Diversity of spatial relationships of the claustrum and insula in branches of the mammalian radiation

Using digital images of stained sections, we conducted a comparative survey of the visible gross morphology of the insular cortex and the claustrum in 26 mammalian species, representing most of the major mammalian radiations. We observed several features that are conserved in the mammals that we examined, including the absence of expansion of the insular cortex into out-branching lobes, the adherence of the claustrum to the fundus of the rhinal sulcus and to endopiriform cellular regions, and several features that varied, including the colocation of the insular and claustrocortex, the cortical origin of the operculations that cover the insula, the locations of large accumulations of claustral cells, and the presence of thin extensions of groups of claustral cells. We suggest that the final shape of the claustrum is highly influenced by the expansion of two medially adjacent subcortical structures, the striatum and amygdala. We further suggest that the neighboring locations of the claustrum and insula may be due to a dependence of each of these structures upon proximity to olfactory cortex, rather than to any connectional relationships between them.     

第二触觉系统:编码触觉情绪成分的C纤维

过去曾认为,人类触觉信息特异地由大直径有髓(Aβ)神经纤维传导。然而最近的研究表明,哺乳动物皮肤的机械感受器不仅有Aβ纤维分布,还有大量低阈值、低传导速度的小直径无髓(C)神经纤维分布,后者对轻微的非伤害性皮肤变形反应敏感,而对快速的皮肤运动反应微弱。初级传入C纤维投射至脊髓浅层,并与脊髓板层II内的次级感觉神经元形成突触联系,再通过脊髓丘脑束投射至岛叶。功能磁共振(fMRI)研究发现,缓慢移动的触觉刺激可以明显地激活岛叶并引起愉悦感,同时还可以激活眶额叶内与愉悦味觉和嗅觉激活区域邻近的部位。这些反应的性质和所激活的部位说明,C纤维触觉主要与边缘系统的功能有关,编码触觉的情绪成分。     

Effect of Age on Human Brain Serotonin (S-1) Binding Sites

The effect of age on the binding of [3H]5-hydroxytryptamine [( 3H]5-HT, serotonin) to postmortem human frontal cortex, hippocampus, and putamen from individuals between the ages of 19 and 100 years was studied. One high-affinity binding site was observed in adult brains, with a mean KD of 3.7 nM and 3.2 nM for frontal cortex and hippocampus, respectively, and 9.2 nM for putamen. Decreased binding capacities (Bmax) with age were detected in frontal cortex and hippocampus. In putamen a decrease in affinity was noted. Postmortem storage did not significantly contribute to the age-related changes. No significant sex differences were detected. [3H]5-HT binding was also studied in brains from human neonates. The specific binding was 1.5-3 times lower than in adult frontal cortex and putamen, and Scatchard analysis suggested more than one binding site. In infant hippocampus a single binding site was observed and except for a premature individual, the binding capacity approximated adult values.     

Autoradiographic Analysis of [3H]Imipramine Binding in the Human Brain Postmortem: Effects of Age and Alcohol

In vitro quantitative autoradiography of high-affinity [3H]imipramine binding sites was performed on 16 human brains postmortem. The densities of binding sites were highest in the hypothalamus. Next, in descending order, were the basal and lateral nuclei of the amygdala; substantia innominata; insular cortex; the central nucleus of the amygdala; the anterior nucleus of the thalamus; the head of the caudate nucleus; portions of the frontal, parietal, and temporal cortex; claustrum; the granular layer of the dentate gyrus; substantia nigra; the pyramidal layer of CA fields; globus pallidus; red nucleus; and white matter. Imipramine binding was found to increase with age in a region-specific manner. The presence of alcohol had a similar effect, which was most pronounced in the hippocampus. Sex and time from death to autopsy did not affect imipramine binding, in our sample.     

Latexin regulates the abundance of multiple cellular proteins in hematopoietic stem cells

Latexin is the only known carboxypeptidase A inhibitor in mammals and shares structural similarity with cystatin C, suggesting that latexin regulates the abundance of as yet unidentified target proteins. A forward genetic approach revealed that latexin is involved in homeostasis of hematopoietic stem cells (HSCs) in mice; however, little is known about the mechanisms by which latexin negatively affects the numbers of HSCs. In this study, we found that latexin is preferentially expressed in hematopoietic stem/progenitor cells, and is co-localized with the molecules responsible for the interaction of HSCs with a bone marrow niche, such as N-cadherin, Tie2, and Roundabout 4. Latexin-knockout young female mice showed an increase in the numbers of KSL (c-Kit(+)/Sca-1(+)/linegae marker-negative) cells, which may be attributable to enhanced self-renewal because latexin-deficient KSL cells formed more colonies than their wild-type counterparts in methylcellulose culture. Proteomic analysis of Sca-1(+) bone marrow cells demonstrated that latexin ablation reduced the abundance of multiple cellular proteins, including N-cadherin, Tie2, and Roundabout 4. Finally, we found that latexin expression was lost or greatly reduced in approximately 50% of human leukemia/lymphoma cell lines. These results imply that latexin inhibits the self-renewal of HSCs by facilitating the lodgment of HSCs within a bone marrow niche to maintain HSC homeostasis.     

Structural basis of frontal cortex control of thalamic and basal nuclei in dogs

Fibrillar degeneration after extirpation of the frontal cortical field F2, central part, was observed in dogs by Nauta--Gygax and Fink--Heimer's methods. Degenerated fibrillae were stated to form two bundles and terminate near the neurons of nonspecific thalamic nuclei: n. ret, MD, pf, sprf, as well as in the neurons of specific thalamic nuclei: n. Vna, cgl, cgm, pul. Degenerated processes of the frontal cortex cells projected to the neurons of basal nuclei: the head of nucleus caudatus, putamen, globus pallidus. In the claustrum degenerative changes were not observed.     

Insulin, glucagon and somatostatin localization in the pancreas of metamorphosed Xenopus laevis

The current study was designed to determine if insulin, glucagon and somatostatin-containing cells are present in the pancreas of adult Xenopus laevis. Localization methods utilized included cytochemical aldehyde fuchsin (AF) staining as well as the immunochemical peroxidase antiperoxidase (PAP) procedure for light microscopy. The results show numerous large clusters of AF-positive cells within a network of highly vascularized acinar tissue. PAP immunochemical localization with insulin antibody on adjacent sections demonstrates positive immunoreactivity to AF-positive cell groups and also the presence of immunoreactive insulin (IRI). Cells exhibiting this immunoreactivity are located in the central region of the islet-like structures. Serial sections not only show PAP immunoreactivity for IRI, but also for immunoreactive glucagon (IRG) and immunoreactive somatostatin (IRS) in the same islet-like structure. IRG and IRS-containing cells are situated around the periphery of the islet-like structures, surrounding the central core of IRI-containing cells. Antibody specificity was confirmed by homologous and heterologous antigen immuno-absorbance assays, as well as incubation of adjacent sections in preimmune sera. Based on this data we conclude that: the distribution of cells of the endocrine pancreas of metamorphosed Xenopus laevis is similar to that of many mammals and certain urodeles. Given the apparent specificity of the antigen-antibody reactions, it appears that Xenopus insulin, glucagon and somatostatin are structurally conserved.     

Somatosensory evoked potentials following lesions of the claustrum

Ipsi- and contralateral cortical somatosensory evoked potentials (SEP) were recorded following median nerve stimulation in 12 patients with unilateral brain lesions and in 5 healthy subjects. Computed tomographic scans of brain were performed on admission. In all patients with lesions of the claustrum there was absence of SEP contralateral to the side of the lesion and ipsilateral to the stimulated nerve. This phenomenon did not appear in our material following lesions involving other structures e.g. thalamus or somatosensory cortex. Our observations suggest that the claustrum may influence deeply the contralateral somatosensory cortex. This may be due to the fact that a large part of the claustrum is involved in transmission of the sensory information from receptors to the somatosensory cortex.     

Multimodal cross-talk of olfactory and gustatory information in the endopiriform nucleus in rats

The endopiriform nucleus (EPN) is a large group of multipolar cells located in the depth of the piriform cortex (PC). Although many studies have suggested that the EPN plays a role in temporal lobe epilepsy, the normal function of the EPN remains to be elucidated. By using optical imaging of coronal brain slice preparations with voltage-sensitive dye, we found signal propagation from the PC or gustatory cortex (GC) to the EPN in normal medium. In our previous research, we failed to elicit a reliable signal reproducibly in the EPN by single stimulation either to the PC or GC. In our current research, we found that a double-pulse stimulation to either the PC or GC (interpulse interval: 20-100 ms) induced robust signal propagation to the EPN through excitation in the agranular division of the insular cortex (AI), with further extension to the claustrum. Finally, double site paired-pulse stimulation to the PC and GC also evoked excitation in the AI, claustrum, and EPN. These results suggest that the EPN has dual roles: 1) further processing of modality-specific olfactory and gustatory information from the PC and GC, respectively and 2) synergistic integration of PC-derived olfactory information and GC-derived gustatory information.     

Colocalization of neuropeptides and NADPH-diaphorase in the intra-adrenal neuronal cell bodies and fibres of the rat

Colocalization of vasoactive intestinal peptide, neuropeptide Y, calcitonin gene-related peptide, substance P, and tyrosine hydroxylase, respectively, with NADPH-diaphorase staining in rat adrenal gland was investigated using the double labelling technique. All vasoactive intestinal peptide- and some neuropeptide Y-immunoreactive intrinsic neuronal cell bodies seen in the gland were double stained with NADPH-diaphorase. Double labelling also occurred in some nerve fibres immunoreactive to vasoactive intestinal peptide and neuropeptide Y in the medulla and cortex. No colocalization of calcitonin gene-related peptide, substance P or tyrosine hydroxylase immunoreactivity with NADPH-diaphorase staining was observed. However, nerve fibres with varicosities immunoreactive for all the neuropeptides examined were closely associated with some of the NADPH-diaphorase-stained neuronal cell bodies. Thus, in rat adrenal gland, nitric oxide is synthesized in all ganglion cells containing vasoactive intestinal peptide and in some containing neuropeptide Y, but not in those containing calcitonin gene-related peptide, substance P or tyrosine hydroxylase.     

Senile plaques in an aged western lowland gorilla.

Senile plaques (SPs) were found in the cerebral cortex of a 44-year-old Western lowland gorilla (Gorilla gorilla gorilla). All the SPs were obtained as dense assemblies consisting of fibrous materials by silver impregnation, but were not detected by Congo red. More SPs were detected by immunostaining for amyloid beta protein (A beta) and a half of A beta-positive-SPs were also immunoreactive for apolipoprotein E. Moreover, all SPs were immunoreactive for A beta 42 and A beta 43, but not for A beta 40. SPs also did not contain A beta precursor protein-positive structures. These findings suggested that SPs in this case were diffuse plaques. To our knowledge, this is the first report of SPs in the gorilla.     

Distribution of neurotensin-like immunoreactivity in the central nervous system of the Formosan monkey

The distribution of neurotensin-like immunoreactivity was investigated in the central nervous system of the Formosan monkey employing immunohistochemical techniques. Neurotensin-containing cells were found to be widely distributed in the forebrain. The principal densities of neurotensin-like neuronal perikarya were located in the limbic system, the basal ganglion and the cerebral cortex; particularly in the amygdala, the septum, the neostriatum, the claustrum and the insula. The stria terminalis and the preoptic area were also rich in immunostained neurotensin-like neurons. A large number of immunoreactive fibers were observed from the cerebral cortex to the spinal cord in locations such as the median eminence, the arcuate nucleus, the hippocampus, the central gray and the dorsal horn of the spinal cord. We analyzed in detail the distribution of neurotensin-like immunoreactivity in the brain of the Formosan monkey, and compared these results with those obtained in the brain of the rat, Japanese monkey and human. Some possible implications regarding differences in location of this peptide are also briefly discussed.     

Functional organization of auditory cortical fields in the mongolian gerbil (Meriones unguiculatus): Binaural 2-deoxyglucose patterns

Summary Unilaterally deafened (cochlear destruction) gerbils were exposed to white noise after injection of 14-C-2-deoxyglucose. The labelling patterns were compared to those of unstimulated operated animals, noise stimulated control animals and bilaterally ear plugged animals.Serial transverse, horizontal and tangential autoradiographs through the cortex were analysed. In lesioned animals, labelling was strongly reduced on the side contralateral to the lesion in the high frequency regions of A1 and the anterior auditory field (AAF). We assume that these regions correspond to the high frequency EI cell areas. Fine banding could be seen superimposed on this pattern in transverse and tangential sections. We suggest that this may be due to alternating strips of EI and EE cells orthogonal to iso-frequency contours. In the low frequency regions of A1 and AAF, labelling asymmetries were also present, but were less pronounced. We assume that these effects are due to low frequency EE cells.In sub-cortical structures, labelling was reduced in the inferior colliculus and ventral part of the medial geniculate body contralateral to the lesioned ear, but no labelling pattern was visible. We presume that the spatial separation of EE and EI inputs to these structures is not marked enough to allow labelling patterns to be seen. In the superior olivary complex, labelling was reduced on the side contralateral to the lesioned ear in the medial dendritic field of the medial superior olivary nucleus and in the nucleus of the trapezoid body. Ipsilateral to the lesioned ear, labelling was reduced in the lateral dendritic field of the medial superior olive.     

Mice with deficiency of G protein gamma3 are lean and have seizures

Emerging evidence suggests that the gamma subunit composition of an individual G protein contributes to the specificity of the hundreds of known receptor signaling pathways. Among the twelve gamma subtypes, gamma3 is abundantly and widely expressed in the brain. To identify specific functions and associations for gamma3, a gene-targeting approach was used to produce mice lacking the Gng3 gene (Gng3-/-). Confirming the efficacy and specificity of gene targeting, Gng3-/- mice show no detectable expression of the Gng3 gene, but expression of the divergently transcribed Bscl2 gene is not affected. Suggesting unique roles for gamma3 in the brain, Gng3-/- mice display increased susceptibility to seizures, reduced body weights, and decreased adiposity compared to their wild-type littermates. Predicting possible associations for gamma3, these phenotypic changes are associated with significant reductions in beta2 and alphai3 subunit levels in certain regions of the brain. The finding that the Gng3-/- mice and the previously reported Gng7-/- mice display distinct phenotypes and different alphabetagamma subunit associations supports the notion that even closely related gamma subtypes, such as gamma3 and gamma7, perform unique functions in the context of the organism.     

Modality-specific neural effects of selective attention to taste and odor

The insular cortex is implicated in general attention and in taste perception. The effect of selective attention to taste on insular responses may therefore reflect a general effect of attention or it may be (taste) modality specific. To distinguish between these 2 possibilities, we used functional magnetic resonance imaging to evaluate brain response to tastes and odors while subjects passively sampled the stimuli or performed a detection task. We found that trying to detect a taste (attention to taste) resulted in activation of the primary taste cortex (anterior and mid-dorsal insula) but not in the primary olfactory cortex (piriform). In contrast, trying to detect an odor (attention to odor) increased activity in primary olfactory but not primary gustatory cortex. However, we did identify a region of far anterior insular cortex that responded to both taste and odor "searches." These results demonstrate modality-specific activation of primary taste cortex by attention to taste and primary olfactory cortex by attention to odor and rule out the possibility that either response reflects a general effect of attentional deployment. The findings also support the existence of a multimodal region in far anterior insular cortex that is sensitive to directed attention to taste and smell.     

Subcellular localization of immunoreactive oxytocin within thymic epithelial cells of the male mouse

Immunoreactive oxytocin is expressed by thymic epithelial cells, which share properties with neuroendocrine cells. In order to investigate the assumed paracrine secretion of oxytocin, we studied the subcellular localization of immunoreactive oxytocin within thymic tissue and cultured thymic epithelial cells of the male mouse. Three types of immunoreactive cells were distinguished with the electron microscope. Immunoreactive oxytocin was found to be restricted to the cytoplasm by the use of pre- and postembedding methods. Some epithelial cells, especially in the cortex, showed a pronounced labelling of vesicular membranes and membrane tubules of the endoplasmic reticulum. In some cells, keratin filaments were associated with the electrondense stain. Under culture conditions immunoreactive cells of different shapes were found, all displaying similar patterns of labelling. The contents of different types of vacuoles were only rarely labelled. A special class of immunoreactive exocytotic vesicles could not be identified. Thus, our results do not support neuroendocrine secretion of oxytocin via vesicles of thymic epithelial cells but offer alternative modes of secretion.     

Aberrant Resting-State Corticostriatal Functional Connectivity in Cirrhotic Patients with Hyperintense Globus Pallidus on T1-Weighted MR Imaging

Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP) on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting-state brain dysfunction in real time.     

Detection of the neurospecific protein Sy-1 in the human brain and its regional localization in nerve tissue

Using affinity chromatography, a neurospecific protein was isolated from human and rat brain. Both proteins were shown to possess identical physico-chemical properties. However, antisera raised against these proteins exhibited no cross reactions with the corresponding proteins, thus suggesting their species specificity. Immunochemical analysis revealed that the neurospecific protein from rat brain is identical to protein Sy-1 specific for rat brain. Since the human brain protein is analogous to its rat brain counterpart, it may also be considered as protein Sy-1. The uneven distribution of the protein in various structures of human brain was demonstrated by the immunoenzymatic method. Protein Sy-1 is found at relatively low concentrations in the cortex, caudate nucleus and claustrum (2.5-5 micrograms/mg of water-soluble protein), but is predominant in the brain stem (20 micrograms/mg).     

In Vivo Release from Cerebral Cortex of [14C]Glutamate Synthesized from [U-14C]Glutamine

Awake, unrestrained, and behaviourally normal animals with superfusion cannulae implanted over the sensorimotor cortex were used in a study of the capacity of infused [U-14C]glutamine for labelling glutamate and other amino acids released by depolarising stimuli. A spontaneous background release of [14C]glutamate was detected. This was increased by tityustoxin (1 microM). The specific radioactivity of glutamate increased eightfold during the evoked-release period. [14C]Aspartate was also detected and showed increased release, but not increased specific labelling, in response to depolarisation. Evoked gamma-aminobutyric acid (GABA) release occurred but only small amounts of [14C]GABA were detected. Glutamine showed increased rates of uptake to the sensorimotor cortex during stimulation periods, suggesting an accelerated breakdown via glutaminase.