N-甲基-D-天冬氨酸受体在大鼠丘脑前核和扣带后回的表达

目的探讨大鼠丘脑前核和扣带后回内N-甲基-D-天冬氨酸受体NMDAR2A,NMDAR2B及NMDAR1(NR2A.NR2B及NR1)mRNA的表达,从形态学角度为系统研究丘脑前核的功能提供了依据。方法应用原位杂交方法检测丘脑前核及扣带后回内NR2A,NR2B以及NR1 mRNA的表达。结果原位杂交阳性反应产物为棕黄色,主要分布在神经元核周围胞浆中,胞核基本不着色。在丘脑前核,阳性神经元分布较密集,细胞形态较一致。扣带后回皮质阳性神经元在在大脑皮质不同部位分布有差异,分子层染色最弱,外颗粒层密集分布且染色增强,余四层较外颗粒层松散,染色细胞减少。结论 NR2A,NR2B以及NR1广泛分布在丘脑前核和扣带后回。     

Involvement of AMPA/kainate-excitotoxicity in MK801-induced neuronal death in the retrosplenial cortex

MK801 is a prototypical non-competitive NMDA receptor-antagonist that induces behavioural changes and reversible toxicity at low doses, while at higher doses triggers neuronal death that mainly affects the retrosplenial cortex (RSC) and to a lesser extent other structures such as the posterolateral cortical amygdaloid nucleus (PLCo). The mechanism of MK801-induced neurodegeneration remains poorly understood. In this study we analysed the participation of GABA-ergic and glutamatergic neurotransmission in MK801-induced neuronal death. We used a single i.p. injection of MK801 (2.5 mg/kg) that induced moderate neuronal death in the RSC and PLCo of female rats, and combined this treatment with the i.p., i.c.v., or intra-RSC infusion of drugs that are selective agonists or antagonists of the GABA-ergic or glutamatergic neurotransmission. We found that neuronal death in the RSC, but not the PLCo, was significantly reduced by the i.p. injection of thiopental, and the i.c.v. application of muscimol, both GABA-A agonists. MK801-toxicity in RSC was abrogated by intra-RSC infusion of muscimol, but the GABA antagonist picrotoxin had no effect. HPLC-analysis showed that levels of glutamate, but not GABA, in the RSC decreased after i.p. treatment with MK801. Intra-RSC infusion of MK801 did not enhance toxicity triggered by the i.p. injection of MK801, indicating that toxicity is not due to direct blockade of NMDA receptors in RSC neurons. MK801-toxicity in the RSC was abrogated by i.c.v. and intra-RSC infusions of the AMPA/kainate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Interestingly, i.c.v. application of neither muscimol or DNQX inhibited MK801-toxicity in the PLCo, suggesting that the mechanism of neuronal death in the RSC and the PLCo might be different. 1-naphthylacetyl spermine trihydrochloride (NASPM), which blocks Ca2+ permeable AMPA/kainate receptors, also reduced MK801-induced toxicity in the RSC. Intra-RSC infusion of AMPA or kainic acid alone promoted death of RSC neurons and was reminiscent of the degeneration induced by the i.p. treatment with MK801. Collectively, these experiments provide evidence for an AMPA/kainate-dependent mechanism of excitotoxicity in the death of RSC neurons after i.p. treatment with MK801.     

Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Ralpha-independent airway hyperreactivity

The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice.     

Serotonin nerve fibers in the primary visual cortex of the monkey. Quantitative and immunoelectronmicroscopical analysis

Summary A quantitative and immunoelectronmicroscopical analysis of serotonin nerve fibers in the primary visual cortex of the monkey (Macaca fuscata) was made using a sensitive immunoperoxidase method for serotonin. The overall numerical density of serotonin-containing varicosities in the primate striate cortex was approximately 770,000/mm³ and the highest concentration of immunore-active varicosities (ca. 1,400,000/mm³) was observed in the upper portion of layer IVc, the next highest concentration being in layer IVb (ca. 1,180,000/mm³). At the ultrastructural level, the electron dense immunoreactive products were observed in the small granules (10–65 nm in diameter). The varicosities were usually small (0.5–1.0 m in diameter) and made contact with both stellate and pyramidal cells. Serotonin fibers were often in close apposition to the poorly myelinated axons in layers IVb, V, and VI, and they rarely formed distinct synaptic structures with unlabelled neuronal elements.Supported by grant (No. 57214028) from the Ministry of Education, Science and Culture, Japan     

A Golgi deimpregnation study of neurons in the rhesus monkey visual cortex (Areas 17 and 18)

Summary The morhological features of 298 neurons impregnated according to Golgi-Kopsch in areas 17 and 18 of Macaca mulatta were analyzed, and the same neurons were deimpregnated to visualize structural details of the somata in different types of neurons. The following cell types were investigated: Pyramidal and pyramid-like cells, spiny stellate cells, double bouquet cells, bipolar cells, chandelier cells, neurogliaform cells, basket and related cells. This procedure allows the evaluation of the nuclear-cytoplasmic proportion and the position of the nucleus besides shape and size of the cell body. Pyramidal and pyramid-like cells (N=43), spiny stellate cells (N=26), basket and related cells (N=126) are variable in these features. A positive correlation between soma size and width of the cytoplasm is found in pyramidal, pyramid-like cells and spiny stellate cells. With the exception of some large somata in both these types of neurons the nucleus is found in a central position. Double bouquet cells (N=6), bipolar cells (N=13) and chandelier cells (N=11) exhibit small cytoplasmic rims and centrally located nuclei. The small somata of neurogliaform cells (N=37), however, and the small to very large somata of basket and related cells show broad cytoplasmic portions surrounding the eccentrically located nuclei. These findings allow the identification of different neuronal types in Nisslstained sections on the basis of these soma features. This is a prerequisite for further detailed quantitative studies on the laminar distribution of different neuronal types in the visual cortex of the monkey.     

人巨细胞病毒感染胎鼠大脑皮质神经元显微和超微结构观察

目的：研究人巨细胞病毒（HCMV）经小鼠胎盘垂直传播致胎鼠大脑皮质神经元病理改变的显微和超微结构特征。方法：在8－12周龄Balb/c雌雄小鼠腹腔内接种HCMV后,交配,特孕鼠临产时剖腹取出10份胎鼠双侧大脑皮质,用光镜和透射电射观察了神经元的显微和超微结构,同时进行了病毒分离。结果：光镜下可见胎脑微血管扩张充血,神经元数目明显减少,残存的神经元缺血性改变,间质水肿;可见到软化灶及受染神经元核内及胞质内HCMV特征性哮碱性和哮酸性包涵体,电镜下可见受染神经元核仁消失,胞质内线粒体,内质网和高尔基复合体等重要细胞器结构严重破坏呈空泡状或溶解;并找到人类疱疹病毒样颗粒。病毒分离阳性,在同时设置的正常对照组则无上述阳性发现。结论：HCMV能通过小鼠胎盘感染子代胎鼠大脑皮质神经元,并导致神经元结构破坏死亡。     

Architectonic Subdivisions of Neocortex in the Gray Squirrel (Sciurus carolinensis)

Squirrels are highly visual mammals with an expanded cortical visual system and a number of well‐differentiated architectonic fields. To describe and delimit cortical fields, subdivisions of cortex were reconstructed from serial brain sections cut in the coronal, sagittal, or horizontal planes. Architectonic characteristics of cortical areas were visualized after brain sections were processed with immunohistochemical and histochemical procedures for revealing parvalbumin, calbindin, neurofilament protein, vesicle glutamate transporter 2, limbic‐associated membrane protein, synaptic zinc, cytochrome oxidase, myelin or Nissl substance. In general, these different procedures revealed similar boundaries between areas, suggesting that functionally relevant borders were being detected. The results allowed a more precise demarcation of previously identified areas as well as the identification of areas that had not been previously described. Primary sensory cortical areas were characterized by sparse zinc staining of layer 4, as thalamocortical terminations lack zinc, as well as by layer 4 terminations rich in parvalbumin and vesicle glutamate transporter 2. Primary areas also expressed higher levels of cytochrome oxidase and myelin. Primary motor cortex was associated with large SMI‐32 labeled pyramidal cells in layers 3 and 5. Our proposed organization of cortex in gray squirrels includes both similarities and differences to the proposed of cortex in other rodents such as mice and rats. The presence of a number of well‐differentiated cortical areas in squirrels may serve as a guide to the identification of homologous fields in other rodents, as well as a useful guide in further studies of cortical organization and function. Anat Rec, 291:1301–1333, 2008. © 2008 Wiley‐Liss, Inc.     

Bcl-2 immunoreactivity in salivary gland neoplasms is unrelated to the expression of mRNA for natural killer cell stimulatory cytokines interleukin (IL)-2 and IL-12

Certain cytokines are involved in the generation of natural killer (NK) cells and participate in the regulation of the proto-oncogene bcl-2. We aimed to study the mRNA expression of interleukin (IL) -2, IL-4 and IL-5, the composition of the tumour infiltrating lymphocytes (TIL), and the expression of bcl-2 in 14 benign and malignant human parotid tumours. T IL were predominantly composed of T lymphocytes and NK cells. We found evidence for the homing of T cells, and for generation of NK cells in the vicinity of the tumours. mRNA for IL-2 and IL-12, were identified but IL-4 mRNA was not found. The cytokine profiles and the composition of TIL of the two tumour categories were indistinguishable, suggesting that these host-response variables do not explain the differences in biological behaviour of these particular tumours. The results support a shift towards Th1 (T helper 1) cells and interferon- production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases. Most infiltrating lymphocytes showed strong expression of bcl-2; an interesting observation with regard to lymphocytic apoptosis in neoplastic diseases. The immunoreactivity fot the bcl-2 protein varied considerably between and within tumours, and almost all benign tumours showed strong bcl-2 positively whereas several of the malignant tumours showed weak or absent staining. The variable expression of bcl-2 protein suggests a different susceptibility of tumour cells to apoptosis. The results also indicate that bcl-2 cannot play a major role as protective agent in the specific apoptotic pathway induced by NK cells.     

Alveolar macrophage interleukin (IL)-10 and IL-12 production in atopic asthma

Inflammation in asthma is characterized by a Th2 response. In many experimental systems, this response can be regulated by interleukin (IL)-IO and IL-12. IL-10 deactivates T cells, and IL-12 reorients the response toward a Till pattern. Alveolar macrophages (AM) can secrete both of these cytokines, and thus regulate T-cell behavior in asthma. They can enhance the Tli2 response by turning off their secretion of IL-10 and IL-12. or tend to downregulate it by producing these cytokines. To elucidate that point, we assayed the AM IL-10 and IL-12 from 11 asthmatic patients and four controls. Six asthmatics were treated by inhaled corticosteroids. AM were recovered by bronchoalveolar lavage (BAL). They were isolated and cultured for 24 h without stimulation or in the presence of lipopolysaccharide (LPS), IL-10 and the p40 subunit of IL-12 were assayed in the BAL fluid and i n AM culture supernatants by ELISA. Spontaneous AM IL-10 production was higher in asthmatics, particularly in the treated group. The AM IL-10 production after stimulation by LPS was also elevated in asthmatics, but was mainly so in untreated patients. IL-12 levels were higher in BAL fluids from untreated patients than from controls. The IL-12 production of LPS-stitnulated-AM from these patients was increased. These results show that AM are at least primed for the production of IL-10 and IL-12 in asthma, and suggest that these cells could be involved in the resolution of the asthmatic inflammation.     

Polymorphism of age-related changes in interleukin (IL) production: differential changes of T helper subpopulations, synthesizing IL 2, IL 3 and IL 4

Inbred mice were examined for strain differences in age-associated changes in the capacity to synthesize interleukin (IL), i.e. IL 2, IL 3 and IL 4 after stimulation with phorbol myristate acetate (PMA) and calcium ionophore (A23187). Production of IL 2 remains constant in A/J, DBA/1 and DBA/2 mice and decreases with age in one of the strains examined (C57BL/6J). Strain differences in age-associated change of synthesis did not show the relation between youthful synthetic capacity and magnitude of later decrease ("economic correction") which is observed in several other systems. This difference between different types of polymorphisms is attributed to an age-associated defect in intrinsic capacity to synthesize IL 2 which may occur in only one of the tested strains, C57BL/6J. In contrast to IL 2 production, the quantities of IL 3 and IL 4 increase progressively, with advancing age, in mice of the three strains tested. T cells from old mice contain a greater frequency of cells producing IL 3, than do those of young mice. In addition, synthesis of IL 3 is induced at a relatively lower concentration of PMA in cells from old animals and this may be a consequence of different signal requirements of the two subsets of the T helper cells, but also a change in intrinsic properties of these cells. Since IL 3 and IL 4 production, but not IL 2 production, increases with age, it is reasonable to conclude that this reflects an expansion of a T helper cell population which secretes IL 3 and IL 4, but not IL 2, presumably TH2.     

Airway hyperresponsiveness and airway obstruction in transgenic mice. Morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung

Understanding the sources of variation in airway reactivity and airflow is important for unraveling the pathophysiology of asthma, obstructive lung disease, and other pulmonary disorders. Transgenic expression of two closely related cytokines in the mouse lung produced opposite effects on these parameters. Interleukin (IL)-6 did not alter basal airways resistance and decreased methacholine responsiveness, whereas IL-11 caused airways obstruction and increased airway responses to methacholine. To clarify these differences we examined histologic sections and used morphometry to compare bronchiolar and parenchymal dimensions in 1- to 2-mo-old transgenic mice expressing IL-6 or IL-11 and littermate control mice. Both transgenic strains showed similar emphysema-like airspace enlargement, nodular peribronchiolar collections of mononuclear cells, thickening of airway walls, and subepithelial airway fibrosis. When compared with littermate control mice, the IL-6 mice showed an approximately 50% increase in the caliber of their bronchioles and an increase in airway wall thickness that was in proportion to the increase in the size of their airways. In contrast, the remodeling response was more robust in the IL-11 transgenic mice. It was also seen in airways with normal external and luminal diameters and thus was out of proportion to the caliber of their airways. These results support the hypothesis that structural alterations and resulting caliber changes of respiratory airways can have important effects on airway physiology and reactivity.     

Concanavalin A-induced hepatitis in mice is prevented by interleukin (IL)-10 and exacerbated by endogenous IL-10 deficiency

One single intra-venous (i.v.) injection of Concanavalin A (Con A) into mice provokes a cell-mediated immunoinflammatory hepatitis. We have presently evaluated the immunopharmacological effects of exogenous interleukin (IL)-10 and the role of endogenous IL-10 in this model by using exogenous IL-10, anti-IL-10 monoclonal antibody (mAb) and mice with disrupted IL-10 gene (IL-10 KO mice). Whilst exogenous IL-10 administered in a prophylactic (1 h prior to Con A) and even "early" therapeutic fashion (30 min after Con A) reduced the elevation of transaminase activities in plasma in a dose-dependent manner, observed in control mice, these biochemical markers of liver injury were significantly increased both in IL-10 KO mice as well as in those receiving anti-IL-10 mAb. Interestingly, doses of Con A lower than 20 mg/kg that were only capable of inducing slight serological signs of hepatitis in mice, exerted marked hepatitic effects when administered to either anti-IL-10 mAb-treated mice or to IL-10 KO mice. The disease modulating effects of exogenous IL-10 and either genetical or pharmacologically-induced IL-10 deficiency were associated with profound and opposite modifications of the Con A-induced increase in the circulating levels of IFN-gamma and TNF-alpha. Relative to control animals, the blood levels of these cytokines were diminished in IL-10-treated mice and augmented in both IL-10 KO mice and anti-IL-10 mAb-treated mice. These results prove the physiological antiinflammatory role of endogenous IL-10 in Con A induced hepatitis and the beneficial effects of IL-10 treatment to prevent this condition.     

Developmental changes in concentrations and distributions of neurotrophins in the monkey cerebellar cortex

Neurotrophins are involved in the survival, differentiation, migration and neurite outgrowth of various neuronal populations. Neurotrophins and their receptors are widely expressed in the developing cerebellum of various experimental animals. To gain some insight into the possible roles played by these molecules in monkey cerebellum, we examined the protein levels of BDNF, NT-4/5 and NT-3 and distributions of those neurotrophins and TrkC, a high affinity receptor for NT-3, in the cerebellum of developing macaque monkeys using ELISAs and immunohistochemical methods. We found that the level of BDNF increased during development, while the level of NT-3 was higher during embryonic stages and decreased toward adulthood. The level of NT-4/5 increased from embryonic stages to infant stages and gradually declined with age. Among the three neurotrophins, BDNF immunoreactivity was found in all kinds of cerebellar neurons, including all inhibitory interneurons, throughout the postnatal periods examined, indicating that BDNF may be an essential factor for the maintenance of cerebellar neural functions. The Bergmann glial fibers and the internal part of the external granule cell layer were strongly NT-3 immunopositive at the early postnatal stages, and more weakly immunoreactive toward adulthood. In addition, we found that the premigratory precursors of the granule cells were TrkC immunopositive at early postnatal stages. These findings suggest that NT-3 in Bergmann glial fibers may be involved in the migration of the premigratory granule cells.     

Posterior cingulate and retrosplenial cortex connections of the caudal superior temporal region in the rhesus monkey

The rostral part of the superior temporal gyrus (STG) is known to project to ventral temporal cortex, but analogous paralimbic connections of the caudal STG have received comparatively less attention. The present study of the connections of the STG with medial paralimbic cortex showed that the caudal part of the STG (area Tpt and caudal area paAlt) and adjacent cortex of the upper bank of the superior temporal sulcus (caudal area TPO) have reciprocal connections with the caudal cingulate gyrus (areas 23a, b and c), retrosplenial cortex (area 30), and area 31. By contrast, cortex of the rostral-to-mid STG (areas Ts2, Ts3, and the rostral part of area paAlt) and adjacent upper bank of the STS (mid-area TPO) have few, if any, such interconnections. It is suggested that this connectional pattern of the caudal STG is consistent with its putative role of localizing sounds in space as proposed in recent studies.     

Ultrastructural changes associated with reversible and irreversible suppression of electrical activity in olfactory cortex slices

Summary The fine structure and electrical activity were studied in thin brain sections prepared from the olfactory cortex of the guinea pig and incubated in vitro in standard and modified conditions. In the standard medium, the potential response was maintained with no marked changes for 4–5 hours and thereafter gradually decreased. The ultrastructure of the tissue was well preserved for the initial 2 hours of incubation. After incubation for 5 hours, many empty spaces were noted. Some dendritic stumps lost fine internal structure, but most of the synapses were apparently normal. Cyanide suppressed the potential response, and caused swelling of the nerve terminals and a decrease in the number of synaptic vesicles. The recovery of the response in the standard medium was not accompanied by a full restoration in the fine structure. If slices were incubated in the absence of glucose and oxygen, with cyanide in glucose-free medium, or at a low temperature, the potential response was irreversibly depressed. In these slices, numerous wide spaces of low electron density were noted which were concluded to have been derived, at least partly, from the swollen dendrites.Dedicated to Professor Toshihiko Tokizane on the occasion of his 60th birthday.     

The distribution of degenerating axons after small lesions in the intact and isolated visual cortex of the cat

Summary The extent of the spread of axonal degeneration was investigated in the visual cortex of the cat after making small lesions restricted to the grey matter. Two series of experiments were undertaken. In the first, normal adult cats were used, and in the second, the cortex of the postlateral gyrus was isolated from its extrinsic afferents by surgical undercutting 3 months before making the lesions. The results were similar in the two series in most respects. 1. Horizontal fibres extended in considerable numbers for some 500 m from the lesion, mainly in layers I, III/IV and V, a few reaching 2–3 mm. These fibres were better seen in the intact than in the isolated cortex. Their spread was usually asymmetrical, being greater posteromedially than anterolaterally. 2. Oblique axons ran downwards from the middle layers into layers V and VI, or upwards into layers I and II. 3. Axons arising from layers II to VI descended vertically into the white matter. Degeneration patterns after lesions in areas 17 and 18 were compared.     

Architectonic Subdivisions of Neocortex in the Tree Shrew (Tupaia belangeri)

Tree shrews are small mammals that bear some semblance to squirrels, but are actually close relatives of primates. Thus, they have been extensively studied as a model for the early stages of primate evolution. In this study, subdivisions of cortex were reconstructed from brain sections cut in the coronal, sagittal, or horizontal planes, and processed for parvalbumin, SMI‐32‐immunopositive neurofilament protein epitopes, vesicle glutamate transporter 2 (VGluT2), free ionic zinc, myelin, cytochrome oxidase, and Nissl substance. These different procedures revealed similar boundaries between areas, suggesting the detection of functionally relevant borders and allowed a more precise demarcation of cortical areal boundaries. Primary cortical areas were most clearly revealed by the zinc stain, because of the poor staining of layer 4, as thalamocortical terminations lack free ionic zinc. Area 17 (V1) was especially prominent, as the broad layer 4 was nearly free of zinc stain. However, this feature was less pronounced in primary auditory and somatosensory cortex. In primary sensory areas, thalamocortical terminations in layer 4 densely express VGluT2. Auditory cortex consists of two architectonically distinct subdivisions, a primary core region (Ac), surrounded by a belt region (Ab) that had a slightly less developed koniocellular appearance. Primary motor cortex (M1) was identified by the absence of VGluT2 staining in the poorly developed granular layer 4 and the presence of SMI‐32‐labeled pyramidal cells in layers 3 and 5. The presence of well‐differentiated cortical areas in tree shrews indicates their usefulness in studies of cortical organization and function. Anat Rec, 2009. © 2009 Wiley‐Liss, Inc.     

Interrelationships between interleukin (IL)-1, IL-6 and IL-8 in synovial fluid of various arthropathies

High levels of many cytokines, including interleukin (IL)-1, IL-6 and IL-8, were found in various arthropathies suggesting that they play a role in the pathogenesis of disease, although their relationship with the type and activity of disease is still not clear. The synovial fluid (SF) of 24 patients with rheumatoid arthritis (RA), 19 with psoriatic arthritis (PA) and 33 with osteoarthritis (OA) was analyzed for IL-1, IL-6 and IL-8. The highest concentration of the three cytokines was found in the SF of RA. IL- detectable levels (>-20 pg/ml) were observed in 8/24 (33.3%) patients with RA, in one patient with PA but in no patient with OA.IL-6 (mean±SD) (1610.37±1781.65 pg/ml) was higher in RA than in PA (672.47±867.40 pg/ml,p=0.043) and OA (89.45±120.52 pg/ml,p=0.0001). IL-8 (1042.72±698.64 pg/ml) was higher in RA than in PA (660.36±625.11 pg/ml,p=0.03) and OA (89.9±45.88 pg/ml,p=0.0001). A correlation between IL-1, IL-6 and IL-8 was found in RA. In all patients a correlation between IL-6 and IL-8 levels was found; moreover, these two cytokines were associated with SF indices of inflammation, such as white blood cells (WBC) count and total protein (TP) concentration.Out findings suggest that these interrelationships play a role in the evolution of more severe erosive arthropathy such as RA.     

Dual axonal terminations from the retrosplenial and visual association cortices in the laterodorsal thalamic nucleus of the rat

Light and electron microscopic tracing studies were conducted to assess the synaptic organization in the laterodorsal thalamic nucleus (LD) of the rat and the laminar origins of corticothalamic terminals from the retrosplenial and visual association cortices to LD. A survey of the general ultrastructure of LD revealed at least three types of presynaptic terminals identified on the basis of size, synaptic vesicle morphology, and synaptic membrane specializations: (1) small axon terminals with round synaptic vesicles (SR), which accounted for the majority of terminal profiles and made asymmetric synaptic contacts predominantly with small dendritic shafts and spines; (2) large axon terminals with round synaptic vesicles (LR), which formed asymmetric synaptic contacts mainly with large dendritic shafts; and (3) small to medium-size axon terminals with pleomorphic synaptic vesicles (SMP), which symmetrically synapsed with a wide range of postsynaptic structures from cell bodies to small dendrites. Synaptic glomeruli were identified, whereas no presynaptic dendrites were found. To characterize and identify corticothalamic terminals arising from the retrosplenial and visual association cortices that project to LD, wheat germ agglutinin conjugated to horseradish peroxidase (WGA–HRP) was injected into these cortices. Axons anterogradely labeled with WGA–HRP ended in both SR and LR terminals. On the other hand, dextran-tetramethylrhodamine injected into LD as a retrograde fluorescent tracer labeled large pyramidal cells of layer V as well as small round or multiform cells of layer VI in the retrosplenial and visual association cortices. These findings provide the possibility that corticothalamic terminations from cortical neurons in layer V end as LR terminals, while those from neurons in layer VI end as SR boutons.