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)

Human posterior cingulate cortex (PCC) and retrosplenial cortex (RSC) form the posterior cingulate gyrus, however, monkey connection and human imaging studies suggest that PCC area 23 is not uniform and atlases mislocate RSC. We histologically assessed these regions in 6 postmortem cases, plotted a flat map, and characterized differences in dorsal (d) and ventral (v) area 23. Subsequently, functional connectivity of histologically guided regions of interest (ROI) were assessed in 163 [ 18 F] fluorodeoxyglucose human cases with PET. Compared to area d23, area v23 had a higher density and larger pyramids in layers II, IIIc, and Vb and more intermediate neurofilament-expressing neurons in layer Va. Coregisrtration of each case to standard coordinates showed that the ventral branch of the splenial sulci coincided with the border between d/v PCC at −5.4±0.17 cm from the vertical plane and +1.97±0.08 cm from the bi-commissural line. Correlation analysis of glucose metabolism using histologically guided ROIs suggested important circuit differences including dorsal and ventral visual stream inputs, interactions between the vPCC and subgenual cingulate cortex, and preferential relations between dPCC and the cingulate motor region. The RSC, in contrast, had restricted correlated activity with pericallosal cortex and thalamus. Visual information may be processed with an orbitofrontal link for synthesis of signals to drive premotor activity through dPCC. Review of the literature in terms of a PCC duality suggests that interactions of dPCC, including area 23d, orients the body in space via the cingulate motor areas, while vPCC interacts with subgenual cortex to process self-relevant emotional and non-emotional information and objects and self reflection.

No abstract

Chronic treatment of rats with ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC) results in tolerance to its acute behavioral effects. In a previous study, 21-day ⌬ 9 -THC treatment in rats decreased cannabinoid activation of G proteins in brain, as measured by in vitro autoradiography of guanosine-5Ј

Human functional imaging and neurocytology have produced important revisions to the organization of the cingulate gyrus and demonstrate four structure/function regions: anterior, midcingulate (MCC), posterior (PCC), and retrosplenial. This study evaluates the brain of a rhesus and 11 cynomolgus monkeys with Nissl staining and immunohistochemistry for neuron-specific nuclear binding protein, intermediate neurofilament proteins, and parvalbumin. The MCC region was identified along with its two subdivisions (a24′ and p24′). The transition between areas 24 and 23 does not involve a simple increase in the number of neurons in layer IV, but includes an increase in neuron density in layer Va of p24′, a dysgranular layer IV in area 23d, granular area 23 with a neuron dense layer Va and area 31. Each area on the dorsal bank of the cingulate gyrus has an extension around the fundus of the cingulate sulcus (f 24c, f 24c′, f 24d, f 23c), while most cortex on the dorsal bank is comprised of frontal motor areas. The PCC is comprised of a dysgranular area 23d, area 23c in the caudal cingulate sulcus, a dorsal cingulate gyral area 23a/b and a ventral area 23a/b. Finally, a dysgranular transition zone includes both area 23d and retrosplenial area 30. The distribution of areas was plotted onto flat maps to show the extent of each and their relationships to the vertical plane at the anterior commissure, corpus callosum, and cingulate sulcus. This major revision of the architectural organization of monkey cingulate cortex provides a new context for connection studies and for devising models of neuron diseases. Keywords cingulate cortex; neurofilament proteins; cingulate motor areas; midcingulate cortex; retrosplenial cortex; pyramidal neurons The primate cingulate gyrus was early considered to be a uniform structure with a role in limbic function (Broca, 1878;Papez, 1937;MacLean, 1990). Although it has also been recognized to have a dual structure with different connections (Baleydier and Mauguiere, 1980; and with an executive function in the anterior and evaluative role for the posterior parts (Vogt et al., 1992), many cytoarchitectural studies showed the human cingulate gyrus to be more complex than the dual model suggests (Smith, 1907;Brodmann, 1909;Vogt and Vogt, 1919; von Economo and Koskinas, 1925;Rose, 1927) and numerous human functional imaging studies show that cingulate cortex is involved in more than just two essential functions. Structure/function correlations with human neurocytology and imaging, electrical stimulation NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript and stroke findings suggest there are four rather than just two regions (Vogt et al., , 2004. The four regions are perigenual anterior cingulate cortex (ACC), midcingulate cortex (MCC), posterior cingulate cortex (PCC), and retrosplenial cortex (RSC).A key aspect of the four-region model is division of Brodmann's (1909) ACC into a perigenual and midcingulate regions and this differentiation is pivotal to understanding the ...

In previous studies from our laboratory, chronic noncontingent morphine administration decreased μ opioid receptor-activated G-proteins in specific brainstem nuclei. In the present study, μ opioid receptor binding and receptor-activated G-proteins were examined after chronic heroin self-administration. Rats were trained to self-administer intravenous heroin for up to 39 d, achieving heroin intake up to 366 mg · kg−1 · d−1. μ opioid-stimulated [35S]GTPγS and [3H]naloxone autoradiography were performed in adjacent brain sections. Agonist-stimulated [35S]GTPγS autoradiography also examined other G-protein-coupled receptors, including δ opioid, ORL-1, GABAB, adenosine A1, cannabinoid, and 5-HT1A. In brains from heroin self-administering rats, decreased μ opioid-stimulated [35S]GTPγS binding was observed in periaqueductal gray, locus coeruleus, lateral parabrachial nucleus, and commissural nucleus tractus solitarius, as previously observed in chronic morphine-treated animals. In addition, decreased μ opioid-stimulated [35S]GTPγS binding was found in thalamus and amygdala after heroin self-administration. Despite this decrease in μ-activated G-proteins, [3H]naloxone binding demonstrated increased μ opioid receptor binding in several brain regions after heroin self-administration, and there was a significant decrease in μ receptor G-protein efficiency as expressed as a ratio between agonist-activated G-proteins and μ receptor binding. No effects on agonist-stimulated [35S]GTPγS binding were found for any other receptor examined. The effect of chronic heroin self-administration to decrease μ-stimulated [35S]GTPγS binding varied between regions and was highest in brainstem and lowest in the cortex and striatum. These results not only provide potential neuronal mechanisms that may contribute to opioid tolerance and dependence, but also may explain why various chronic effects of opioids develop to different degrees.

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.

Homologizing between human and nonhuman area 32 has been impaired since Brodmann said he could not homologize with certainty human area 32 to a specific cortical domain in other species. Human area 32 has four divisions, however, and two can be structurally homologized to nonhuman species with cytoarchitecture and receptor architecture: pregenual (p32) and subgenual (s32) in human and macaque monkey and areas d32 and v32 in rat and mouse. Cytoarchitecture showed that areas d32/p32 have a dysgranular layer IV in all species and that areas v32/s32 have large and dense neurons in layer V, whereas a layer IV is not present in area v32. Areas v32/s32 have the largest neurons in layer Va. Features unique to humans include large layer IIIc pyramids in both divisions, sparse layer Vb in area p32, and elongated neurons in layer VI, with area s32 having the largest layer Va neurons. Receptor fingerprints of both subdivisions of area 32 differed between species in size and shape, although AMPA/GABAA and NMDA/GABAA ratios were comparable among humans, monkeys, and rats and were significantly lower than in mice. Layers I-III of primate and rodent area 32 subdivisions share more similarities in their receptor densities than layers IV-VI. Monkey and human subdivisions of area 32 are more similar to each other than to rat and mouse subdivisions. In combination with intracingulate connections, the location, cytoarchitecture, and ligand binding studies demonstrate critical homologies among the four species.