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PubMed1990

Distribution of parvalbumin immunoreactivity in the rat septal area.

The distribution of parvalbumin (PV)-containing neurons and processes in the septal area of the rat brain was studied using a monoclonal antibody and the avidin-biotin immunoperoxidase method. PV-immunoreactive neurons were mainly located in the medial septum/diagonal band complex and in the horizontal limb of the diagonal band of Broca, showing a high density of heavily immunostained neurons and fibers. Nonimmunoreactive cells surrounded by PV-positive cells and processes were observed in the same region, but no pericellular basket-like arrangements were found. On the contrary, the dorsal, intermediate, and ventral nuclei of the lateral septum were practically devoid of PV-positive neurons and processes. Thus, in these nuclei only a very low density of isolated neurons was labeled; these were specially scattered in the ventrolateral septal nucleus and in the dorsolateral septal nucleus just below the corpus callosum. Delicate PV-positive axonal plexuses were also observed in the dorsal and intermediate nuclei of the lateral septum. The immunopositive neurons displayed very different sizes and morphologies among the various septal nuclei and inside each of them, indicating that they do not belong to a single morphological class of neurons. Finally, the distribution of PV in the rat septal area is not directly related to cholinergic and GABAergic septal neurons.

Animals↗
PubMed1992

Distribution of calbindin D-28K and parvalbumin immunoreactivities in the nucleus olfactorius anterior of the rat.

The distributions of calbindin D-28K (CaBP) and parvalbumin (PV) in the rat nucleus olfactorius anterior (NOA) were described using monoclonal antibodies and the avidin-biotin-peroxidase method. The NOA showed a high immunoreactivity for CaBP, with a rostrocaudal increase in the positive neurons and fibres. Pars externa (NOAe) was the only subdivision which showed a low CaBP immunostaining. PV-positive elements were less abundant than those CaBP immunostained. The main difference in the distributions for both proteins was observed in the pars medialis which was practically PV negative. PV- and CaBP-stained neurons showed similar morphologies in the subdivisions where they were present. In NOAe, we observed a characteristic PV- and CaBP-positive neuronal type, with an oriented dendritic pattern. Transition areas were clearly observable in both CaBP- and PV-labelled sections.

Animals↗
PubMed1993

Absence of calcium-induced LTP-like response in the dentate area of seizure-prone gerbils and its relation to parvalbumin in the entorhinal perforant path synapse of this species.

Mongolian gerbils (Meriones unguiculatus) are genetically predisposed to seizures, for which an involvement of hippocampal hyperexcitability and disinhibition has been suggested. The response in vitro of the hippocampal synaptic circuit upon exposure to an elevated extracellular calcium concentration is well known in the rat, and its dependence on inhibitory and excitatory transmission has been thoroughly studied. The purpose of the present investigation was to compare the influence of elevated extracellular calcium on inhibitory and excitatory transmission in the dentate area and the CA1 field of gerbil and rat hippocampal slices. Elevated calcium induced in the CA1 area of both animal species a long-term potentiation (LTP)-like response. Upon calcium exposure in the dentate area a decrease in population spike amplitude occurred in both gerbil and rat slices, indicating a similar degree of synaptic inhibition in the two species. However, in contrast to the effects known in the rat, elevated extracellular calcium failed to enhance the excitatory postsynaptic potential in the gerbil dentate area. This difference may depend on the species-specific, selective presence of the calcium-binding protein parvalbumin in perforant path terminals of the gerbil, which may be relevant to the susceptibility to seizures of this animal species.

Animals↗
PubMed1993

Expression of gamma-aminobutyric acid and calcium binding protein-parvalbumin by chick motoneurons.

The expression of calcium binding protein parvalbumin (PV) and gamma-aminobutyric acid (GABA) was studied in the chick motoneurons by using pre- and postembedding immunocytochemistry. Our data reveal that PV and GABA are colocalized in the majority, but not all, of chick lumbo-sacral spinal motoneurons innervating the somatic muscles. It is suggested that, in this neuromuscular system, GABA does not act as a classical inhibitory neurotransmitter but, combined with calcium, could be involved, at least in part, in the maintenance of neurons and the prevention of cell death as in certain neurodegenerative disorders.

Animals↗
PubMed1995

Nimodipine prevents early loss of hippocampal CA1 parvalbumin immunoreactivity after focal cerebral ischemia in the rat.

The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the lateral part of the CA1 region, while PV-ir was not altered in the CA2 and CA3 areas. Pretreatment with the L-type Ca2+ channel blocker nimodipine prevented the ischemia-induced loss of PV-ir in the CA1, suggesting a role for L-type voltage sensitive calcium channels in the mechanism of early neuronal alterations in the hippocampus CA1 region after focal cerebral ischemia.

Animals↗
PubMed1996

The proteoglycan DSD-1-PG occurs in perineuronal nets around parvalbumin-immunoreactive interneurons of the rat cerebral cortex.

Proteoglycans involved in the shaping of the developing brain are often preserved in the adult brain in more restricted locations. We have studied the fate of DSD-1-PG, a chondroitin sulfate proteoglycan containing the hybrid epitope DSD-1. DSD-1-PG exerts neurite outgrowth promoting activity and has been shown to occur in the developing brain during late brain development and into adulthood. In the adult rat brain, monoclonal and polyclonal antibodies against DSD-1-PG labelled only the circumference of a selected subpopulation of neurons. These nerve cells invariably expressed the calcium-binding protein parvalbumin. The label occupied the extracellular space in close vicinity to the cell body, surrounding axon terminals and glial end feet, but was absent from synaptic clefts. DSD-1-PG is thus shown to be an additional representative of the growing list of substances found in perineuronal locations in the adult mammalian brain.

Animals↗
PubMed1995

Distribution of parvalbumin-containing interneurons in the hippocampus of the gerbil--a qualitative and quantitative statistical analysis.

In the gerbil (Meriones unguiculatus) hippocampal formation, the calcium-binding protein parvalbumin (PV) shows a unique species-specific distribution: it is present in the perforant path from the entorhinal cortex to the stratum molecular of the dentate are and cornu ammonis. A possible relation of this to the seizure-sensitivity of gerbils has been suggested. In addition, as in other species, PV is contained in a subpopulation of GABAergic nerve cells of the gerbil hippocampus. The characteristics of these PV-containing neurons are here described. Distribution and shape of the PV-positive neurons in general agreed with the features described for rat hippocampus with two notable exceptions: in CA2 PV-containing perikarya were densely crowded and gave rise to an intense immunoreactive plexus around the pyramidal cells and, in CA1, the number of stained neurons was variable, often much lower than in rats and occasionally not a single PV-positive neuron was present. In parasagittal brain sections of the lateralities 1.0, 1.6 and 2.2 mm from the midline, obtained from 27 male gerbils, the number of PV-containing neurons was determined. The data set obtained in CA3 and dentate area resembled unimodal distributions, while in CA1 a bimodal frequency distribution was present. Since parametric and non-parametric correlation tests rely on a unimodal distribution of the data set, they gave falsely significant values in CA1. The bimodal distribution suggests that, with respect to the PV-containing interneurons in CA1, two different populations of gerbils were included in our sample, those with many positive neurons and those with only a few. Since the nerve terminal staining is preserved also in those gerbils with only a few positive perikarya in CA1, it seems possible that an unknown factor influenced PV expression and storage in the soma. Sex, age, seasonal or circadian rhythm or quality of immunocytochemical staining did not influence the outcome of the quantitative analysis. However, a relation of the expression of the high affinity calcium buffering PV in interneurons and the individual seizure sensitivity of the gerbil is considered.

Age Factors↗
PubMed1996

A light and electron microscopic study of NADPH-diaphorase-, calretinin- and parvalbumin-containing neurons in the rat nucleus accumbens.

The rat nucleus accumbens contains medium-sized, spiny projection neurons and intrinsic, local circuit neurons, or interneurons. Sub-classes of interneurons, revealed by calretinin (CR) or parvalbumin (PV) immunoreactivity or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, were compared in the nucleus accumbens core, shell and rostral pole. CR, PV and NADPH-diaphorase-containing neurons are shown to form three non-co-localising populations in these three areas. No significant differences in neuronal population densities were found between the subterritories. NADPH-diaphorase-containing neurons could be further separated morphologically into three sub-groups, but CR- and PV-immunoreactive neurons form homogeneous populations. Ultrastructurally, NADPH-diaphorase-, CR- and PV-containing neurons in the nucleus accumbens all possess nuclear indentations. These are deeper and fewer in neurons immunoreactive for PV than in CR- and NADPH-diaphorase-containing neurons. CR-immunoreactive boutons form asymmetrical and symmetrical synaptic specialisations on spines, dendrites and somata, while PV-immunoreactive boutons make only symmetrical synaptic specialisations. Both CR- and PV-immunoreactive boutons form symmetrical synaptic specialisations with medium-sized spiny neurons and contact other CR- and PV-immunoreactive somata, respectively. A novel non-carcinogenic substrate for the peroxidase reaction (Vector Slate Grey, SG) was found to be characteristically electron-dense and may be distinguishable from the diaminobenzidine reaction product. We conclude that the three markers used in this study are localised in distinct populations of nucleus accumbens interneurons. Our studies of their synaptic connections contribute to an increased understanding of the intrinsic circuitry of this area.

Analysis of Variance↗
PubMed1995

Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons.

Homozygous Igf1-/- mice at 2 months of age had reduced brain weights, with reductions evenly affecting all major brain areas. The gross morphology of the CNS was normal, but the size of white matter structures in brain and spinal cord was strongly reduced, owing to decreased numbers of axons and oligodendrocytes. Myelinated axons were more strongly reduced in number than unmyelinated axons. The volume of the dentate gyrus granule cell layer was reduced in excess of the decrease in brain weight. Among populations of calcium-binding protein-containing neurons, there was a selective reduction in the number of striatal parvalbumin-containing cells. Numbers of mesencephalic dopaminergic neurons, striatal and basal forebrain cholinergic neurons, and spinal cord motoneurons were unaffected. Cerebellar morphology was unaltered. Our findings suggest cell type- and region-specific functions for IGF-I and emphasize prominent roles in axon growth and maturation in CNS myelination.

Animals↗
PubMed2004

Parvalbumin-like immunostaining in the cat inferior colliculus. Light and electron microscopic investigation.

The presence of the calcium-binding protein parvalbumin (PV) was studied in neuronal elements of the cat's inferior colliculus (IC) by means of light and electron microscopic immunocytochemistry. Immunostaining of PV was detected in all three main parts of the IC. Several subtypes of large neurons that differed in size and shape were immunostained, comprising approx. 15% of the total number of PV-containing neurons. Approx. half of the labeled neurons were medium sized. Two types of small neurons were found to be PV synthesizing, and comprised approx. 35% of the total PV-containing population. Ultrastructurally, many dendrites were heavily immunolabeled, and the reaction product was present in dendritic spines as well. Several types of synaptic boutons contained reaction product, and terminated on both labeled and unlabeled postsynaptic targets forming asymmetric and symmetric synapses. Approx. 70% of all PV-immunolabeled terminals contained round synaptic vesicles and formed asymmetric synapses. The majority of these boutons were of the "large round" type and corresponded to the terminals of cochlear nuclei. A lower number were of the "small round" type, and were probably corticotectal terminals. The remaining 30% of PV-containing terminals contained pleomorphic or elongated vesicles and formed symmetric synapses. These terminals corresponded with "P" and "F1" bouton types. Part of these boutons appeared to arise from nuclei of the lateral lemniscus and the superior olive, and a certain percentage likely represented endings of inhibitory interneurons.

Animals↗
PubMed2006

Up-regulation of parvalbumin expression in newborn and adult rat heart.

Parvalbumin (PV), a cytoplasmic calcium-binding protein, functions as a relaxing factor and has recently been detected in rat heart. Developmental changes in PV localization and expression were investigated in the heart of Wistar rats at different ages. Ten hearts from newborn, 3-month-old (young), 6-month-old (young adult), and 12-month-old (adult) rats were processed for immunohistochemistry and Western blot assay. PV was detected in hearts of all the age groups of the rats from newborn to 12-month-old by both immunohistochemistry and Western blotting. A variable distribution of PV immunoreactivity was present in newborn cardiac myocytes. In the 3-, 6-, and 12-month-old rat hearts, identical PV immunoreactivity was found in all cardiac myocytes and the intensity of PV immunoreactivity increased with increasing age. By using Western blotting, it was found that the expression of PV was low in the newborn rat heart and increased with increasing age. The presence of PV may correlate with the physiological age, and possibly serves to maintain proper relaxation of the cardiac myocytes to cope with an increasing workload of the heart during body growth.

Aging↗
PubMed2006

Parvalbumin in the cat claustrum: ultrastructure, distribution and functional implications.

The presence of the calcium-binding protein (CaBP) parvalbumin (PV) in the neuronal elements of the cat's dorsal claustrum was studied by immunohistochemistry at the light- and electron-microscopic level. PV-immunoreactive neurons and fibers were detected in all parts of the claustrum. The PV-immunoreactive neurons were divided into several subtypes according to their size and shape. Approximately 7% of all PV-immunoreactive neurons were classified as large, while approximately half of the labeled neurons were medium-sized. The small PV-immunoreactive neurons were 45% of the total PV-immunoreactive neuronal population. Ultrastructurally, many spiny and aspiny dendrites were heavily immunolabeled, and the reaction product was present in dendritic spines as well. Several types of synaptic boutons containing reaction product were also found. These boutons terminated on both labeled and unlabeled postsynaptic targets (soma, dendrites, etc.), forming asymmetric or symmetric synapses. Approximately 70% of all PV-immunoreactive terminals contained round synaptic vesicles and formed asymmetric synapses. The majority of these boutons were of the ''large round'' type. A lesser percentage were of the ''small round'' type. This paper represents the first study demonstrating the existence of PV, a CaBP, in the cat claustrum, and its distribution at the light and electron microscope level. Beyond the relevance of this research from the standpoint of adding to the paucity of literature on PV immunoreactivity in the claustrum of various other mammals (e.g. monkey, rabbit, rat, mouse), it is of particular significance that the cat claustrum is more similar to the rabbit claustrum than to any other mammalian species studied thus far, noted by the existence of four distinct morphologic subtypes. We also demonstrate a lack of intrinsic, and possibly functional, heterogeneity as evidenced by the uniform distribution of PV throughout the cat claustrum, across the four cell subtypes (i.e. inhibitory interneurons as well as projection neurons). Indeed, the association with, and influence of, the cat claustrum on diverse multisensory mechanisms may have more to do with its afferent than efferent relationships, which speaks strongly for its importance in the sensory hierarchy. Exactly what role PV plays in the claustrum is subject to discussion, but it can be postulated that, since CaBP is associated with GABAergic interneurons, synaptogenesis and neuronal maturation, it may also serve as a neuroprotectant, particularly with regard to pathologies associated with the aging process, such as in Alzheimer's disease.

Animals↗
PubMed2006

Differential effects of embryo transfer and maternal factors on anxiety-related behavior and numbers of neuropeptide Y (NPY) and parvalbumin (PARV) containing neurons in the amygdala of inbred C3H/HeN and DBA/2J mice.

The effects of reciprocal embryo transfers were studied on anxiety-related behavior of inbred C3H/HeN and DBA/2J mice on the elevated plus maze (EPM), and related to amygdaloid neuropeptide Y (NPY)- and parvalbumin (PARV)-immunoreactive neurons. Embryo transfer significantly reduced closed arm entries in in-stain-transferred C3H mice, and maternal factors influenced open arm entries only in interaction with genetic background and sex. In DBA/2J-mice, embryo transfer resulted in a reduced number of NPY-immunoreactive (NPY-ir) neurons, while PARV-immunoreactive (PARV-ir) cells were not affected. In C3H/HeN mice, however, in-strain embryo transfer only resulted in a reduction of the number of PARV-immunoreactive neurons. Maternal factors mainly induced changes in the number of NPY-ir neurons in the basolateral complex of the amygdala either directly or in interaction with genetic factors. In summary, in-strain embryo transfer had a minor effect on the behavior of C3H/HeN mice, and a differential influence on the numbers of amygdaloid NPY-ir and PARV-ir neurons of inbred C3H/HeN and DBA/2J mice. Maternal factors had a stronger impact on the numbers of NPY-ir neurons than PARV-ir neurons. The present results indicate that alterations in behavior and amygdala morphology induced by embryo transfer or maternal factors depend on the genetic background of the mouse strains used.

Amygdala↗
PubMed2006

Parvalbumin neurons in the entorhinal cortex of subjects diagnosed with bipolar disorder or schizophrenia.

BACKGROUND: Growing evidence indicates that the entorhinal cortex (ECx) might be affected in schizophrenia (SZ) and bipolar disorder (BD). To test whether distinct interneuronal subpopulations might be altered, numbers of parvalbumin-immunoreactive (PVB-IR) neurons were measured in the ECx of BD and SZ subjects. These neurons play a pivotal role within ECx intrinsic circuits. METHODS: Numbers, numerical density, and soma size of PVB-IR neurons were measured in the ECx of normal control (n = 16), BD (n = 10), and SZ (n = 10) subjects. The volume of the ECx was measured in Nissl-stained sections. RESULTS: In BD, decreases of total numbers (p = .02) and numerical densities (p = .01) of PVB-IR neurons were detected in the ECx. Within distinct subregions, reductions were detected in the superficial layers of the lateral (p = .02), intermediate (p = .04), and caudal (p = .01) ECx. In SZ, total numbers and numerical densities were not altered. A reduction of soma size was present in the intermediate ECx (p = .01). Volume was unaffected in either disorder. CONCLUSIONS: In BD, a decrease of PVB-IR neurons may alter intrinsic inhibitory networks within the superficial layers of the ECx. The likely consequence is a disruption of integration and transfer of information from the cerebral cortex to the hippocampus.

Adult↗
PubMed2004

Spatial analysis reveals alterations of parvalbumin- and calbindin-positive local circuit neurons in the cerebral cortex of mutant mdx mice.

The aim of the present study was to investigate the spatial organization of selected populations of local circuit neurons in the cerebral cortex of the mutant mdx mouse, an acknowledged model of Duchenne Muscular Dystrophy. To this purpose, we quantified and compared the distribution of parvalbumin- and calbindin-positive neurons in the motor, somatosensory, visual, and anterior cingulate cortices of wild-type and mdx mice. The methodological approach was based on generation of two-dimensional Voronoi polygons from digital charts of the cell populations visualized immunohistochemically. Polygon areas were then analyzed and the derived coefficients of variation were statistically compared. Using this strategy, we were able to reveal, in mdx mice, changes involving both the above populations of interneurons. These changes were evident in the motor and anterior cingulate cortices but not in the somatosensory and visual cortices. In addition, the changes of coefficients of variation were area-specific in the cortex of mdx mice. The values increased in the motor cortex and decreased in the anterior cingulate cortex with respect to the corresponding values of wild-type animals. The present findings point out widespread alterations in the mdx cortex involving also areas not primarily related to sensorimotor integration. In addition, we demonstrate that cortical alterations of the local circuit machinery are characterized in mdx mice by individual regional differences.

Animals↗
PubMed2005

Dopamine manipulation alters immediate-early gene response of striatal parvalbumin interneurons to cortical stimulation.

Cortical projections provide the major excitatory inputs to the striatum. In addition to innervating medium spiny cells, these axons contact striatal interneurons that are parvalbumin-immunoreactive (PV-ir). PV-ir interneurons make synaptic connections with many medium spiny cells, and thus can modulate striatal output. The striatum also receives dopaminergic projections from the substantia nigra, but it has been challenging to study the impact of dopamine (DA) cell injury on corticostriatal activity in vivo due to limitations in the methods used to induce cortical activity. Using epidural application of the GABA(A) antagonist picrotoxin, which produces a topographically restricted region of striatal immediate-early gene expression, we have investigated the effect of DA cell injury or DA receptor antagonism on immediate-early gene (IEG) expression in striatal medium spiny cells and PV-ir interneurons. Epidural application of picrotoxin to the rat's M1 motor cortex induced Fos in ipsilateral dorsolateral striatum. Animals previously given 6-hydroxydopamine (6-OHDA) injections into the ascending DA pathways had greater total numbers of cortical stimulation-induced striatal Fos-ir cells but fewer Fos-ir/PV-ir cells, compared to sham-operates. In a separate experiment, rats given cortical stimulation and treated with the DA D2-class antagonist eticlopride (0.10 mg/kg) exhibited fewer Fos-ir/PV-ir cells than did vehicle-treated rats. Taken together, these results indicate that DA may importantly control striatal output via influences on PV-ir interneurons. Possible mechanisms for these influences are discussed.

Adrenergic Agents↗
PubMed2005

Evidence for a perisomatic innervation of parvalbumin-containing interneurons by individual pyramidal cells in the basolateral amygdala.

The basolateral amygdala (ABL) contains pyramidal projection neurons (PNs) and several discrete subpopulations of nonpyramidal interneurons. Interneurons containing the calcium-binding protein parvalbumin (PV) constitute about half of all ABL interneurons, and provide a robust innervation of the perisomatic domain of PNs. Although it is known that PNs reciprocate this projection by innervating PV interneurons, little is known about the details of these connections. In the present study, we investigated the innervation of PV interneurons by individual PNs in rat amygdalar slices. PNs in the basolateral nucleus, identified in vitro by their distinctive electrophysiological characteristics in whole cell patch-clamp recordings, were filled with biocytin by diffusion from the patch electrode. PV interneurons and biocytin-labeled PNs were visualized with a two-color immunoperoxidase procedure using nickel-enhanced DAB (black) for biocytin and non-enhanced DAB (brown) for PV. In slices with well-stained PN axons and PV neurons, light microscopy revealed numerous synapse-like contacts between these structures. The main PV+ targets of PN axons were the somata and proximal dendrites of PV neurons, although there were also contacts with more distal PV dendrites. In many cases, the PN axons ran along PV somata and/or proximal dendrites, forming multiple contacts. However, the great majority the PN axon terminals did not contact PV neurons. These observations suggest that there are robust reciprocal perisomatic PN-to-PV connections that may be important for the precise timing of rhythmic activity in the basolateral amygdala.

Amygdala↗
PubMed2006

Distribution of calbindin-28kD and parvalbumin in V1 in normal adult Cebus apella monkeys and in monkeys with retinal lesions.

Several proteins have their normal patterns of distributions altered by monocular visual deprivation. We studied the distribution of the calcium-binding proteins calbindin-28kD (Cb) and parvalbumin (Pv) in V1 in normal adult Cebus apella monkeys and in monkeys with monocular retinal lesions. In normal monkeys, the interblobs regions in layers 2/3 and the layer 4B are intensely labeled for Cb, while Pv reaction showed a complementary labeling pattern with a stronger staining in layers 4A, 4C and in the blob regions in layers 2/3. In monkeys with monocular retinal lesion, the laminar distribution of these proteins was differentially affected, although both reactions resulted in stronger labeling in non-deprived ocular dominance columns. While Cb reaction resulted in stronger labeling in layers 1 through 5, Pv labeling was heavier in layers 2/3, 4A and 4C. There was a clear reduction in the intensity of neuropil staining for both Pv and Cb in deprived ocular dominance columns with little or no reduction in number of labeled cells. This reduction could thus be attributed to activity-dependent changes at synapses level.

Animals↗