Thalamic and cortical afferents differentiate anterior from posterior cingulate cortex in the monkey.

The anterior cingulate cortex receives thalamic afferents mainly from the midline and intralaminar nuclei rather than the anterior thalamic nuclei. In contrast, the posterior cingulate cortex receives afferents primarily from the anterior thalamic nuclei and from extensive cortical areas in the frontal, parietal, and temporal lobes. These contrasting afferents may provide a structural basis for pain-related functions of the anterior cingulate cortex.

Glomerular inflammation induces resistance to tubular injury in the rat. A novel form of acquired, heme oxygenase-dependent resistance to renal injury.

Considerable attention is directed to a surprising biologic phenomenon wherein tissues exposed to one insult acquire resistance to another. We identify a novel example of acquired resistance to acute renal failure and a mechanism that contributes to such resistance. Nephrotoxic serum, administered to rats 24 h before the induction of glycerol-induced acute renal failure, reduces functional and structural injury that occurs in this model. Since heme oxygenase, the rate-limiting enzyme in heme degradation, protects against heme protein-induced renal injury, we questioned whether induction of heme oxygenase underlies the protection afforded by nephrotoxic serum. Kidney heme oxygenase (HO-1) mRNA was induced 6 h after nephrotoxic serum and renal tubules were identified as the site of expression of heme oxygenase protein. Induction of heme oxygenase was accompanied by increased renal content of ferritin but not by induction of other antioxidant enzymes. Inhibition of heme oxygenase prevented the protection afforded by nephrotoxic serum. Nephrotoxic serum did not protect against ischemic acute renal failure, a model in which heme oxygenase is not induced. Thus, nephrotoxic serum protects against glycerol-induced acute renal failure by inducing heme oxygenase in tubules. This study provides the first demonstration of resistance to tubular injury acquired from glomerular inflammation, uncovers a mechanism for such resistance, and exposes the dialogue that occurs between glomeruli and tubules.

Incidence and risk factors of urinary tract infection in very low birth weight infants.

OBJECTIVES: To describe the incidence and associated risk factors of urinary tract infection (UTI) in very low birth weight (VLBW) infants and to determine the value of diagnostic imaging studies after the first UTI episode before discharge from the neonatal intensive care unit (NICU). METHODS: VLBW infants born during 2003-2012 were reviewed for UTI. In a nested case-control study, potential risk factors of UTI were compared between infants with UTI (cases) versus birth weight and gestational age matched controls. Renal ultrasonography (USG) and voiding cystourethrography (VCUG) results were reviewed in cases. RESULTS: During the study period, 54.7% of urine culture specimens were collected by sterile methods. 3% (45/1,495) of VLBW infants met the study definition for UTI. UTI was diagnosed at mean postnatal age of 33.1±22.9 days. There was no significant difference in gender, ethnicity, antenatal steroid exposure, blood culture positive sepsis, ionotropic support, respiratory support and enteral feeding practices between cases and controls. Cases had a significantly higher cholestasis compared to controls (22% vs. 9% ; p = 0.03). However, cholestasis was not a significant predictor of UTI in the adjusted analysis [adjusted OR 2.38 (95% CI 0.84 to 6.80), p = 0.11]. Cases had higher central line days, parenteral nutrition days, total mechanical ventilation days, chronic lung disease, and length of stay compared to controls. Renal USG was abnormal in 37% and VCUG was abnormal in 17% of cases. CONCLUSIONS: The incidence of UTI in contemporary VLBW infants is relatively low compared to previous decades. Since no significant UTI predictors could be identified, urine culture by sterile methods is the only reliable way to exclude UTI. The majority of infants with UTI have normal renal anatomy. UTI in VLBW infants is associated with increased morbidity and length of stay.

Retrosplenial cortex in the rhesus monkey: a cytoarchitectonic and Golgi study.

The laminar and cellular structure of retrosplenial cortex in the rhesus monkey was studied with Nissl stained and rapid Golgi impregnated tissue and the results were used to evaluate morphological features of a cortical transition zone. The granular layer of retrosplenial granular cortex is composed primarily of small, density packed, star pyramidal cells. These cells branch within the granular layer itself, while the apical dendrite enters layer I where it branches infrequently or not at all. This cell type is similar to the star pyramid first described by Lorente de No except in its areal and laminar distribution. Cytoarchitectonic observations of retrosplenial agranular cortex show, that, although this area is relatively "agranular" in comparison to other cortical areas, it does possess an incipient layer II and layer IV. These layers are composed mainly of small and medium sized pyramidal cells, but many non-pyramidal cell types were found in these and other layers in this area in rapid Golgi preparations. Stellate cells with beaded or smooth, lightly spinous dendrites were found throughout layer I-IV, while fusiform cells with smooth or very lightly spinous dendrites appear in layers III-VI. Areas surrounding retrosplenial cortex in the posterior cingulate region were also evaluated in Nissl and Golgi preparations including the indusium griseum, subiculum (dorsal to the corpus callosum) and area 23. The laminar and cellular constitutents of retrosplenial cortex were then evaluated in the context of cortical architectonic transition. The transition from one cellular layer in the indusium griseum to five cellular layers in area 23 is made by the addition of layers II, III, IV and VI in retrosplenial cortex to the one ganglionic layer of the indusium griseum and subiculum. Besides the addition and subdivision of layers in retrosplenial cortex, two aspects of cell morphology were found to change in this region. First, the structure of pyramidal cells progressively changes from those in the indusium griseum which have predominently round or oval somata and a preponderance of apical and few basal dendrites to those in layer V of retrosplenial cortex and area 23 which have pyramidal shaped somata and a great number of basal dendrites which branch frequently and spread horizontally for hundreds of microns. Second, there is a change in the number and distribution of non-pyramidal cell types. Evidence was not found that the indusium griseum, dorsal subiculum or layer V of retrosplenial granular cortex contain a significant number of stellate or fusiform cells. At the retrosplenial granular/agranular border, though, these cells gradually begin to constitute a greater proportion of the cell population and in area 23 form a major component of layer IV...

Cortical connections between rat cingulate cortex and visual, motor, and postsubicular cortices.

The connections of rat cingulate cortex with visual, motor, and postsubicular cortices were investigated with retrograde and anterograde tracing techniques. In addition, connections between visual and the postsubicular (area 48) and parasubicular (area 49) cortices were evaluated with the same techniques. The following conclusions were drawn. Area 29 connections: Afferents to area 29 originate mainly from cingulate areas 24 and 25, visual cortex (primarily area 18b), motor cortex area 8, area 11 of frontal cortex, areas 48 and 49, and the subiculum. Efferent connections of area 29 within cingulate cortex and to visual areas differ for each cytoarchitectural subdivision of area 29. Thus, area 29c has limited projections both within cingulate cortex and to areas 48 and 49, while area 29d projects to these areas as well as to area 8, area 18b, and medial area 17. These visual cortex afferents originate mainly from layer V neurons of areas 29b and 29d, while areas 29a and 29c have virtually no projections to visual cortex. Area 24 connections: Afferents to area 24 originate primary from cingulate areas 25 and 29 and visual area 18b and medial area 17. Efferent projections of area 24a are distributed within cingulate cortex, while area 24b has more extensive projections to posterior cingulate and visual cortices. Area 24b is the cingulate subdivision which is both the primary recipient of visual cortex afferents as well as the source of most of the projections of anterior cingulate cortex to visual areas. Visual cortex has reciprocal connections with parts of the postsubicular and parasubicular cortices. Neurons of the internal pyramidal cell layer of both areas 48 and 49 project to areas 17 and 18b, while layers I and III of these parahippocampal areas receive projections from areas 17 and 8b. In conclusion, areas 29d have particularly extensive interconnections with visual cortex, while area 29d also maintains projections to area 8 of motor cortex. This connection scheme supports the view that cingulate cortex may have a role in feature extraction from the sensory environment, as well as in sensorimotor integration. Finally, the postsubiculum may be classified as a limbic association cortex in which extensive visual and cingulate efferents converge.

Afferent connections of anterior thalamus in rats: sources and association with muscarinic acetylcholine receptors.

Afferent connections of the anterior thalamic nuclei (ATN) are classically thought to originate in the mammillary body and limbic cortex. This study explores nonlimbic sources of ATN afferents by using retrograde transport of horseradish peroxidase (HRP) to ascertain the relative contribution of these connections. Spread of HRP into adjacent regions was prevented either by removing the overlying cortex or by injecting through permanently implanted cannulas. The main sources of nonlimbic ATN afferents are the pretectum and central gray. Pretectal neurons were HRP-labeled primarily in the contralateral medial pretectal nucleus with a smaller number in the ipsilateral posterior pretectal nucleus. In the central gray, labeled cells were concentrated ipsilaterally in the laterodorsal tegmental nucleus. Additional projections to ATN originate in the reticular and ventral lateral geniculate nuclei of the thalamus, raphe nuclei, peripontine tegmental nucleus, and locus coeruleus. The association of ATN afferents with muscarinic receptors was also explored by means of in vitro receptor autoradiography with the muscarinic ligands propylbenzilylcholine mustard (PrBCM) and pirenzepine (PZ) in normal rats and rats with ablations. Ibotenic acid injections into ATN were used to destroy intrinsic neurons while leaving afferent fibers intact. Whereas such ablations produced statistically significant decreases in PrBCM binding in the anterior dorsal (AD, -45%) and anterior ventral, magnocellular part (AVm, -51%) nuclei, binding in the anterior ventral, parvicellular part (AVp) and anterior medial (AM) nuclei was not significantly decreased. Furthermore, PZ binding in normal rat ATN was significantly less (-72%) than PrBCM binding. These results suggest that a major proportion of muscarinic binding is associated with presynaptic elements. Ibotenic acid ablations of the mammillary body reduced PrBCM binding in ATN whereas lesions in cingulate cortex and laterodorsal tegmental nucleus had no effect. Compared to sham lesion controls, mammillary body lesions resulted in statistically significant decreases in binding bilaterally in AD (-15%), AVm (-19%), and AM (-20%). In conclusion, ATN receive afferents from several nonlimbic regions. Of these inputs, the pretectum may be the primary route through which sensory information reaches ATN. In addition, cholinergic input may modulate activity in projections from the mammillary body to ATN through presynaptic muscarinic receptors.

Cingulate cortex of the rhesus monkey: II. Cortical afferents.

Cortical projections to subdivisions of the cingulate cortex in the rhesus monkey were analyzed with horseradish peroxidase and tritiated amino acid tracers. These projections were evaluated in terms of an expanded cytoarchitectural scheme in which areas 24 and 23 were divided into three ventrodorsal parts, i.e., areas 24a-c and 23a-c. Most cortical input to area 25 originated in the frontal lobe in lateral areas 46 and 9 and orbitofrontal areas 11 and 14. Area 25 also received afferents from cingulate areas 24b, 24c, and 23b, from rostral auditory association areas TS2 and TS3, from the subiculum and CA1 sector of the hippocampus, and from the lateral and accessory basal nuclei of the amygdala (LB and AB, respectively). Areas 24a and 24b received afferents from areas 25 and 23b of cingulate cortex, but most were from frontal and temporal cortices. These included the following areas: frontal areas 9, 11, 12, 13, and 46; temporal polar area TG as well as LB and AB; superior temporal sulcus area TPO; agranular insular cortex; posterior parahippocampal cortex including areas TF, TL, and TH and the subiculum. Autoradiographic cases indicated that area 24c received input from the insula, parietal areas PG and PGm, area TG of the temporal pole, and frontal areas 12 and 46. Additionally, caudal area 24 was the recipient of area PG input but not amygdalar afferents. It was also the primary site of areas TF, TL, and TH projections. The following projections were observed both to and within posterior cingulate cortex. Area 29a-c received inputs from area 46 of the frontal lobe and the subiculum and in turn it projected to area 30. Area 30 had afferents from the posterior parietal cortex (area Opt) and temporal area TF. Areas 23a and 23b received inputs mainly from frontal areas 46, 9, 11, and 14, parietal areas Opt and PGm, area TPO of superior temporal cortex, and areas TH, TL, and TF. Anterior cingulate areas 24a and 24b and posterior areas 29d and 30 projected to area 23. Finally, a rostromedial part of visual association area 19 also projected to area 23. The origin and termination of these connections were expressed in a number of different laminar patterns. Most corticocortical connections arose in layer III and to a lesser extent layer V, while others, e.g., those from the cortex of the superior temporal sulcus, had an equal density of cells in both layers III and V.(ABSTRACT TRUNCATED AT 400 WORDS)

Lateral magnocellular thalamic nucleus in rabbits: architecture and projections to cingulate cortex.

The lateral magnocellular nucleus (LM) contains the largest neurons in the rabbit thalamus, yet its cortical connections have not been described. This study evaluates the architecture, cingulate cortical connections, and spontaneous rate of neuronal discharges in LM. At its maximal mediolateral extent in coronal sections, LM underlies the laterodorsal and lateroposterior nuclei. It has a short medial and long lateral limb, both of which have high levels of cytochrome oxidase activity. On the basis of horseradish peroxidase and fluorescent dye injections, LM projects primarily to area 29 and posterior area 24. Projections to area 29d are topographically organized so that the medial limb of LM projects to rostral area 29d, mid levels of LM where the limbs join project to midlevels of area 29d and lateral parts of the lateral limb project to posterior area 29d. It is mainly the midportion of the lateral and medial limbs that projects to areas 29b and 29c. The anterior parts of these areas receive input from dorsal parts of LM, whereas posterior levels of these areas receive input from ventral LM. The midregion of LM also projects to caudal area 24. Injections of 3H-amino acids into area 29d anterogradely label neuronal processes in LM. Finally, single unit electrophysiological recordings from LM in halothane-anesthetized rabbits showed a unique pattern of spontaneous discharges. Over 70% of the LM neurons cycled through a number of different phases with a mean +/- S.E.M. peak discharge rate of 31 +/- 4.7 Hz. This high rate contrasts with the 17.6 +/- 3.2 Hz rate for neurons that maintained a constant rate of discharge and the 7.5 +/- 1.3 Hz rate of discharges for neurons in nuclei dorsal and ventral to LM. LM neurons are large, have high levels of cytochrome oxidase and spontaneous activity, and project extensively to the posterior cingulate cortex. These features suggest that LM neurons are highly active metabolically and may be fast conducting efferents to cingulate cortex.

Distribution of muscarinic acetylcholine receptors on processes of isolated retinal cells.

Binding of propylbenzilylcholine mustard, a muscarinic acetylcholine receptor antagonist, to isolated retinal cells was examined with light microscopic autoradiography. Dissociation of the adult tiger salamander retina yielded identifiable rod, cone, horizontal, bipolar, amacrine/ganglion, and Müller cells. Preservation of fine structure was assessed with conventional electron microscopy. For all cell types, the plasmalemma was intact and free of adhering debris; in addition, presynaptic ribbon complexes were present in photoreceptor and bipolar axon terminals indicating that synaptic structures were retained. Specific binding to cell bodies and processes was analyzed separately by using morphometric and statistical techniques. The highest grain densities occurred on processes of amacrine/ganglion cells and axons and 2 degrees and 3 degrees dendrites of bipolar neurons. Bipolar cells, however, seemed to be a heterogeneous population because there was great variation in the density of binding sites on both their axons and distal dendrites. Intermediate levels of binding were found on bipolar 1 degree dendrites and horizontal cells. No specific binding was detected on Müller cells and most parts of photoreceptors. Comparisons between cells showed that grain densities were similar for bipolar axons and amacrine/ganglion cell processes but bipolar dendrites were richer in binding sites than horizontal cell dendrites. Thus, muscarinic receptors in the salamander retina are located on amacrine/ganglion, bipolar, and horizontal cells and primarily confined to the processes which compose the two synaptic layers. In the inner plexiform layer, muscarinic receptors reside on processes from all three inner retinal neurons: in the outer synaptic layer, receptors are only on second-order cells and are more numerous along bipolar than horizontal cell dendrites.

Direct connections of rat visual cortex with sensory, motor, and association cortices.

Each division of rat visual cortex, areas 17, 18a, and 18b, has connections with sensory, motor, and association cortices. These corticocortical connections were sampled using anterograde autoradiographic and retrograde horseradish peroxidase labeling techniques. Area 17 is connected via reciprocal pathways with each division of visual cortex, the posterior one-third of motor area 8, association area 7, and posteroventral area 36 of temporal cortex. It also receives projections from perirhinal areas 13 and 35. Area 18a has reciprocal connections with areas 17 and 18b, a patch in posterior somatosensory area 3, and dorsal auditory area 41. Like area 17, area 18a receives afferents from and projects to the posterior one-third of motor area 8. The connections of area 18a with association cortices are extensive; these regions include parietal areas 7, 39, 40, and 14, posteroventral and dorsal area 36, and perirhinal cortex. Area 18b is connected with areas 17 and 18a, a patch in medial area 3, and dorsal area 41. There are reciprocal projections between area 18b and posterior area 8. As for association cortex, area 18b projects to frontal area 11, area 7, posteroventral and dorsal area 36, and perirhinal cortex. In addition, area 18b receives input from and projects efferents to the dorsal claustrum. Most of the interconnections among areas 17, 18a, and 18b originate from neurons in layers II, III, and V and end in terminal fields in layers I-III and V. In contrast, projections of other sensory, motor, and association cortices to visual cortex originate mainly from neurons in layer V and to a lesser extent from layer II. The reciprocal pathways from visual cortex terminate predominantly in the supragranular layers. In conclusion, these corticocortical pathways provide the basis for cortical visuosensory and visuomotor integration that may aid the rat in the coordination of visually guided behaviors.

Synaptic termination of thalamic and callosal afferents in cingulate cortex of the rat.

The distribution of degenerating thalamic and callosal afferents to cingulate cortex in the rat is analyzed. Both light microscopic silver impregnation and quantitative electron microscopic techniques demonstrate differences in the form, number, and laminar distribution of these two afferents in anterior and posterior cingulate cortices. Afferents from the mediodorsal thalamic nucleus terminate in area 24. Most terminals are in layer IIIb, fewer in layer Ia-b, and least in layers V and VI. In contrast, callosal afferents terminate mainly in layers Ib-c, II, IIIa, V, and VI. Thus, thalamic and callosal afferents terminate in a complementary pattern except in layers Ib and IIIb where they overlap. Quantitative analysis of degenerating axon terminals in area 24 indicates that there may be as many as seven times more callosal than mediodorsal thalamic terminals in this cortex. Projections of the anterior thalamic nuclei terminate in areas 29b and 29c, primarily in layer Ia, with fewer in layers Ib-IV and least in layers V and VI. Callosal afferents end mainly in layers V and VI and less densely in layers I-IV, which results in some overlap of thalamic and callosal afferents in layers Ic, IV, and V. In addition, patterns of termination of callosal afferents in posterior cingulate cortex change at borders between previously defined cytoarchitectural areas. Anterior thalamic terminals in area 29c differ from other thalamocortical afferents described previously in that they form two types of terminals. One is large (2-4 micrometer in diameter) and occurs mainly in layer Ia, whereas the second type is smaller and is present in layers Ib-V. Both types of terminals form asymmetric synapses mainly with dendritic spines.

Limbic thalamus in rabbit: architecture, projections to cingulate cortex and distribution of muscarinic acetylcholine, GABAA, and opioid receptors.

Nuclei of the thalamus that project to cingulate cortex have been implicated in responses to noxious stimuli, cholinergic and motor functions. The rabbit limbic thalamus may play an important role in these functions, but has not been studied extensively in terms of its cytoarchitecture, the topographical organization of its cortical projections, and differential transmitter regulation of its subnuclei. Therefore, the architecture, projections to cingulate cortex, and radioligand binding were investigated in the anterior, ventral, lateral, and midline nuclei of rabbit thalamus. The anterior nuclei are highly differentiated because both the dorsal and ventral nuclei have parvicellular and magnocellular divisions. Fluorescent dyes were injected into cingulate cortex to evaluate limbic thalamocortical connections. The anterior medial, submedial, and parafascicular nuclei project primarily to anterior cingulate cortex, while they have small or no projections to posterior areas. The ventral anterior and ventral lateral nuclei have a significant projection to dorsal cingulate cortex, including areas 24b and 29d. Projections of the anterior ventral nucleus are topographically organized, since medial parts of the parvicellular division project to rostral area 29, and lateral parts project to caudal area 29. The lateral nuclei and the parvicellular and magnocellular divisions of the anterior dorsal nucleus project with progressively higher densities in the rostrocaudal plane of area 29. Finally, the magnocellular division of the anterior ventral nucleus projects almost exclusively to caudal and ventral area 29, i.e., granular retrosplenial cortex. Ligand binding studies employed coverslip autoradiography and single grain counting techniques. Muscarinic receptor binding was moderate for both pirenzepine and oxotremorine-M in the parvicellular anterior ventral nucleus, while in other nuclei, there was an inverse relationship in the binding for these ligands. Most notably, the anterior dorsal nucleus, which receives no cholinergic input, had very high oxotremorine-M and low pirenzepine binding, while the anterior medial nucleus, which receives a moderate cholinergic input, had the highest pirenzepine binding and very low oxotremorine-M binding. Muscimol binding to GABAA receptors was highest in the anterior ventral nucleus, while it was at moderate levels in the anterior dorsal and lateral nuclei. The binding of Tyr-D-Ala-Gly-MePhe-Gly-ol to mu opioid receptors and 2-D-penicillamine-5-D-penicillamine-enkephalin to delta opioid receptors were both high in the parvicellular and low in the magnocellular divisions of the anterior dorsal nucleus. The magnocellular division of the anterior ventral, the lateral dorsal, and the parafascicular nuclei had high mu opioid binding, while the lateral dorsal and lateral magnocellular nuclei had low levels of delta opioid binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents.

The cytoarchitecture and thalamic afferents of cingulate cortex were evaluated in the rhesus monkey (Macaca mulatta). Area 24 has three divisions of which area 24a is adjacent to the callosal sulcus and has the least laminar differentiation. Area 24b has more clearly defined layers II, III, and Va, and area 24c, which forms the lower bank of the anterior cingulate sulcus, has a particularly dense layer III. Area 23 also has three divisions, each of which has a distinct layer IV. Area 23a is adjacent to the callosal sulcus and has the thinnest layers II-IV, which have the same cell density as layers V and VI. Area 23b has the largest pyramids in layers IIIc and Va, and area 23c, in the depths of the posterior cingulate sulcus, has the broadest external and thinnest internal pyramidal layers. Finally, areas 29 and 30 are located in the posterior depths of the callosal sulcus. Two divisions of area 29 are apparent: one with a granular layer directly adjacent to layer I (area 29a-c) and another with differentiation of layers III and IV (area 29d). Area 30 has a dysgranular layer IV. Injections of the retrograde tracer horseradish peroxidase (HRP) were made into subdivisions of cingulate cortex in the monkey. Area 25 received thalamic input mainly from the midline parataenial (Pt), central densocellular (Cdc), and reuniens nuclei as well as from the dorsal parvicellular division of the mediodorsal nucleus (MDpc). A less dense projection also originated in the intralaminar parafascicular (Pf), central superior, and limitans (Li) nuclei as well as the medial division of the anterior nuclei (AM). Areas 24a and 24b received most thalamic afferents from fusiform and multipolar cells in the Cdc and Pf nuclei with fewer from the ventral anterior (VA) and MDpc and MD densocellular (MDdc) nuclei and only minor input from AM. Most input to premotor cingulate area 24c appeared to originate in VA, MDdc, and Li. Area 29 received the most dense input from nuclei traditionally associated with limbic cortex including the anteroventral (AV), anterodorsal (AD), and laterodorsal (LD) nuclei. Areas 23a and 23b, in contrast, did not receive AV, AD, or LD input, but the greatest proportion of their thalamic afferents arose in AM. Less-pronounced input also came from the lateroposterior (LP), medial pulvinar, and MDdc nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Spindle neurons of the human anterior cingulate cortex.

The human anterior cingulate cortex is distinguished by the presence of an unusual cell type, a large spindle neuron in layer Vb. This cell has been noted numerous times in the historical literature but has not been studied with modern neuroanatomic techniques. For instance, details regarding the neuronal class to which these cells belong and regarding their precise distribution along both ventrodorsal and anteroposterior axes of the cingulate gyrus are still lacking. In the present study, morphological features and the anatomic distribution of this cell type were studied using computer-assisted mapping and immunocytochemical techniques. Spindle neurons are restricted to the subfields of the anterior cingulate cortex (Brodmann's area 24), exhibiting a greater density in anterior portions of this area than in posterior portions, and tapering off in the transition zone between anterior and posterior cingulate cortex. Furthermore, a majority of the spindle cells at any level is located in subarea 24b on the gyral surface. Immunocytochemical analysis revealed that the neurofilament protein triple was present in a large percentage of these neurons and that they did not contain calcium-binding proteins. Injections of the carbocyanine dye DiI into the cingulum bundle revealed that these cells are projection neurons. Finally, spindle cells were consistently affected in Alzheimer's disease cases, with an overall loss of about 60%. Taken together, these observations indicate that the spindle cells of the human cingulate cortex represent a morphological subpopulation of pyramidal neurons whose restricted distribution may be associated with functionally distinct areas.

Rabbit cingulate cortex: cytoarchitecture, physiological border with visual cortex, and afferent cortical connections of visual, motor, postsubicular, and intracingulate origin.

The connections of cingulate cortex with visual, motor, and parahippocampal cortices in the rabbit brain are evaluated by using a modified Brodmann cytoarchitectural scheme, electrophysiological mapping techniques, and the pathway tracers horseradish peroxidase (HRP) and tritiated amino acids. Rabbit cingulate cortex can be divided into areas 25, 24, and 29. Area 29 is of particular interest because area 29d has a lateral extension with a granular layer IV, area 29b has a caudal extension in which the connections differ from anterior area 29b, and there is a prominent area 29e. Cytoarchitectural delineation of the lateral border of area 29d with area 17 closely approximates the medial edge of the visual field representation in area 17 as determined electrophysiologically. The main interconnections between visual and cingulate cortices occur between cingulate areas 24b and 29d and visual areas 18 and medial parts of area 17. Projections between areas 29d and 18 are organized in a loose topographic fashion with rostral parts of each and caudal parts of each being reciprocally connected. Neurons mainly in superficial layer II-III of areas 17 and 18 project to layer I of area 29d, while the reciprocal projection originates from neurons in layer V of area 29d and project mainly to layer I of areas 17 and 18. The medial portion of motor area 8 projects to areas 18 and 29d and has a smaller projection to area 17. Postsubicular area 48 is reciprocally connected with area 29d, and it also projects to areas 29b and c. The subiculum projects to areas 29a and 29c but only to the anterior two-thirds of area 29b not the posterior one-third. Rostral area 29d receives the most extensive intrinsic cingulate projections including those from all major cytoarchitectural divisions. Interconnections between areas 29d and 29b appear to be topographically organized in the rostrocaudal plane. Area 29c projects more heavily to area 29b than vice versa. Finally area 29d projects mainly to area 24b in anterior cingulate cortex. In conclusion, rostral area 29d has extensive connections with visual areas 17 and 18, motor area 8, and all subdivisions of cingulate cortex. In light of these connections, it may play a pivotal role in associative functions of the rabbit cerebral cortex including visuomotor integration.

Human cingulate cortex: surface features, flat maps, and cytoarchitecture.

The surface morphology and cytoarchitecture of human cingulate cortex was evaluated in the brains of 27 neurologically intact individuals. Variations in surface features included a single cingulate sulcus (CS) with or without segmentation or double parallel sulci with or without segmentation. The single CS was deeper (9.7 +/- 0.81 mm) than in cases with double parallel sulci (7.5 +/- 0.48 mm). There were dimples parallel to the CS in anterior cingulate cortex (ACC) and anastomoses between the CS and the superior CS. Flat maps of the medial cortical surface were made in a two-stage reconstruction process and used to plot areas. The ACC is agranular and has a prominent layer V. Areas 33 and 25 have poor laminar differentiation, and there are three parts of area 24: area 24a adjacent to area 33 and partially within the callosal sulcus has homogeneous layers II and III, area 24b on the gyral surface has the most prominent layer Va of any cingulate area and distinct layers IIIa-b and IIIc, and area 24c in the ventral bank of the CS has thin layers II-III and no differentiation of layer V. There are four caudal divisions of area 24. Areas 24a' and 24b' have a thinner layer Va and layer III is thicker and less dense than in areas 24a and 24b. Area 24c' is caudal to area 24c and has densely packed, large pyramids throughout layer V. Area 24c' g is caudal to area 24c' and has the largest layer Vb pyramidal neurons in cingulate cortex. Area 32 is a cingulofrontal transition cortex with large layer IIIc pyramidal neurons and a dysgranular layer IV. Area 32' is caudal to area 32 and has an indistinct layer IV, larger layer IIIc pyramids, and fewer neurons in layer Va. Posterior cingulate cortex has medial and lateral parts of area 29, a dysgranular area 30, and three divisions of area 23: area 23a has a thin layer IIIc and moderate-sized pyramids in layer Va, area 23b has large and prominent pyramids in layers IIIc and Va, and area 23c has the thinnest layers V and VI in cingulate cortex. Area 31 is the cinguloparietal transition area in the parasplenial lobules and has very large layer IIIc pyramids. Finally, variations in architecture between cases were assessed in neuron perikarya counts in area 23a. There was an age-related decrease in neuron density in layer IV (r = -0.63; ages 45-102), but not in other layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytology of human caudomedial cingulate, retrosplenial, and caudal parahippocampal cortices.

Brodmann showed areas 26, 29, 30, 23, and 31 on the human posterior cingulate gyrus without marking sulcal areas. Histologic studies of retrosplenial areas 29 and 30 identify them on the ventral bank of the cingulate gyrus (CGv), whereas standardized atlases show area 30 on the surface of the caudomedial region. This study evaluates all areas on the CGv and caudomedial region with rigorous cytologic criteria in coronal and oblique sections Nissl stained or immunoreacted for neuron-specific nuclear binding protein and nonphosphorylated neurofilament proteins (NFP-ir). Ectosplenial area 26 has a granular layer with few large pyramidal neurons below. Lateral area 29 (29l) has a dense granular layer II-IV and undifferentiated layers V and VI. Medial area 29 (29m) has a layer III of medium and NFP-ir pyramids and a layer IV with some large, NFP-ir pyramidal neurons that distinguish it from areas 29l, 30, and 27. Although area 29m is primarily on the CGv, a terminal branch can extend onto the caudomedial lobule. Area 30 is dysgranular with a variable thickness layer IV that is interrupted by large NFP-ir neurons in layers IIIc and Va. Although area 30 does not appear on the surface of the caudomedial lobule, a terminal branch can form less that 1% of this gyrus. Area 23a is isocortex with a clear layer IV and large, NFP-ir neurons in layers IIIc and Va. Area 23b is similar to area 23a but with a thicker layer IV, more large neurons in layer Va, and a higher density of NFP-ir neurons in layer III. The caudomedial gyral surface is composed of areas 23a and 23b and a caudal extension of area 31. Although posterior area 27 and the parasubiculum are similar to rostral levels, posterior area 36' differs from rostral area 36. Subregional flat maps show that retrosplenial cortex is on the CGv, most of the surface of caudomedial cortex is areas 23a, 23b, and 31, and the retrosplenial/parahippocampal border is at the ventral edge of the splenium. Thus, Brodmann's map understates the rostral extent of retrosplenial cortex, overstates its caudoventral extent, and abridges the caudomedial extent of area 23.

Neurofilament and calcium-binding proteins in the human cingulate cortex.

Functional imaging studies of the human brain have suggested the involvement of the cingulate gyrus in a wide variety of affective, cognitive, motor, and sensory functions. These studies highlighted the need for detailed anatomic analyses to delineate its many cortical fields more clearly. In the present study, neurofilament protein, and the calcium-binding proteins parvalbumin, calbindin, and calretinin were used as neurochemical markers to study the differences among areas and subareas in the distributions of particular cell types or neuropil staining patterns. The most rostral parts of the anterior cingulate cortex were marked by a lower density of neurofilament protein-containing neurons, which were virtually restricted to layers V and VI. Immunoreactive layer III neurons, in contrast, were sparse in the anterior cingulate cortex, and reached maximal densities in the posterior cingulate cortex. These neurons were more prevalent in dorsal than in ventral portions of the gyrus. Parvalbumin-immunoreactive neurons generally had the same distribution. Calbindin- and calretinin-immunoreactive nonpyramidal neurons had a more uniform distribution along the gyrus. Calbindin-immunoreactive pyramidal neurons were more abundant anteriorly than posteriorly, and a population of calretinin-immunoreactive pyramidal-like neurons in layer V was found largely in the most anterior and ventral portions of the gyrus. Neuropil labeling with parvalbumin and calbindin was most dense in layer III of the anterior cingulate cortex. In addition, parvalbumin-immunoreactive axonal cartridges were most dense in layer V of area 24a. Calretinin immunoreactivity showed less regional specificity, with the exception of areas 29 and 30. These chemoarchitectonic features may represent cellular reflections of functional specializations in distinct domains of the cingulate cortex.

Brain gangliosides in dementia of the Alzheimer type.

Gangliosides GM1, GD1a, GD1b, and GT1b were measured in nine brain regions of five patients, clinically and neuropathologically diagnosed as having dementia of the Alzheimer type (DAT), and of three control patients. Analysis of variance revealed that mean concentrations of all gangliosides analyzed were significantly lower in DAT than in control brains. The areas affected in DAT included the nucleus basalis, and entorhinal, posterior cingulate, visual, and prefrontal cortices. A significant interaction between ganglioside type and brain area indicated unequal ganglioside concentrations. Individual gangliosides had significantly different concentrations in the hippocampal, entorhinal, posterior cingulate, visual, and prefrontal cortices. Analysis of ratios of "a"-ganglioside (GM1 and GD1a) and "b"-ganglioside (GD1b and GT1b) subtypes indicated that DAT preferentially affected "b"-gangliosides. Ganglioside concentrations in nucleus basalis did not correlate with age at disease onset, age at death, or postmortem interval. Changes in gangliosides, observed in this study, were not correlated with classic DAT neuropathology.

Laminar distributions of muscarinic acetylcholine, serotonin, GABA and opioid receptors in human posterior cingulate cortex.

Experimental animal studies have demonstrated a number of receptor localizations on specific cortical afferents and neurons. The present study of human posterior cingulate cortex evaluates the laminar distributions of particular receptors and their likely association with components of the neuropil. Coverslip autoradiographic and single grain counting techniques were used followed by heterogeneity analysis in which the layer of peak binding and an index of heterogeneity were determined for each ligand. The index was calculated by determining specific binding by layer as a percentage of binding in all layers. The differences from an absolutely homogeneous distribution, i.e. 11.1% for each of nine layers, were subtracted and the absolute laminar differences summed to form the index. High indices of over 15 reflected heterogeneous binding patterns in neocortex. The binding of ligands for muscarinic acetylcholine, serotonin, opioid, GABA and beta adrenoceptors was evaluated. Pirenzepine binding peaked in layer II of area 23a but was extremely homogeneous with an index of heterogeneity of 8.9. In contrast, oxotremorine-M binding had a peak in layer IIIc and an index of 16.4, while AF-DX 116 binding peaked in layer IIIa-b and had an index of 30.6. Of the ligands for serotonin uptake and receptor binding paroxetine binding was evenly distributed in layers I-III and had a low index of heterogeneity of 9.8. Ketanserin binding was also homogeneous and, since it had an index of 8.9, this pattern was virtually the same as that for paroxetine. In contrast, serotonin and 8-hydroxy-2-(di-n-propylamino)tetralin binding peaked in layer II and had very high indices of 20.8 and 50.3, respectively, suggesting only a limited association with that of the paroxetine distribution. Finally, there were three layers which contained peaks in binding for ligands for opioid, GABA and beta adrenoceptors. Firstly, layer Ia had peak dynorphin-A binding, the latter of which had an index of 22.6. Secondly, Tyr-D-Ala-Gly-MePhe-Gly-ol and 2-D-penicillamine-5-D-penicillamine-enkephalin binding peaked in layer II and had indices of 8.6 and 17.4, respectively. Thirdly, muscimol and (-)-cyanopindolol binding peaked in layer IIIa-b and had indices of 29.6 and 11.1, respectively. When viewed in the context of experimental animal studies, it is likely that heterogeneities in oxotremorine-M and paroxetine binding are associated with the termination of the thalamic and raphe nuclei, respectively. While serotonin 2 receptors are co-distributed with serotonin uptake sites, serotonin 1A receptors have a significant mismatch with these sites.(ABSTRACT TRUNCATED AT 400 WORDS)