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PubMed1999

Calcium-binding proteins in the dorsal ventricular ridge of the lizard Psammodromus algirus.

The aim of the present work was to study further the intrinsic organization of the dorsal ventricular ridge of lizards. For that purpose, the morphology and distribution of cells and fibers containing the calcium-binding proteins calbindin-D28k, parvalbumin, and calretinin were investigated by using immunohistochemical methods. Colocalization of calcium-binding proteins with the neurotransmitter gamma-aminobutyric acid (GABA) was also studied because they are shown to coexist in many areas of the telencephalon where they define distinct subpopulations of GABAergic local circuit neurons. Neurons containing calcium-binding proteins are limited to the anterior part of the dorsal ventricular ridge (ADVR), whereas the posterior or caudal portion of the ridge is devoid of immunoreactive cells. This result gives further evidence for defining both regions of the dorsal ventricular ridge. Calcium-binding proteins mark three distinct populations of neurons within the ADVR. Two of them, parvalbumin- and calretinin-expressing cells, are GABAergic. On the other hand, calbindin-containing neurons do not express GABA, and the possibility is discussed that these cells are projection neurons. The distribution and overall density of fibers immunoreactive to calcium-binding proteins suggests that most fibers are of extrinsic origin, the thalamic nuclei projecting to the ADVR and the lateral amygdala being good candidates for their origin. The comparison of data on the populations of calcium-binding protein-containing neurons in the reptilian ADVR with those of mammals illustrate the difficulty in finding a mammalian homologue for this controversial region of the reptilian telencephalon.

Animals↗
PubMed1999

Coexpression of neurocalcin with other calcium-binding proteins in the rat main olfactory bulb.

The distribution patterns of four calcium-binding proteins (CaBPs)-calbindin D-28k (CB), calretinin (CR), neurocalcin (NC), and parvalbumin (PV)-in the rat main olfactory bulb were compared, and the degrees ofcolocalization of NC with the other CaBPs were determined by using double immunocytochemical techniques. All investigated CaBPs were detected in groups of periglomerular cells and Van Gehuchten cells, whereas other cell types expressed some of the investigated proteins but not all four. Double-labeling techniques demonstrated the colocalization of NC with CB, CR, or PV in periglomerular cells, whereas each neurochemical group constituted entirely segregated populations in the remaining neuronal types. This is evident in granule cells that demonstrated large but segregated populations immunoreactive to either NC or CR. This study provides a further biochemical characterization of interneuronal types in the rat main olfactory bulb. On the basis of the distinct calcium-binding affinities, each neurochemically defined population may have different responses to calcium influx that would result in the existence of distinct functional subgroups within morphologically defined neuronal types. The expression of the investigated CaBPs in periglomerular cells with both single and colocalized patterns suggests that the local circuits in the glomerular layer are constituted by a complex network of elements with particular calcium requirements.

Animals↗
PubMed1999

Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey.

Immunocytochemical techniques were used to examine the distribution of double-bouquet cells and chandelier cells that were immunoreactive (-ir) for the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV) in the primary visual area (V1), the second visual area (V2), and cytoarchitectonic area TE in the macaque monkey. Furthermore, the connections between CB-, CR-, and PV-ir neurons in these visual areas were investigated at the light microscope level by using a dual-immunocytochemical staining procedure. The most significant findings were three-fold. First, the number and distribution of CB-ir and CR-ir double-bouquet cells and PV-ir chandelier cells differed considerably between different visual areas. In particular, the different distribution of double-bouquet cells was illustrated dramatically at the V1/V2 border, where CB-ir double-bouquet axons were very few or lacking in V1 but were very numerous in V2. Furthermore, PV-ir chandelier cell terminals were relatively sparse in V1, more frequent in V2, and most frequent in area TE. Second, the percentage of CB-, CR-, and PV-ir neurons receiving multiple contacts on their somata and proximal dendrites from other calcium-binding protein neurons varied between 22% and 85%. The highest percentage of contacts found between immunolabelled cells and multiterminals were for the combinations CR/CB (76-85%; percent of cells immunoreactive for CB that were innervated by multiterminals immunoreactive for CR), followed by the combination PV/CR (42-48%), and then by the other combinations that had similar percentages (22-32% for CR/PV; 26-37% for CB/CR; 29-42% for CR/PV). Third, differences in the relative proportions of CB, CR, and PV terminals in contact with CB-, CR-, and PV-ir neurons were consistent between the different cortical areas studied. Thus, certain characteristics of intraareal circuits differ, whereas others remain similar, in different areas of the occipitotemporal visual pathway. The differences may represent regional specializations related to the different processing of visual stimuli, whereas the similarities may be attributed to general functional requisites for interneuronal circuitry.

Animals↗
PubMed2000

Segregation of serotonin 5-HT2A and 5-HT3 receptors in inhibitory circuits of the primate cerebral cortex.

An emerging concept of cortical network organization is that distinct segments of the pyramidal neuron tree are controlled by functionally diverse inhibitory microcircuits. We compared the expression of two serotonin receptor subtypes, the G-protein-coupled 5-hydroxytryptamine2A receptors and the ion-channel gating 5-HT3 receptors, in cortical neuron types, which control these microcircuits. Here we show, using light and electron microscopic immunocytochemical techniques, that 5-HT2A receptors are segregated from 5-HT3 receptors in the macaque cerebral cortex. 5-HT2A receptor immunolabel was found in pyramidal cells and also in GABAergic interneurons known to specialize in the perisomatic inhibition of pyramidal cells: large and medium-size parvalbumin- and calbindin-containing interneurons. In contrast, 5-HT3 label was only present in small GABA-, substance P receptor-, and calbindin-containing neurons and in medium-size calretinin-containing neurons: interneurons known to preferentially target the dendrites of pyramidal cells. This cellular segregation indicates a serotonin-receptor-specific segmentation of the GABAergic inhibitory actions along the pyramidal neuron tree.

Animals↗
PubMed1999

Differential expression of calbindin and calretinin in the human fetal amygdala.

The distribution patterns of the calcium-binding proteins calbindin and calretinin, both expressed early during development within the various amygdaloid nuclei and areas, have been investigated. Anti-calbindin as well as anti-calretinin mark immature, partly migrating neurons in the 5th gestational month; the number of calretinin-immunoreactive neurons is distinctly higher. In the 8th month, calbindin and calretinin are found in a small proportion of presumed pyramidal cells and in various types of non-pyramidal neurons. Small and large bipolar and small and large multipolar neurons are shown to express calbindin and calretinin. Double-labellings show that calbindin and calretinin are largely contained in different subsets of these neuronal types, which are considered to represent interneurons. These nerve cell classes are widespread within the amygdala with mainly moderate to high packing densities. Diffuse immunoreactive structures, which are found in different intensities in the various amygdaloid nuclei, display distinct redistribution during fetal development. The results show that during early fetal development calbindin and particularly calretinin may be involved in the regulation of neuronal migration. In later development, definite subsets of interneurons, which are likely to be functionally different, are marked by anti-calbindin and -calretinin. Different diffuse immunolabelling at various developmental stages probably indicates the sequential arrival of afferent input from brain areas containing calbindin- or calretinin-immunoreactive nerve cells. With the exception that calretinin may be transiently expressed in pyramidal neurons, the distribution of calbindin- and calretinin-immunoreactive structures to a large degree corresponds to that in the adult. Thus, little reorganisation is to be expected during proceeding development.

Amygdala↗
PubMed1996

Parvalbumin, calbindin, and calretinin mark distinct pathways during development of monkey dorsal lateral geniculate nucleus.

Immunocyochemical labeling was applied to follow the developmental changes in the calcium-binding proteins parvalbumin (PV), calbindin D28k (CaB), and calretinin (CaR) during fetal and infant development of Macaca monkey dorsal lateral geniculate nucleus (LGN). For all three proteins, LGN cell body and retinal ganglion cell (RGC) axon labeling patterns changed temporally and spatially over development, and many of these were LGN laminar specific. CaR+ and CaB+ cells were present at the youngest age studied, fetal day 55 (F55). After lamination of the LGN occurred between F90 and F115, CaR+ and CaB+ neurons were specific markers for the S, intercalated, and interlaminar layers. Double label immunocytochemistry showed that all CaR+ cells contained CaB, and none contained GABA. CaR+ cell bodies decreased in number soon after birth so that adult LGN contained only a very small number of CaR+ cells. These patterns and cell counts indicated that a downregulation of CaR had occurred in the CaB+ population. Although CaB+ cell density in S and interlaminar zones declined in the adult, cell counts indicated that this is due to dilution of a stable population into a much larger nucleus during development. PV+ cells appeared at F85 only within the putative magnocellular (M) and parvocellular (P) layers, and PV remained a marker for these layers throughout development. Fetal PV cells also contained GABA, indicating that they were LGN interneurons. After birth, GABA-/PV+ cell numbers increased dramatically throughout the whole nucleus so that by the end of the first year, P and M layers were filled with PV+ cells. Their number and size indicated that these were the LGN projection neurons. Beginning at F66, bundles of PV+ axons occupied the anterior-middle LGN and filled the optic tract. Up to F101, PV+ synaptic terminals were restricted to Players, but after F132 labeling in M layers was heavier than in P layers. Axonal labeling for CaR began at F125. Prenatally CaR+ terminals were present mainly in P layers, whereas by postnatal 9 weeks labeling in M layers much exceeded P layers. Axonal labeling for CaB was present at F132, but CaB+ terminals were observed only after birth with labeling always heavier in M than P layers. By postnatal 9 weeks, PV, CaR, and CaB were colocalized in the same axons and terminals. These experiments indicated that during development and in the adult LGN, both CaR and CaB were markers for the LGN neurons in the S and intercalated pathway. CaR was present transiently while CaB persisted into adulthood. PV was a M and P layer marker first for interneurons and later for projection cells. The complex temporal developmental patterns found in this study suggested that viewing PV, CaB, and CaR simply as calcium-buffering proteins severely underestimates their functional roles during visual system maturation.

Age Factors↗
PubMed1999

Calcium-binding proteins: differential expression in the rat olfactory cortex after neonatal olfactory bulbectomy.

Calbindin, parvalbumin, and calretinin, members of EF-hand calcium-binding proteins, play important roles in buffering intracellular calcium ions. These proteins are localized in distinct populations of cells in the olfactory bulb (the primary sensory relay in the olfactory system) and its major synaptic target, the primary olfactory cortex (POC). In the present study, the postnatal expression of these calcium-binding proteins in layer III of POC was quantitatively examined 30 days after neonatal bulbectomy, a manipulation known to cause cell death and neurotransmitter changes. The numbers of both calbindin and parvalbumin-immunoreactive profiles showed significant increases (68% and 163%, respectively), while calretinin-immunoreactive profiles exhibited a 46% reduction. The data demonstrate that the expression of these calcium-binding proteins is regulated in part by the afferent input from the olfactory bulb. Furthermore, the resultant increase in calbindin and parvalbumin expression may provide neuroprotective support necessitated by possible alterations in intracellular calcium ions and other neurochemical factors that accompany neonatal bulb removal.

Animals↗
PubMed1998

Chemical phenotype of calretinin interneurons in the human striatum.

We recently reported the existence of a new class of aspiny interneurons characterized by their immunoreactivity for the calcium-binding protein calretinin (CR) in human striatum. This group is composed of numerous medium-sized (10-20 microm) neurons with poorly branched dendrites and a smaller number of large-sized (24-42 microm) neurons with highly ramified dendrites. We further demonstrated the selective sparing of the medium-sized, but not all the large-sized, CR+ striatal neurons in Huntington's disease. In the present study, we applied a double-antigen localization method to postmortem striatal tissue obtained from normal individuals to further characterize the chemical phenotype of these two subsets of CR+ neurons. Our results reveal that in the medium-sized neurons, CR is not colocalized with any of the following current markers of striatal neurons: calbindin, parvalbumin, beta-nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), or choline acetyltransferase (ChAT). Furthermore, quantitative estimates show that the medium-sized CR+ neurons are by far the most abundant type of interneurons in the human striatum. In contrast, CR is colocalized with ChAT in about 80% of the large-sized CR+ neurons. Thus, the medium-sized CR+ neurons appear to form a distinct class of striatal interneurons, whereas most of the large-sized CR+ neurons belong to the population of giant cholinergic neurons. This study has provided the first exhaustive characterization of the chemical phenotype of the CR + neurons in the human striatum.

Adult↗
PubMed2001

Structure of longitudinal brain zones that provide the origin for the substantia nigra and ventral tegmental area in human embryos, as revealed by cytoarchitecture and tyrosine hydroxylase, calretinin, calbindin, and GABA immunoreactions.

In a previous work, mapping early tyrosine hydroxylase (TH) expressing primordia in human embryos, the tegmental origin of the substantia nigra (SN) and ventral tegmental area (VTA) was located across several neuromeric domains: prosomeres 1-3, midbrain, and isthmus (Puelles and Verney, [1998] J. Comp. Neurol. 394:283-308). The present study examines in detail the architecture of the neural wall along this tegmental continuum in 6-7 week human embryos, to better define the development of the SN and VTA. TH-immunoreactive (TH-IR) structures were mapped relative to longitudinal subdivisions (floor plate, basal plate, alar plate), as well as to radially superposed strata of the neural wall (periventricular, intermediate, and superficial strata). These morphologic entities were delineated at each relevant segmental level by using Nissl-stained sections and immunocytochemical mapping of calbindin, calretinin, and GABA in adjacent sagittal or frontal sections. A numerous and varied neuronal population originates in the floor plate area, and some of its derivatives become related through lateral tangential migration with other neuronal populations born in distinct medial and lateral portions of the basal plate and in a transition zone at the border with the alar plate. Some structural differences characterize each segmental domain within this common schema. The TH-IR neuroblasts arise predominantly within the ventricular zone of the floor plate and, more sparsely, within the adjacent medial part of the basal plate. They first migrate radially from the ventricular zone to the pia and then apparently move laterally and slightly rostralward, crossing the superficial stratum of the basal plate. Several GABA-IR cell populations are present in this region. One of them, which might represent the anlage of the SN pars reticulata, is generated in the lateral part of the basal plate.

Age Factors↗
PubMed2000

Distribution of parvalbumin, calretinin, and calbindin-D(28k) immunoreactivity in the rat amygdaloid complex and colocalization with gamma-aminobutyric acid.

To understand the organization of inhibitory circuitries in the rat amygdala, the distribution of parvalbumin, calretinin, and calbindin immunoreactivity was investigated in the rat amygdaloid complex. Colocalization of various calcium-binding proteins with the inhibitory transmitter gamma-aminobutyric acid (GABA) was studied by using the mirror technique. Parvalbumin-immunoreactive (-ir) elements were located mostly in the deep amygdaloid nuclei, whereas the calretinin-ir and calbindin-ir staining were most intense in the cortical nuclei as well as in the central nucleus and the amygdalohippocampal area. Second, the distribution of immunopositive neurons largely parallelled the distribution of terminal and neuropil labeling. Third, immunostained neurons could be divided into four major morphologic types (types 1-4) based on the characteristics of the somata and the dendritic trees. The fourth lightly stained neuronal type that had a pyramidal GABA-negative soma was observed only in calretinin and calbindin preparations. Fourth, parvalbumin-ir terminals formed basket-like plexus and cartridges, which suggests that parvalbumin labels GABAergic inhibitory basket cells and axo-axonic chandelier cells, respectively. Colocalization studies indicated that 521 of 553 (94%) of parvalbumin-ir, 419 of 557 (75%) of calbindin-ir, and 158 of 657 (24%) of calretinin-ir neurons were GABA-positive in the deep amygdaloid nuclei. A high density of large GABA-negative calbindin-ir neurons was observed caudally in the medial division of the lateral nucleus and GABA-negative calretinin-ir neurons were observed in the magnocellular division of the accessory basal nucleus as well as in the intermediate and parvicellular divisions of the basal nucleus. These data suggest that in various amygdaloid areas, neuronal excitability is controlled by GABAergic neurons that contain different calcium-binding proteins. The appearance of basket-like plexus and cartridges in the parvalbumin preparations, but not in calretinin preparations, suggests that like in the hippocampus, the distribution of inhibitory terminals in the dendritic and perisomatic regions of postsynaptic neurons in the rat amygdala is organized in a topographic manner.

Amygdala↗
PubMed2000

Expression of calcium-binding proteins in the diencephalon of the lizard Psammodromus algirus.

This work is a study of the distribution pattern of calbindin-D28k, calretinin, and parvalbumin in the diencephalic alar plate of a reptile, the lizard Psammodromus algirus, by using the prosomeric model (Puelles [1995] Brain Behav Evol 46:319-337), which divides the alar plate of the diencephalon into the caudorostrally arranged pretectum (p1), dorsal thalamus plus epithalamus (p2), and ventral thalamus (p3). Calbindin and calretinin are more extensively expressed in the dorsal thalamus than in the neighboring alar regions, and therefore these calcium-binding proteins are particularly suitable markers for delimiting the dorsal thalamus/epithalamus complex from the ventral thalamus and the pretectum. Conversely, parvalbumin is more intensely expressed in the pretectum and ventral thalamus than in the dorsal thalamus/epithalamus complex. Within the dorsal thalamus, calcium-binding protein immunoreactivity reveals a three-tiered division. The pretectum displays the most intense expression of parvalbumin within the diencephalon. Virtually all nuclei in the three sectors of the pretectum (commissural, juxtacommissural, and precommissural) present strong to moderate expression of parvalbumin. We compare the distribution of calcium-binding proteins in the diencephalon of Psammodromus with other vertebrates, with mammals in particular, and suggest that the middle and ventral tiers of the reptilian dorsal thalamus may be comparable to nonspecific or plurimodal posterior/intralaminar thalamic nuclei in mammals, on the basis of the calcium-binding protein expression patterns, as well as the hodological and embryological data in the literature.

Animals↗
PubMed2000

Early loss of interneurons and delayed subunit-specific changes in GABA(A)-receptor expression in a mouse model of mesial temporal lobe epilepsy.

Unilateral injection of kainic acid (KA) into the dorsal hippocampus of adult mice induces spontaneous recurrent partial seizures and replicates histopathological changes observed in human mesial temporal lobe epilepsy (MTLE) (Bouilleret V et al., Neuroscience 1999; 89:717-729). Alterations in pre- and postsynaptic components of GABAergic neurotransmission were investigated immunohistochemically at different time points (1-120 days) in this mouse model of MTLE. Markers of GABAergic interneurons (parvalbumin, calbindin-D28k, and calretinin), the type-1 GABA transporter (GAT1), and major GABA(A)-receptor subunits expressed in the hippocampal formation were analyzed. Acutely, KA injection produced a profound loss of hilar cells but only limited damage to CA1 and CA3 pyramidal cells. In addition, parvalbumin and calbindin-D28k staining of interneurons disappeared irreversibly in CA1 and dentate gyrus (DG), whereas calretinin staining was spared. The prominent GABA(A)-receptor alpha1 subunit staining of interneurons also disappeared after KA treatment, suggesting acute degeneration of these cells. Likewise, GAT1 immunoreactivity revealed degenerating terminals at 24 h post-KA in CA1 and DC and subsided almost completely thereafter. Loss of CA1 and, to a lesser extent, CA3 neurons became evident at 7-15 days post-KA. It was more accentuated after 1 month, accompanied by a corresponding reduction of GABA(A)-receptor staining. In contrast, DC granule cells were markedly enlarged and dispersed in the molecular layer and exhibited a prominent increase in GABA(A)-receptor subunit staining. After 4 months, the dorsal CA1 area was lost almost entirely, CA3 was reduced, and the DG represented most of the remaining dorsal hippocampal formation. No significant morphological alterations were detected contralaterally. These results suggest that loss of hilar cells and GABAergic neurons contributes to epileptogenesis in this model of MTLE. In contrast, long-term degeneration of pyramidal cells and granule cell dispersion may reflect distinct responses to recurrent seizures. Finally, GABA(A)-receptor upregulation in the DG may represent a compensatory response persisting for several months in epileptic mice.

Animals↗
PubMed2004

Minocycline prevents cholinergic loss in a mouse model of Down's syndrome.

Individuals with Down's syndrome develop Alzheimer's-like pathologies comparatively early in life, including progressive degeneration of basal forebrain cholinergic neurons (BFCNs). Cholinergic hypofunction contributes to dementia-related cognitive decline and remains a target of therapeutic intervention for Alzheimer's disease. In light of this, partial trisomy 16 (Ts65Dn) mice have been developed to provide an animal model of Down's syndrome that exhibits progressive loss of BFCNs and cognitive ability. Another feature common to both Down's syndrome and Alzheimer's disease is neuroinflammation, which may exacerbate neurodegeneration, including cholinergic loss. Minocycline is a semisynthetic tetracycline with antiinflammatory properties that has demonstrated neuroprotective properties in certain disease models. Consistent with a role for inflammatory processes in BFCN degeneration, we have shown previously that minocycline protects BFCNs and improves memory in mice with acute, immunotoxic BFCN lesions. We now report that minocycline treatment inhibits microglial activation, prevents progressive BFCN decline, and markedly improves performance of Ts65Dn mice on a working and reference memory task. Minocycline is an established antiinflammatory and neuroprotective drug and may provide a novel approach to treat specific AD-like pathologies.

Acetylcholine↗
PubMed1994

Calmodulin immunoreactivity in the chicken pineal gland: comparison with calbindin-D28k, calretinin, and S100.

Calmodulin distribution in the chicken pineal organ was investigated by immunohistochemistry. Calmodulin immunoreactivity was detected in ependymocytes in the follicular zone and in interstitial cells in the parafollicular zone. No calmodulin immunoreactivity was detected in pinealocytes. Lack of calmodulin immunoreactivity in pinealocytes raises questions about its proposed function in melatonin synthesis as suggested by pharmacological studies using calmodulin antagonists. The calmodulin distribution was comparable to that of S100, a glial cell marker. Two other markers, calbindin-D28k and calretinin, which in neuroanatomical studies give excellent cytoarchitectonic staining, in the chick pineal permitted the detection of two subclasses of pinealocytes. One was darkly stained by calbindin-D28k and rare. The other was very abundant and calretinin positive. In the parafollicular zone, calbindin-D28k and/or calretinin antibodies allowed us to visualize cells presenting a neuron-like morphology. Calretinin immunoreactivity was detected in nearly all pinealocytes in which hydroxy-indol-O-methyl transferase was also located. Comparison between the lack of calmodulin and the presence of calretinin, belonging to the same calcium-binding protein family, in chick pinealocytes raises the hypothesis about a possible role of calretinin in melatonin synthesis.

Animals↗
PubMed2003

Morphology and distribution of nitric oxide synthase-, neurokinin-1 receptor-, calretinin-, calbindin-, and neurofilament-M-immunoreactive neurons in the myenteric and submucosal plexuses of the rat small intestine.

Characterization of the enteric neurons is vital for understanding their physiological role. We have used single and dual label fluorescence and peroxidase-based immunohistochemistry in myenteric and submucosal whole mounts from the rat small intestine to evaluate the morphology and distribution of enteric neurons immunoreactive for the following phenotypic antigens: neuronal nitric oxide synthase (NOS), neurokinin-1 receptor (NK-1R), calretinin (Calr), calbindin (Cal), and neurofilament-M (NF-M). NOS-immunoreactive neurons had Dogiel type I morphology, were abundant in the myenteric plexus compared to the submucosal plexus, and never coexpressed NK-1R immunoreactivity. NK-1R- and Calr-immunoreactive neurons had Dogiel type II morphology and were distributed comparably in both plexuses. NK-1R and Calr-immunoreactivity were coexpressed in many of the same neurons. Calbindin-immunoreactive neurons exhibited four distinct morphologies: small and large Dogiel type II neurons, Dogiel type I neurons, and small elongated neurons. These neurons were significantly fewer in number in the myenteric plexus compared to the submucosal plexus. Neurofilament-M-immunoreactive neurons had three morphologies, Dogiel type II neurons, small Dogiel type II neurons, and a less common subpopulation of small, elongated, multipolar neurons. These neurons were also fewer in number in the myenteric plexus compared to the submucosal plexus. The distribution of these phenotypic markers may assist future work that elucidates the functional activities of these enteric neurons such as control of intestinal motility and adaptation to the entry of gastric contents.

Animals↗
PubMed2005

Morphomolecular neuronal phenotypes in the neocortex reflect phylogenetic relationships among certain mammalian orders.

The cytoarchitecture of the cerebral cortex in mammals has been traditionally investigated using Nissl, Golgi, or myelin stains and there are few comparative studies on the relationships between neuronal morphology and neurochemical specialization. Most available studies on neuronal subtypes identified by their molecular and morphologic characteristics have been performed in species commonly used in laboratory research such as the rat, mouse, cat, and macaque monkey, as well as in autopsic human brain specimens. A number of cellular markers, such as neurotransmitters, structural proteins, and calcium-buffering proteins, display a highly specific distribution in distinct classes of neocortical neurons in a large number of mammalian species. In this article, we present an overview of the morphologic characteristics and distribution of three calcium-binding proteins, parvalbumin, calbindin, and calretinin, and of a component of the neuronal cytoskeleton, nonphosphorylated neurofilament protein in the neocortex of various species, representative of the major subdivisions of mammals. The distribution of these neurochemical markers defined several species- and order-specific patterns that permit assessment of the degree to which neuronal morphomolecular specialization, as well as the regional and laminar distribution of distinct cell types in the neocortex, represents derived or ancestral features. In spite of the remarkable diversity in morphologic and cellular organization that occurred during mammalian neocortical evolution, such patterns identified several associations among taxa that closely match their phylogenetic relationships.

Animals↗
PubMed2002

Neurochemical organization of the human basal ganglia: anatomofunctional territories defined by the distributions of calcium-binding proteins and SMI-32.

The distribution of the calcium-binding proteins calbindin-D28K (CB), parvalbumin (PV) and calretinin (CR), and of the nonphosphorylated neurofilament protein (with SMI-32) was investigated in the human basal ganglia to identify anatomofunctional territories. In the striatum, gradients of neuropil immunostaining define four major territories: The first (T1) includes all but the rostroventral half of the putamen and is characterized by enhanced matriceal PV and SMI-32 immunoreactivity (-ir). The second territory (T2) encompasses most part of the caudate nucleus (Cd) and rostral putamen (PuT), which show enhanced matriceal CB-ir. The third and fourth territories (T3 and T4) comprise rostroventral parts of Cd and PuT characterized by complementary patch/matrix distributions of CB- and CR-ir, and the accumbens nucleus (Acb), respectively. The latter is separated into lateral (prominently enhanced in CB-ir) and medial (prominently enhanced in CR-ir) subdivisions. In the pallidum, parallel gradients also delimit four territories, T1 in the caudal half of external (GPe) and internal (GPi) divisions, characterized by enhanced PV- and SMI-32-ir; T2 in their rostral half, characterized by enhanced CB-ir; and T3 and T4 in their rostroventral pole and in the subpallidal area, respectively, both expressing CB- and CR-ir but with different intensities. The subthalamic nucleus (STh) shows contrasting patterns of dense PV-ir (sparing only the most medial part) and low CB-ir. Expression of CR-ir is relatively low, except in the medial, low PV-ir, part of the nucleus, whereas SMI-32-ir is moderate across the whole nucleus. The substantia nigra is characterized by complementary patterns of high neuropil CB- and SMI-32-ir in pars reticulata (SNr) and high CR-ir in pars compacta (SNc) and in the ventral tegmental area (VTA). The compartmentalization of calcium-binding proteins and SMI-32 in the human basal ganglia, in particular in the striatum and pallidum, delimits anatomofunctional territories that are of significance for functional imaging studies and target selection in stereotactic neurosurgery.

Aged↗
PubMed2002

Patterns of expression of calcium binding proteins and neuronal nitric oxide synthase in different populations of hippocampal GABAergic neurons in mice.

We examined the expression of calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin D28K (CB), and neuronal nitric oxide synthase (nNOS) in gamma-aminobutyric acid (GABA)ergic neurons of the mouse hippocampus, with particular reference to areal and dorsoventral differences. First, we estimated the colocalization of the calcium binding proteins and nNOS. GABAergic neurons containing both PV and nNOS, i.e., PV-immunoreactive (-IR)/nNOS-IR neurons, were rare in Ammon's horn but frequent in the dentate gyrus (DG). CR-IR/nNOS-IR neurons and CB-IR/nNOS-IR neurons were frequent in Ammon's horn but rare in the DG. In the entire hippocampus, the percentage of CR-IR neurons containing nNOS was significantly higher at the ventral level (44.3%) than at the dorsal level (17.0%). The percentage of CB-IR neurons containing nNOS was also significantly higher at the ventral level (42.3%) than at the dorsal level (29.3%). Next, we estimated the numerical densities (NDs) of calcium binding protein-containing GABAergic neurons. The ND of PV-IR neurons was comparable at the dorsal (1.16 x 10(3)/mm(3)) and ventral levels (1.23 x 10(3)/mm(3)), respectively. The ND of CR-IR neurons was less at the dorsal level (0.52 x 10(3)/mm(3)) than at the ventral level (0.64 x 10(3)/mm(3)). The ND of CB-IR neurons was also less at the dorsal level (0.91 x 10(3)/mm(3)) than at the ventral level (1.57 x 10(3)/mm(3)). Overall, approximately half of the GABAergic neurons contained one of the three calcium binding proteins (45% at the dorsal level and 47% at the ventral level). These data establish a baseline for examining potential roles of GABAergic neurons in hippocampal network activity in mice.

Animals↗