; LS, lateral septum; MA, magnocellular preoptic nucleus; MD, mediodorsal nucleus of thalamus; MO,
medial orbital cortex; mPFC, medial prefrontal cortex; MPO, medial
preoptic area; MS, medial septum; mt, mammillothalamic tract; OT,
olfactory tubercle; PB, phosphate buffer; PC, paracentral nucleus of
thalamus; PFC, prefrontal cortex; PH, posterior hypothalamus; PHA-L,
Phaseolus vulgaris-leucoagglutinin; PIR, piriform cortex; PL, prelimbic
cortex; PO, posterior nucleus of thalamus; PRC, perirhinal cortex; PT,
paratenial nucleus of thalamus; PTL, posterior parietal cortex; PV,
paraventricular nucleus of thalamus; RE, nucleus reuniens of thalamus; RF, reticular formation; RH, rhomboid nucleus of thalamus; RSC,
retrosplenial cortex; RT, reticular nucleus of thalamus; SF, septofimbrial nucleus; SI, substantia innominata; SMT, submedial nucleus of
thalamus; SSI, primary somatosensory cortex; SSII, secondary somatosensory cortex; TBS, Tris-buffered saline; TEA, temporal association area; TR, postpiriform transition area; VAL, ventral anterior-lateral
nucleus of thalamus; VB, ventral basal nucleus of thalamus; VISC,
visceral cortex; VLO, ventrolateral orbital cortex; VM, ventral medial
nucleus of thalamus; VMh, ventromedial nucleus of hypothalamus; VO,
ventral orbital cortex; ZI, zona incerta; 3V, third ventricle.
Key words: medial prefrontal cortex, insular cortex, nucleus
accumbens, striatum, basolateral nucleus of amygdala, working memory, limbic thalamus.
INTRODUCTION
The central medial nucleus (CM) is a prominent cell group
of the rostral intralaminar complex of the thalamus which
also includes the paracentral (PC) and central lateral nuclei. CM extends rostrocaudally over a considerable
length of the thalamus (Swanson, 2004).
The midline and intralaminar (ILt) nuclei receive a diverse and widespread set of afferent projections (Krout
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http://dx.doi.org/10.1016/j.neuroscience.2012.04.067
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et al., 2002; Van der Werf et al., 2002; Vertes, 2002;
McKenna and Vertes, 2004). Specifically, CM receives a
relatively vast array of projections, primarily from the brainstem and caudal diencephalon. Significant among them
are afferents from the brainstem reticular formation (RF).
Several early reports in the rat demonstrated that the intralaminar nuclei, together with the zona incerta, were the major forebrain targets of RF projections (Jones and Yang,
1985; Vertes et al., 1986; Vertes and Martin, 1988). These
connections constitute a principal component of the
ascending RF activating system – or a reticular-ILt-cortical
circuit responsible for behavioral and cortical EEG arousal
of waking and REM sleep (Steriade and Glenn, 1982;
Glenn and Steriade, 1982; Steriade et al., 1982; Kinomura
et al., 1996). Damage to this system profoundly alters
states of consciousness (Castaigne et al., 1981; Mair,
1994; Schiff, 2008), leading to the view that the midline/
ILt thalamus (including CM) is critically involved in processes of arousal and attention (Paus, 2000; Van der Werf
et al., 2002; Schiff, 2008).
Whereas CM receives widespread afferents, the output
of CM is relatively restricted and mainly directed to rostral
regions of the cortex, or to the orbitomedial prefrontal cortex (PFC) (Berendse and Groenewegen, 1991; Van der
Werf et al., 2002). This suggests a role for CM in PFC functions such as decision-making and goal-directed behaviors
(Dalley et al., 2004; Kolb et al., 2004; Sul et al., 2010).
Specifically, CM/ILt lesions have been shown to produce impairments in working memory as assessed by
delayed matching (DM) and non-matching (DNM) to
sample/position tasks in rats (Burk and Mair, 1998; Mair
et al., 1998; Bailey and Mair, 2005; Newman and Burk,
2005; Mitchell and Dalrymple-Alford, 2005, 2006; Mair
and Hembrook, 2008). For instance, Mair and Hembrook
(2008) demonstrated that pharmacologically or electrically elicited activation of ILt improved performance on a
DM to position task, while ILt suppression impaired performance on the task.
On the human level, Van der Werf et al. (1999) described severe impairments in declarative memory in a
patient with damage to the right side of the intralaminar
thalamus which were attributed to ‘‘impaired use of mental
flexibility’’. They postulated that this dysfunction ‘‘arose
from the loss of cortical activation, caused by deafferentation of the prefrontal cortex through damage to the intralaminar nuclei’’ (Van der Werf et al., 2003).
The foregoing indicates, then, a critical role for CM in
arousal/attention and cognition and hence the need to
understand the pattern of CM projections. While earlier
reports in rats have described CM projections to some
structures (Berendse and Groenewegen, 1990, 1991;
Van der Werf et al., 2002), no previous study has comprehensively examined the output of CM. The present report,
then, sought to fully describe the pattern of CM projections throughout the brain.
EXPERIMENTAL PROCEDURES
Single injections of Phaseolus vulgaris-leuccoagglutinin (PHA-L)
were made into the rostral central medial (CMr) or caudal central
medial (CMc) nucleus of the intralaminar thalamus in 42 male
Sprague–Dawley rats (Harlan, Indianapolis, IN) weighing 300–
420 g. The experiments were approved by the Florida Atlantic
University IACUC committee and conform to all Federal regulations and National Institutes of Health Guidelines for the care
and use of laboratory animals.
PHA-L procedures
Powdered lectin from PHA-L was reconstituted to 4–5% in 0.05 M
sodium phosphate buffer (PB), pH 7.4. The PHA-L solution was
iontophoretically deposited in the brains of anesthetized rats by
means of a glass micropipette with an outside tip diameter of
40–50 lm. Rats were anesthetized for surgery using an 80 mg/
kg dose of Ketamine (100 mg/ml) and 10 mg/kg dose of Xylazine
(20 mg/ml). Positive direct current (7–12 lA) was applied through
a Grass stimulator (Model 88) coupled with a high-voltage stimulator (Frederick Haer Co., Bowdoin ME) at 2-s ‘‘on’’/2-s ‘‘off’’ intervals for 40–50 min. After a survival time of 7–10 days, rats were
deeply anesthetized with Ketamine/Xylazine (150 mg/kg and
50 mg/kg, respectively), and perfused transcardially with a heparinized buffered saline wash (50–75 ml/animal) followed by a fixative (4% paraformaldehyde, 0.2–0.5% glutaraldehyde in 0.1 M
PB, pH 7.4) (300–500 ml/animal). The brains were removed
and postfixed overnight in 4% paraformaldehyde 0.1 M PB at
4 °C, pH 7.4. Following postfixing, the brains were transferred
to 30% sucrose in 0.1 M PB solution for 2 days at 4 °C. Following
sucrose cryoprotection, 50-lm frozen sections were collected in
phosphate-buffered saline (PBS, 0.9% sodium chloride in 0.01 M
sodium phosphate buffer, pH 7.4) using a freezing microtome.
Six series of sections were taken. A complete series of sections
was treated with 1% sodium borohydride in 0.1 M PB for 30 min
to remove excess reactive aldehydes. Following this, sections
were thoroughly rinsed in 0.1 M PB, and then incubated for
60 min at room temperature in 0.5% bovine serum albumin in
Tris-buffered saline (TBS) to minimize nonspecific labeling. The
sections were then incubated in the primary antiserum directed
against PHA-L [biotinylated goat (IgG) anti-PHA-L, Vector Labs,
Burlingame, CA] and diluent (0.1% bovine serum albumin in
TBS containing 0.25% Triton X-100) at a concentration 1:500
overnight. Sections were then washed in 0.1 M PB (6 4 min)
and placed in a 1:500 concentration of biotinylated rabbit antigoat immunoglobulin (IgG) and diluent for 2 h. Sections were
washed and then incubated in a 1:100 concentration of peroxidase–avidin complex from the Elite kit (Vector Labs) and diluent
for 1 hour. Following another 0.1 M PB wash, the peroxidase
reaction product was visualized by incubation in a solution containing 0.022% 3,30 diaminobenzidine (DAB, Aldrich, Milwaukee,
WI) and 0.003% H2O2 in TBS for 6 min. Sections were then
rinsed again in 0.1 M PB (3 1 min) and mounted onto
chrome–alum gelatin-coated slides. An adjacent series of sections from each rat was stained with cresyl violet for anatomical
reference. Sections were examined using light and darkfield
optics. Injection sites, cells and labeled fibers were plotted on
representative schematic coronal sections through the brain
using sections adapted from the rat atlas of Swanson (2004).
Brightfield and darkfield photomicrographs of injection sites and
labeled fibers were taken with a QImaging (Q ICAM) camera
mounted on a Nikon Eclipse E600 microscope. Digital images
were captured and reconstructed using Nikon Elements 3.0
imaging software (Melville, NY), and adjusted for brightness
and contrast using Adobe PhotoShop 7.0 (Mountain View, CA).
Sections that were reacted without either the primary or secondary antibodies did not show immunoreactivity (data not shown).
RESULTS
The patterns of distribution of labeled fibers throughout
the brain following PHA-L injections in the rostral (CMr)
and the caudal (CMc) central medial nucleus of the rostral
ILt are described. Fig. 1 depicts the sites of injection in
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CMr (Fig. 1A, B) and CMc (Fig. 1C, D) for the schematically illustrated cases (cases 38 and 32). The patterns
of labeling obtained with these cases are representative
of those observed with non-illustrated cases.
Central medial nucleus, rostral part (CMr) (case 38)
Fig. 2 depicts the pattern of distribution of labeled fibers
throughout the brain following a PHA-L injection in the rostral part of CM (Fig. 1A, B and Fig. 2P). Labeled fibers
coursed forward from the site of injection (Fig. 2P) to
the anterior forebrain, spreading widely over the cortex
(Fig. 2A–D). Labeled axons stretched mediolaterally
across the prefrontal cortex most densely concentrated:
(1) dorsally/dorsomedially in the medial agranular
(AGm) (secondary motor) and the prelimbic (PL) cortices,
rostrally (Fig. 2A, B), and in AGm and the anterior cingulate cortex (AC) caudally (Fig. 2C, D); and (2) ventrolaterally in the dorsolateral orbital cortex (DLO), rostrally
(Fig. 2A, B) and in the dorsal agranular insular cortex
(AId), caudally (Fig. 2C, D). Of these sites, labeling was
heaviest in AC and AId (Fig. 2A–D). Some labeled fibers
were also present in the lateral agranular cortex (AGl) (primary motor) and in medial orbital cortex (MO), ventral to
PL (Fig. 2A–D). There was an absence of labeling in
olfactory structures: anterior olfactory nucleus, tenia tecta
and anterior piriform cortex (Fig. 2A–D).
Further caudally in the anterior forebrain (Fig. 2E–G),
labeled fibers of the cortex were largely restricted to AGm
and AC, dorsomedially, and to AId, ventrolaterally.
Labeled axons spread to all layers of AGm and AC, most
densely concentrated in layers 1, 3 and 6 (Fig. 2E, F).
Additional moderate to heavily labeled sites were the
nucleus accumbens (ACC), olfactory tubercle (OT),
claustrum (CLA), and rostral pole of the dorsal striatum
(or caudate-putamen, C-P) (Fig. 2E–G). These patterns
of labeling (Fig. 2A–G) are depicted in the micrographs
of Fig. 3A–C. As shown, there were three main clusters
of fibers: dorsomedially in AGm and AC; laterally in AId
and CLA; and ventromedially in ACC and OT with extensions dorsally into C-P. The anterior, core, and shell
regions of ACC bordering the anterior commissure were
densely labeled (Fig. 3B, C). Light to moderate numbers
of labeled axons were also seen in the infralimbic (IL)
and PL cortices, mainly confined to deep layers
(Fig. 2E, F).
Caudally within the anterior forebrain (septal levels)
(Fig. 2H–M), labeled fibers spread heavily throughout
the dorsal striatum, mainly localized to central regions of
C-P, rostrally (Fig. 2H–J) and to dorsomedial aspects of
C-P, caudally (Fig. 2K–M). Fig. 4 depicts a dense column
of labeled fibers stretching dorsoventrally over the central
C-P, rostrally (Fig. 4A, B), and occupying most of the dorsal/dorsomedial sector of C-P, caudally (Fig. 4C, D).
While labeled fibers continued to be present in the core
of ACC and some in the shell (Fig. 2H–J,), their numbers
declined from those of rostral levels. Outside of the dorsal
and ventral striatum, light to moderate numbers of labeled
Fig. 1. Low (A, C) and high (B, D) magnification bright-field photomicrographs of transverse sections through diencephalon showing locations of
PHA-L injections in the rostral (A, B) and caudal (C, D) central medial (CM) nucleus of the thalamus. Scale bar for A = 1100 lm; for B = 350 lm;
for C = 1150 lm; for D = 375 lm. See list for abbreviations.
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Fig. 2. Schematic depiction of labeling present in representative sections through the forebrain (A–S) produced by a PHA-L injection (red dots in P)
in the rostral part of the central medial nucleus of thalamus (case 38). Sections modified from the rat atlas of Swanson (2004). See list for
abbreviations. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Fig. 2 (continued)
axons were observed in AGm, AId, CLA and OT. At best
minor labeling was present throughout remaining regions
of the basal forebrain including the medial and lateral preoptic areas (Fig. 2J–M).
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Fig. 2 (continued)
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At the rostral diencephalon (Fig. 2N–P), labeled axons
were virtually confined to C-P and to the basolateral
nucleus (BLA) of the amygdala. As observed rostrally
(Fig. 2K–M), labeled fibers of the striatum were localized
to the dorsal half of C-P, bordering the lateral ventricle
(Fig. 2N–P). The rostro-caudal extent of BLA was heavily
labeled; few fibers were present within other parts of the
amygdala (Fig. 2N–S). This is exemplified in Fig. 5 showing dense concentrations of labeled axons rostrally
(Fig. 5A) and caudally (Fig. 5B) in BLA. Labeling was light
outside C-P and BLA, mainly localized to AGm and to the
retrosplenial cortex (RSC), dorsomedially (Fig. 2N–R),
and to areas bordering the rhinal fissure, ventrolaterally.
The latter included the posterior agranular insular cortex
(AIp) (Fig. 2N, O) and the perirhinal cortex (PRC)
(Fig. 2P–S).
At middle to caudal levels of the diencephalon
(Fig. 2Q–S), labeling weakened significantly and was
essentially restricted to caudal BLA and to parts of the cortex. As rostrally, labeled fibers spread quite heavily
throughout BLA, and the relatively few present in the cortex were primarily localized to RSC and perirhinal cortices.
Central medial nucleus, caudal part (CMc) (case 32)
Fig. 3. Low-power bright-field photomicrographs of three rostrocaudally aligned (A–C) transverse sections through the rostral forebrain
showing patterns of labeling produced by a PHA-L injection in the
rostral part of the central medial nucleus. Note the dense labeling: (a)
in the medial prefrontal cortex (mPFC) predominantly localized to the
medial agranular and anterior cortices (A–C) with some extension
ventrally into the prelimbic cortex (A); (b) in the dorsal agranular
insular cortex (A–C); (c) in the dorsal striatum (C); and (d) in the
nucleus accumbens and the ventrally adjacent OT (B,C). Scale bar
for A = 950 lm; for B = 975 lm; for C = 1120 lm. See list for
abbreviations.
Fig. 6 depicts the pattern of distribution of labeled fibers
throughout the brain following a PHA-L injection in the
caudal part of CM (Fig. 1C, D and Fig. 6Q, R). As shown,
labeled fibers exiting from the site of injection (Fig. 6Q, R)
coursed rostrally to the anterior forebrain mainly destined
for lateral regions of the cortex (Fig. 6A–D). At the rostral
pole of the cortex (Fig. 6A), labeled axons stretched mediolaterally across the cortex primarily localized to the prelimbic cortex (PL), medially and to parts of the orbital
and motor (AGl) cortices, laterally. As depicted schematically (Fig. 6A) and in the micrograph of Fig. 7A, a relatively narrow band of labeled fibers extended laterally
from the midline through all layers of PL, continued
through deep layers of the ventrolateral (VLO), lateral
(LO) and dorsolateral (DLO) orbital cortices, and ended
laterally in superficial layers of LO and DLO. Labeling
was dense in layers 1 and 3 of DLO. In addition, moderate
numbers of labeled fibers were present in AGl, but very
few in AGm.
Further caudally in the anterior PFC (Fig. 6B–D),
labeling was predominantly confined to middle to lateral
parts of the cortex, with modest labeling of the medial prefrontal cortex (mPFC), including the IL, PL and AC cortices. As shown, a dense collection of dorsomedially to
ventrolaterally oriented fibers occupied the lateral twothirds of the PFC (Fig. 6B–D), localized medially to deep
layers of VLO, LO and AGl and to CLA, and laterally to
AId and to the dorsally adjacent gustatory (GU) and primary somatosensory (SSI) cortices. These patterns are
depicted in the micrographs of Fig. 7B, C showing heavy
labeling of layers 1 and 3 of AId (Fig. 7B, C) and moderate
labeling of the CLA (Fig. 7C).
Labeled fibers were also largely restricted to lateral
parts of the cortex caudally in the anterior forebrain
(Fig. 6E–G). As depicted, labeled axons lined the lateral
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Fig. 4. Low-power bright-field photomicrographs of four rostrocaudally aligned (A–D) transverse sections through the rostral forebrain showing
patterns of labeling in the dorsal striatum (C-P) produced by a PHA-L injection in the rostral part of the central medial nucleus. Note the very dense
labeling spread throughout C-P, concentrated rostrally (A,B) dorsoventrally throughout the mid-central C-P, and caudally (C,D) within the medial/
dorsomedial half of C-P. Scale bar for A = 975 lm; for B, C = 1000 lm; for D = 950 lm. See list for abbreviations.
edge of the corpus callosum (anterior forceps) (Fig. 6E,F)
and extended from there to ventrolateral regions of cortex, heavily concentrated in superficial layers (1 and 3)
of AId and GU and less so dorsally in SSI. Additional moderately labeled sites were the CLA (Fig. 6E–G) and AGl
(Fig. 6E, F). Few labeled fibers were present in mPFC
or within anterior regions of C-P, ACC and OT.
Labeling further caudally in the forebrain (septal levels) (Fig. 6H–K) was restricted to a few sites, the most
prominent being ventral/ventromedial parts of the dorsal
striatum. As shown schematically (Fig. 6H–K) and in the
micrographs of Fig. 7D, E dense aggregates of labeled
axons were present rostrocaudally throughout the ventral
C-P, lateral/dorsolateral to ACC, rostrally (Fig. 7D), and
on the lateral border of the globus pallidus (GP), caudally
(Fig. 7E). Relatively significant numbers of fibers were
also present along the lateral convexity of the cortex
extending continuously from AC to regions bordering the
rhinal fissure, including AId and GU, rostrally (Fig. 6H)
and AIp, caudally (Fig. 6I–K). Of these sites, labeling
was fairly pronounced in AId, GU and AIp, but less dense
in AGl and the somatosensory cortices (SSI and SSII).
Additional light to moderately labeled sites were CLA,
ACC, OT, and the substantia innominata (SI) (Fig. 6H–K).
At the rostral diencephalon (Fig. 6L–Q), labeled axons
were virtually confined to the ventrolateral quadrant of the
brain: within C-P, AIp, PRC, and the amygdala. Few fibers
were visible throughout remaining regions of the cortex or
within the thalamus and hypothalamus. The labeled
axons of the thalamus largely represented fibers exiting
the thalamus from the site of injection (Fig. 6Q, R). As rostrally, labeled fibers of the striatum were mainly found
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Fig. 5. (A, B) Darkfield photomicrographs of transverse sections through the rostral (A) and caudal (B) amygdala showing patterns of labeling
produced by a PHA-L injection in the rostral part of the central medial nucleus. Note dense labeling restricted to the basal lateral nucleus of
amygdala. C–E: Darkfield photomicrographs of three rostral to caudal transverse sections (C–E) through the amygdala showing patterns of labeling
produced by a PHA-L injection in the caudal part of the central medial nucleus. Note pronounced labeling in the central, lateral and basolateral nuclei
of amygdala. Scale bar for A = 330 lm; for B = 310 lm; for C–E = 500 lm. See list for abbreviations.
ventromedially in C-P, bordering GP (Fig. 6L, M), with few
extending to caudal aspects of C-P (Fig. 6N–R). Striatal
labeling was very dense in a region dorsal to the anterior
nuclei of the amygdala (Fig. 6L). Of the areas around the
rhinal fissure, labeling was heaviest in AIp (particularly
layers 3 and 5/6), in visceral cortex (VISC) (Fig. 6L, M)
and in the PRC (Fig. 6O–R), and much less pronounced
in the ectorhinal (ECT) and piriform cortices (Fig. 6O–
Q). Unlike rostral CM injections (see above) wherein
amygdala labeling was virtually confined to the basolateral nucleus of amygdala, caudal CM injections gave rise
to labeling of several nuclei of the amygdala (Fig. 5C–E).
As depicted (Fig. 5L–P), these included parts of the anterior (AAA), central (CEA), medial, anterior cortical
(COAa), lateral (LA), basolateral and basomedial (BMA)
nuclei of amygdala. Labeling was densest in LA
(Fig. 5C, D), lateral aspects of BLA, BMA and the capsular region of CEA (Fig. 5D, E).
The pattern of labeling caudally in the diencephalon
(Fig. 6Q–S) was similar to that seen rostrally; that is,
essentially confined to PRC and to the amygdala. Labeled
fibers spread to all layers of PRC but were most densely
concentrated in inner layers. A few fibers extended
ventrally from PRC to the entorhinal cortex. At the caudal
amygdala, BLA was moderately labeled and the postpiriform area lightly labeled (Fig. 6R, S).
DISCUSSION
Using an anterograde tracing technique, we examined the
efferent projections of the central medial nucleus of the
intralaminar thalamus in the rat. CM predominantly targets
the prefrontal/frontal cortex, the dorsal and ventral striatum
and the amygdala, distributing heavily to these sites
(Fig. 8). Rostral and caudal CM project commonly to several structures, but to different regions of these structures.
In effect, there is relatively little overlap in the two sets of
projections (CMr and CMc) (Fig. 8). CM output to limbic
and sensorimotor structures of the rostral forebrain
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Fig. 6. Schematic depiction of labeling present in representative sections through the forebrain (A–S) produced by a PHA-L injection (red dots in Q,
R) in the caudal part of the central medial nucleus of thalamus (case 32). Sections modified from the rat atlas of Swanson (2004). See list for
abbreviations. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
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Fig. 6 (continued)
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Fig. 6 (continued)
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Fig. 7. (A–C) Low-power bright-field photomicrographs of three rostrocaudally aligned transverse sections through the rostral forebrain showing
patterns of labeling produced by a PHA-L injection in the caudal part of the central medial nucleus. Note the dense labeling ventrolaterally within the
anterior cortex, localized to the DLO, rostrally (A) and to the dorsal agranular insular cortex, caudally (B, C), mainly concentrated in layers 1 and 3 of
these cortical regions. Note also pronounced labeling in the prelimbic cortex (A) and the anterior claustrum (C). (D, E) Low-power bright-field
photomicrographs of a rostral (D) and caudal (E) transverse sections through the forebrain showing patterns of labeling in the dorsal striatum
produced by a PHA-L injection in the caudal part of the central medial nucleus. Note dense aggregates of labeled fibers ventrally/ventrolaterally in CP, rostrally (D) and medially along the lateral border of the globus pallidus, caudally (E). Note also pronounced labeling in the posterior agranular
insular and visceral cortices (E). Scale bar for A, D = 500 lm; for B = 310 lm; for C = 750 lm; for E = 400 lm. See list for abbreviations.
suggests that CM may serve to integrate affective, cognitive and sensorimotor functions for goal-directed behavior.
A note on potential uptake by fibers of passage
With all anterograde tracers, there is the possibility of
uptake of tracers not only by cells at the site of injection
but also by fibers passing through the injection – the fibers
of passage problem. This is particularly relevant here
since the intralaminar nuclei are embedded in the fibers
of the internal medullary lamina. Of the anterograde tracers, however, PHA-L appears to be the least susceptible
to uptake by coursing fibers (Gerfen and Sawchenko,
1984; Groenewegen and Wouterlood, 1990). Specifically,
PHA-L requires ionotophoretic application and is only successfully transported by cells that have incorporated the
tracer, that is, not by cells/fibers in the zone of passive
spread of the tracer (Gerfen and Sawchenko, 1984). In
this regard, we saw no evidence of transport from regions
adjacent to CM which were sometimes included in the
area of passive spread of the tracer such as the intermediodorsal (IMD), paracentral or rhomboid nuclei. On rare
occasions we have observed the retrograde transport of
PHA-L (suggesting some uptake by passing fibers), but
this generally only occurs with large PHA-L injections
and was not presently seen. In addition, previous studies
using PHA-L have described distinct and largely nonoverlapping midline/ILt thalamic projections to the striatum and cortex (Berendse and Groenewegen, 1990,
1991), despite the fact that injection sites for some cell
groups are traversed by fibers from other ILt nuclei en
route to their targets (Berendse and Groenewegen,
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R. P. Vertes et al. / Neuroscience 219 (2012) 120–136
Cortex
CMr
medial
AC
AGm
PL
IL
RSC
lateral
AGl
LO
VLO
DLO
AId
AIp
GU
SSI
SSII
PRC
ECT
EC
Fiber Density
light
moderate
heavy
CMc
Basal Forebrain
ACC
CLA
C-P
OT
Amygdala
AAA
BLA
BMA
LA
CEA
COAa
Fig. 8. Summary diagram of the pattern of projections of the rostral
(CMr) and the caudal (CMc) central medial nucleus of the thalamus to
its main targets; namely, the cerebral cortex (medial and lateral
regions), the basal forebrain and the amygdala. The relative density
of projections to each structure is indicated by the thickness of the
lines. See list for abbreviations.
1990). Accordingly, the uptake of PHA-L by fibers coursing through CM was likely minimal.
Overview of CM projections
CMr projections. The main CMr targets were rostral
regions of the cortex, the CLA, dorsal striatum, ACC,
OT, and BLA. Some secondary sites were the posterior
insular and perirhinal cortices. With respect to the cortex,
CMr distributes to rostral but essentially not to caudal
regions of the cortex, densely innervating the AGm,
anterior cingulate, prelimbic, DLO and AId cortices. CMr
projects much more heavily to the dorsal (AGm and AC)
than to the ventral mPFC (PL and IL). CMr distributes
massively throughout rostrocaudal extent of the dorsal
striatum, mainly targeting central regions of C-P, rostrally,
and the dorsal/dorsomedial half of C-P, caudally. Within
the ventral striatum, CMr fibers were virtually confined
to the anterior ACC, terminating substantially in the rostral
pole, core and shell regions of the rostral ACC. Finally,
CMr fibers distribute throughout the basolateral nucleus
of the amygdala, virtually blanketing BLA. With the exception of lateral half of the rostral pole of BLA, the entire nucleus was densely labeled.
CMc projections. Major CMc termination sites were
lateral regions of the anterior cortex, the CLA, the dorsal
133
striatum, the posterior agranular insular cortex, the PRC
and the amygdala. CMc fibers generally avoided the
mPFC, distributing substantially instead to lateral parts
of the prefrontal cortex including the ventrolateral, lateral
and dorsolateral orbital cortices, the dorsal (AId) and ventral agranular insular cortices, gustatory/VISC cortex, and
the primary somatosensory (SSI) and motor (AGl) cortices. Of these regions, AId, gustatory and SSI cortices
were densely labeled; AGl was slightly less heavily
labeled. At caudal levels of the cortex, CMc fibers were
mainly localized to regions bordering (and dorsal to) the
rhinal fissure including the posterior agranular insular,
PRC, and visceral cortices.
CMc distributes heavily to the dorsal striatum, with
fibers predominately targeting the ventral/ventrolateral
quadrant of C-P, rostrally, and the dorsoventral expanse
of the medial C-P, caudally. CMc projects sparsely to
the rostral C-P. CMc fibers distribute widely throughout
the amygdala reaching most subnuclei. These include
regions of the anterior, lateral (LA), central (CEA), medial,
cortical and basal (BLA and BMA) nuclei of amygdala,
with most pronounced projections to LA, capsular CEA,
anterior cortical, and BMA.
Major CM projections: comparisons with previous
studies
Projections to the cortex. As described, CMr and CMc
distribute to essentially non-overlapping regions of the
cortex. In a review, Van der Werf et al. (2002) described
similar findings, stating: ‘‘There is a striking difference in
the pattern of terminal labeling following rostral or caudal
injections in the CeM. At cortical levels, virtually no overlap can be seen between the termination fields resulting
from either rostral or caudal injections.’’
CMr projections to cortex. We showed that CMr projections to the cortex were virtually restricted to anterior
regions of the cortex. In an early examination of midline/
ILt thalamic projections to cortex in rats, Berendse and
Groenewegen (1991) similarly reported that the rostral
CM targets the anterior PFC, but unlike present findings,
described more limited CMr projections to the cortex, or
mainly confined to AC and to anterior PL. Few fibers were
identified in AGm and virtually none in DLO or AId. Differences may involve differing locations of injections in CMr.
Supporting present findings of a pronounced CMr input to
AGm, Reep and Corwin (1999) described substantial
numbers of labeled cells in rostral CMr following retrograde injections in the rostral AGm of rats. In like manner,
we previously showed that retrograde injections in the
dorsal mPFC (AGm and AC) of rats produced robust cell
labeling in CM, predominantly localized to CMr, whereas
those in the ventral mPFC (PL and IL) gave rise to few
labeled neurons in CM (Hoover and Vertes, 2007).
CMc projections to cortex. As described, CMc distributes heavily to lateral regions of the cortex – around and
dorsal to the rhinal fissure. An early report by Reep and
Winans in rats (1982) described labeled cells in CM
(mainly in CMc) with retrograde injections in AId, but
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R. P. Vertes et al. / Neuroscience 219 (2012) 120–136
few with injections in AIv. Jasmin et al. (2004) subsequently demonstrated pronounced cell labeling in CM,
mainly restricted to CMc, following injections in the rostral
agranular insular cortex (AId + AIv) of rats. Finally,
Guldin and Markowitsch (1983) reported that injections
of retrograde tracers in the PRC give rise to labeled cells
confined to the midline/ILt thalamus, mainly to CMc.
Projections to the dorsal striatum (caudate-putamen)
We showed that CMr and CMc distribute massively to the
dorsal striatum and to largely separate regions of C-P. An
early examination of thalamic afferents to the striatum
(Berendse and Groenewegen, 1990) described a similar
pattern of CMr projections to C-P in rats, but less widely
distributed throughout the striatum than shown here – or
as we demonstrated (Fig. 2) to most of the medial/central
C-P, rostrally, and throughout the dorsal half of C-P,
caudally.
In partial support of the present findings, Van der Werf
et al. (2002) demonstrated that CMc fibers target the ventrolateral quadrant C-P – or the fundus of the striatum.
Unlike their findings, however, we showed that CMc fibers
are not confined to the fundus but spread throughout the
ventrolateral C-P, densely concentrated along the lateral
border of GP. Finally, retrograde tracer injections in C-P
gave rise to labeled cells in several midline/ILt nuclei in
rats including CM, with the strongest CM labeling with
injections in the dorso-central and ventrolateral C-P (Erro
et al., 2002).
Projections to the ventral striatum (nucleus
accumbens)
We showed that: (1) CMr but not CMc projects to ACC; and
(2) CMr distributes heavily to the rostral pole and core of
ACC, and moderately to lateral parts of the medial shell
of ACC. Several previous reports in rats have shown that
the midline/ILt thalamus is a major source of projections
to ACC, mainly originating from the paraventricular (PV),
paratenial (PT), IMD, and CM nuclei (Groenewegen
et al., 1980; Phillipson and Griffiths, 1985; Berendse
et al., 1988; Berendse and Groenewegen, 1990; Su and
Bentivoglio, 1990; Brog et al., 1993; Van der Werf et al.,
2002; Li and Kirouac, 2008; Vertes and Hoover, 2008).
Consistent with present findings, Berendse and
Groenewegen (1990) demonstrated that retrograde injections in the core but not the shell of ACC gave rise to robust
labeling in CM and that anterograde injections in CMr produced strong terminal labeling in the rostral core of ACC. In
accord with this, Brog et al. (1993) described a progressive
decrease in numbers of labeled cells in CM with retrograde
injections in the core, lateral shell and medial shell of ACC.
afferents to the amygdala from several nuclei of thalamus,
mainly those of the midline/ILt thalamus. Of the latter, projections were heaviest from the PV, PT, interanteromedial
and parafascicular nuclei to the amygdala, mainly to BLA.
CM projections to the amygdala were modest. By contrast, Su and Bentivoglio (1990) demonstrated moderately
retrograde cell labeling in CM following large amygdaloid
injections centered in BLA in rats; while Turner and
Herkenham (1991) described dense CM projections to
the amygdala selectively targeting BLA – and heavier to
the anterior than to the posterior BLA.
Central medial nucleus: an integral component of a
midline thalamic network with widespread influence
on the limbic forebrain
Although CM is part of the rostral ILt (Van der Werf et al.,
2002), it lies on the midline and as such appears to share
characteristics with the midline thalamic nuclei. As a
group, the midline thalamic nuclei (and CM) receive a diverse and widespread set of afferent projections and predominately target limbic forebrain structures (Van der
Werf et al., 2002; Vertes, 2006). Accordingly, the midline
nuclei appear to represent an important interface between
‘lower’ and ‘higher’ levels of the limbic system in affective
and cognitive control (Vertes, 2006). Although partially
overlapping, each of the midline thalamic nuclei projects
to unique sets of limbic forebrain structures. For instance,
the reuniens and rhomboid nuclei of the ventral midline
thalamus primarily target limbic cortical structures, prominently including the hippocampus and mPFC (Herkenham 1978; Wouterlood et al., 1990; Wouterlood, 1991;
Dollerman-Van der Weel and Witter, 1996; Risold et al.,
1997; Bokor et al., 2002; Vertes, 2006; Vertes et al.,
2006), whereas the paraventricular and paratenial nuclei
of the dorsal midline thalamus mainly distribute to limbic
subcortical sites in rats and primates (Li and Kirouac,
2008; Vertes and Hoover, 2008; Hsu and Price, 2009).
By comparison, the central medial nucleus (lying between
the dorsal and ventral midline groups) projects more
uniformly to subcortical and cortical limbic sites. In this
respect, CM may bridge the dorsal and ventral midline
thalamus, simultaneously influencing subcortical and cortical structures. Finally, unlike other midline nuclei, CM is
a major source of afferents to the dorsal striatum suggesting that CM integrates sensorimotor and limbic functions.
In summary, CM appears ideally positioned to integrate the activity of its main targets, the prefrontal cortex,
the dorsal and ventral striatum and the amygdala, for
goal-directed behavior. In effect, CM may promote the
temporary storage of information (working memory) at
the PFC, its evaluation at the amygdala and nucleus
accumbens, and preparation for actions at the striatum.
Projections to the amygdala
We showed that CMr virtually exclusively targets BLA of
amygdala, whereas CMc fibers distribute throughout the
amygdala terminating in the lateral, central, anterior cortical and basomedial nuclei of amygdala.
In an early examination of thalamo-amygdaloid projections in the rat, Ottersen and Ben-Ari (1979) described
Acknowledgements—The present study was supported by NSF
grant IOS 0820639 to RPV and by the Government of the Basque
Country grant (AE-2010-1-28; AEGV10/16) and the grant agency
of the Czech Republic (GACR 309/09/1696) to JJR. The authors
sincerely thank two anonymous reviewers for their very constructive comments on earlier versions of the manuscript.
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R. P. Vertes et al. / Neuroscience 219 (2012) 120–136
REFERENCES
Bailey KR, Mair RG (2005) Lesions of specific and nonspecific
thalamic nuclei affect prefrontal cortex-dependent aspects of
spatial working memory. Behav Neurosci 119:410–419.
Berendse HW, Groenewegen HJ (1990) Organization of the
thalamostriatal projections in the rat, with special emphasis on
the ventral striatum. J Comp Neurol 299:187–228.
Berendse HW, Groenewegen HJ (1991) Restricted cortical
termination fields of the midline and intralaminar thalamic nuclei
in the rat. Neuroscience 42:73–102.
Berendse HW, Voorn P, te Kortschot A, Groenewegen HJ (1988)
Nuclear origin of thalamic afferents of the ventral striatum
determines their relation to patch/matrix configurations in
enkephalin immunoreactivity in the rat. J Chem Neuroanat
1(3):10.
Bokor H, Csáki A, Kocsis K, Kiss J (2002) Cellular architecture of the
nucleus reuniens thalami and its putative aspartatergic/
glutamatergic projection to the hippocampus and medial septum
in the rat. Eur J Neurosci 16:1227–1239.
Brog JS, Salyapongse A, Deutch AY, Zahm DS (1993) The patterns
of afferent innervation of the core and shell in the ‘‘accumbens’’
part of the rat ventral striatum: immunohistochemical detection of
retrogradely
transported
fluoro-gold.
J
Comp
Neurol
338:255–278.
Burk JA, Mair RG (1998) Thalamic amnesia reconsidered: excitotoxic
lesions of the intralaminar nuclei, but not the mediodorsal nucleus,
disrupt place delayed matching-to-sample performance in rats
(Rattus norvegicus). Behav Neurosci 112:54–67.
Castaigne P, Lhermitte F, Buge A, Escourolle R, Hauw JJ, LyonCaen O (1981) Paramedian thalamic and midbrain infarct: clinical
and neuropathological study. Ann Neurol 10:127–148.
Dalley JW, Cardinal RN, Robbins TW (2004) Prefrontal executive and
cognitive functions in rodents: neural and neurochemical
substrates. Neurosci Biobehav Rev 28:771–784.
Dollerman-Van der Weel MJ, Witter MP (1996) Projections from
nucleus reuniens thalami to the entorhinal cortex, hippocampal
field CA1, and the subiculum in the rat arise from different
populations of neurons. J Comp Neurol 364:637–650.
Erro ME, Lanciego JL, Gimenez-Amaya JM (2002) Re-examination of
the thalamostriatal projections in the rat with retrograde tracers.
Neurosci Res 42:45–55.
Gerfen CR, Sawchenko PE (1984) An anterograde neuroanatomical
tracing method that shows the detailed morphology of neurons,
their axons and terminals: immunohistochemical localization of an
axonally transported plant lectin, Phaseolus vulgaris
leucoagglutinin (PHA-L). Brain Res 290:219–238.
Glenn LL, Steriade M (1982) Discharge rate and excitability of
cortically projecting intralaminar thalamic neurons during waking
and sleep states. J Neurosci 2:1387–1404.
Groenewegen HJ, Wouterlood FG (1990) Light and electron
microscopic tracing of neuronal connections with Phaseolus
vulgaris-leucoagglutinin (PHA-L), and combinations with other
neuroanatomical techniques. In: Handbook of chemical
neuroanatomy, vol. 8: Analysis of neuronal microcircuits and
synaptic interactions (Bjorklund A, Hokfelt T, Wouterlood FG,
VandenPol A, eds), pp 47–124. Amsterdam: Elsevier.
Groenewegen HJ, Becker NE, Lohman AH (1980) Subcortical
afferents of the nucleus accumbens septi in the cat, studied with
retrograde axonal transport of horseradish peroxidase and
bisbenzimid. Neuroscience 5:1903–1916.
Guldin WO, Markowitsch HJ (1983) Cortical and thalamic afferent
connections of the insular and adjacent cortex of the rat. J Comp
Neurol 215:135–153.
Herkenham M (1978) The connections of the nucleus reuniens
thalami: evidence for a direct thalamo-hippocampal pathway in
the rat. J Comp Neurol 177:589–610.
Hoover WB, Vertes RP (2007) Anatomical analysis of afferent
projections to the medial prefrontal cortex in the rat. Brain Struct
Funct 212:149–179.
135
Hsu DT, Price JL (2009) Paraventricular thalamic nucleus: subcortical
connections and innervation by serotonin, orexin, and
corticotropin-releasing hormone in macaque monkeys. J Comp
Neurol 512:825–848.
Jasmin L, Burkey AR, Granato A, Ohara PT (2004) Rostral
agranular insular cortex and pain areas of the central nervous
system: a tract-tracing study in the rat. J Comp Neurol 468:
425–440.
Jones BE, Yang TZ (1985) The efferent projections from the reticular
formation and the locus coeruleus studied by anterograde
and retrograde axonal transport in the rat. J Comp Neurol 242:
56–92.
Kinomura S, Larsson J, Gulyás B, Roland PE (1996) Activation by
attention of the human reticular formation and thalamic
intralaminar nuclei. Science 271:512–515.
Kolb B, Pellis S, Robinson TE (2004) Plasticity and functions of the
orbital frontal cortex. Brain Cogn 55:104–115.
Krout KE, Belzer RE, Loewy AD (2002) Brainstem projections to
midline and intralaminar thalamic nuclei of the rat. J Comp Neurol
448:53–101.
Li S, Kirouac GJ (2008) Projections from the paraventricular nucleus
of the thalamus to the forebrain, with special emphasis on the
extended amygdala. J Comp Neurol 506:263–287.
Mair RG (1994) On the role of thalamic pathology in diencephalic
amnesia. Rev Neurosci 5:105–140.
Mair RG, Hembrook JR (2008) Memory enhancement with eventrelated stimulation of the rostral intralaminar thalamic nuclei. J
Neurosci 28:14293–14300.
Mair RG, Burk JA, Porter MC (1998) Lesions of the frontal cortex,
hippocampus, and intralaminar thalamic nuclei have distinct
effects on remembering in rats. Behav Neurosci 112:772–792.
McKenna JT, Vertes RP (2004) Afferent projections to nucleus
reuniens of the thalamus. J Comp Neurol 480:115–142.
Mitchell AS, Dalrymple-Alford JC (2005) Dissociable memory effects
after medial thalamus lesions in the rat. Eur J Neurosci
22:973–985.
Mitchell AS, Dalrymple-Alford JC (2006) Lateral and anterior thalamic
lesions impair independent memory systems. Learn Mem
13:388–396.
Newman LA, Burk JA (2005) Effects of excitotoxic thalamic
intralaminar nuclei lesions on attention and working memory.
Behav Brain Res 162:264–271.
Ottersen OP, Ben-Ari Y (1979) Afferent connections to the
amygdaloid complex of the rat and cat. I. Projections from the
thalamus. J Comp Neurol 187:401–424.
Paus T (2000) Functional anatomy of arousal and attention systems
in the human brain. Prog Brain Res 126:65–77.
Phillipson OT, Griffiths AC (1985) The topographic order of inputs to
nucleus accumbens in the rat. Neuroscience 16:275–296.
Reep RL, Winans SS (1982) Afferent connections of dorsal and
ventral agranular insular cortex in the hamster Mesocricetus
auratus. Neuroscience 7:1265–1288.
Reep RL, Corwin JV (1999) Topographic organization of the striatal
and thalamic connections of rat medial agranular cortex. Brain
Res 841:43–52.
Risold PY, Thompson RH, Swanson LW (1997) The structural
organization of connections between hypothalamus and cerebral
cortex. Brain Res Rev 24:197–254.
Schiff ND (2008) Central thalamic contributions to arousal regulation
and neurological disorders of consciousness. Ann N Y Acad Sci
1129:105–118.
Steriade M, Glenn LL (1982) Neocortical and caudate projections of
intralaminar thalamic neurons and their synaptic excitation from
midbrain reticular core. J Neurophysiol 48:352–371.
Steriade M, Oakson G, Ropert N (1982) Firing rates and patterns of
midbrain reticular neurons during steady and transitional states of
the sleep-waking cycle. Exp Brain Res 46:37–51.
Su HS, Bentivoglio M (1990) Thalamic midline cell populations
projecting to the nucleus accumbens, amygdala, and
hippocampus in the rat. J Comp Neurol 297:582–593.
Author's personal copy
136
R. P. Vertes et al. / Neuroscience 219 (2012) 120–136
Sul JH, Kim H, Huh N, Lee D, Jung MW (2010) Distinct roles of rodent
orbitofrontal and medial prefrontal cortex in decision making.
Neuron 66:449–460.
Swanson LW (2004) Brain maps: structure of the rat
brain. New York: Elsevier.
Turner BH, Herkenham M (1991) Thalamoamygdaloid projections in
the rat: a test of the amygdala’s role in sensory processing. J
Comp Neurol 313:295–325.
Van der Werf YD, Weerts JG, Jolles J, Witter MP, Lindeboom J,
Scheltens P (1999) Neuropsychological correlates of a right
unilateral lacunar thalamic infarction. J Neurol Neurosurg
Psychiatry 66:36–42.
Van der Werf YD, Witter MP, Groenewegen HJ (2002) The
intralaminar and midline nuclei of the thalamus. Anatomical and
functional evidence for participation in processes of arousal and
awareness. Brain Res Rev 39:107–140.
Van der Werf YD, Jolles J, Witter MP, Uylings HB (2003)
Contributions of thalamic nuclei to declarative memory
functioning. Cortex 39:1047–1062.
Vertes RP (2002) Analysis of projections from the medial prefrontal
cortex to the thalamus in the rat, with emphasis on nucleus
reuniens. J Comp Neurol 442:163–187.
Vertes RP (2006) Interactions among the medial prefrontal cortex,
hippocampus and midline thalamus in emotional and cognitive
processing in the rat. Neuroscience 142:1–20.
Vertes RP, Martin GF (1988) Autoradiographic analysis of ascending
projections from the pontine and mesencephalic reticular
formation and the median raphe nucleus in the rat. J Comp
Neurol 275:511–541.
Vertes RP, Hoover WB (2008) Projections of the paraventricular and
paratenial nuclei of the dorsal midline thalamus in the rat. J Comp
Neurol 508:212–237.
Vertes RP, Martin GF, Waltzer R (1986) An autoradiographic analysis
of ascending projections from the medullary reticular formation in
the rat. Neuroscience 19:873–898.
Vertes RP, Hoover WB, Do Valle AC, Sherman A, Rodriguez JJ
(2006) Efferent projections of reuniens and rhomboid nuclei of the
thalamus in the rat. J Comp Neurol 499:768–796.
Wouterlood FG (1991) Innervation of entorhinal principal cells by
neurons of the nucleus reuniens thalami. Anterograde PHA-L
tracing combined with retrograde fluorescent tracing and
intracellular injection with Lucifer Yellow in the rat. Eur J
Neurosci 3:641–647.
Wouterlood FG, Saldana E, Witter MP (1990) Projection from the
nucleus reuniens thalami to the hippocampal region: Light and
electron microscopic tracing study in the rat with the anterograde
tracer Phaseolus vulgaris-leucoagglutinin. J Comp Neurol 296:
179–203.
(Accepted 29 April 2012)
(Available online 7 May 2012)