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PubMed1995

Developmental expression of parvalbumin mRNA in the cerebral cortex and hippocampus of the rat.

Parvalbumin (PARV) belongs to the family of calcium-binding proteins bearing the EF hand domain. Immunocytochemical studies in the cerebral cortex have demonstrated that neurons containing PARV include two types of GABAergic interneurons, namely, basket and axo-axonic chandelier cells. The present study examines the onset and pattern of PARV mRNA expression during the development of rat neocortex and hippocampus by means of 'in situ' hybridization with an oligonucleotide probe corresponding to rat PARV cDNA. In animals aged P0-P6 no signal was detected above background in neocortex or hippocampus. At P8, a few cortical cells displayed a number of silver grains just above background levels. By P10 PARV mRNA-expressing cells in the neocortex were detected almost exclusively in layer V of somatosensory, frontal and cingulate cortices. At P12 PARV mRNA was mainly detected in layers IV, V and VIa. By P14 there was a marked overall increase in the entire neocortex, including layer II-III, both in the number of cells and in their intensity of labelling. Further maturation in the pattern of PARV mRNA concentration was observed between P16 and P21. In the hippocampus low hybridization was observed at P10-P12. In subsequent stages both the number of positive cells and the intensity of labelling increased steadily. No clear-cut radial gradients for the expression of PARV mRNA were observed in the hippocampal region. Our results show that the developmental radial gradient followed by PARV mRNA expression in the neocortex does not follow an 'inside-out' gradient, consistent with previous immunocytochemical findings. Taken together, these data indicate that the developmental sequence followed by the PARV protein directly reflects mRNA abundance and suggest that PARV mRNA expression correlates with the functional maturation of cortical interneurons.

Animals↗
PubMed1992

Postnatal development of parvalbumin immunoreactivity in axon terminals of basket and chandelier neurons in monkey neocortex.

1. Two classes of GABAergic inhibitory interneurons, chandelier and basket cells, are known regulators of pyramidal neurons. Parvalbumin (PV) a calcium binding protein, has been shown to be a marker for axon terminals of subpopulations of these interneurons. 2. Immunohistochemical methods were used in this study to examine changes in the distribution of PV-immunoreactive (IR) chandelier and basket axon terminals during postnatal development of monkey neocortex. 3. Our results indicate a differential effect of postnatal development on PV-IR axon terminals of chandelier and basket neurons that is region-specific. 4. The differential regional, laminar and developmental pattern of PV-IR axon terminals of chandelier and basket cells may provide insight into the functional role of these classes of inhibitory neurons in primate neocortex.

Aging↗
PubMed1978

Thermodynamic investigations of proteins. IV. Calcium binding protein parvalbumin.

The conformational transitions of calcium binding protein parvalbumin III from carp muscle were studied by scanning calorimetry, potentiometric titration and isothermal calorimetric titration. Changes of Gibbs energy, enthalpy and partial heat capacity were determined. The removal of calcium ions by EDTA is accompanied by 1) a heat absorption of 75 +/- 10 kJ per mole of the protein, 2) a decrease in the Gibbs energy of protein structure stabilisation of about 42 kJ mol-1 and 3) a decrease in thermostability by more than 50 K. The protonation of the acidic groups leads to a loss of calcium followed by denaturation, while the pH of the transition strongly depends on calcium activity. The enthalpy and heat capacity changes at denaturation are comparable with the values observed for other compact globular proteins.

Animals↗
PubMed1982

Intrinsic fluorescence spectra of a tryptophan-containing parvalbumin as a function of thermal, pH and urea denaturation.

The thermal, pH and urea denaturation of the calcium-loaded protein from whiting has been studied by means of the intrinsic fluorescence of the single tryptophan residue. pH denaturation of the protein takes place at a pH greater than 11.5 and lower than 5.5. Thermal denaturation of the protein occurs at temperatures above 55 degrees C. Urea initiates the denaturation of the calcium-loaded protein at rather low concentrations (1.0 M). In all cases, whether pH, thermal or urea denaturation, intermediate states of the protein were recorded. The fluorescence spectra of these intermediates are similar to that of the protein with one equivalent of calcium bound. Whiting parvalbumin binds calcium in the presence of 7.5 M urea but under these conditions, calcium-binding constants of the protein have been shown to be 10(2)-10(3)M(-1) (in comparison with 5 X 10 (8) and 6 X 10(6)M(-1) in the absence of any denaturing agents).

Animals↗
PubMed1985

Parvalbumin in rat cerebrum, cerebellum and retina during postnatal development.

Radioimmunoassay and immunohistochemical studies were performed on the occurrence and distribution of parvalbumin-like immunoreactivity (PA-LI) in developing rat cerebrum, cerebellum and retina. No PA-LI was detected in the nervous tissues of the newborn animals. In the cerebrum, the PA-LI appeared in non-pyramidal neurons at the 2nd postnatal week and increased linearly until the 8th week. In the cerebellum, a rapid increase in the PA-LI took place at the 2nd week, with an enrichment of the antigen to Purkinje neurons. In the retina, amacrine cells contained PA-LI, the levels of which increased from the 2nd to 4th week. Regulation of intracellular Ca2+ concentration may be one of the important factors for the maturation of the central nervous system.

Animals↗
PubMed1990

Short-term changes of parvalbumin and calbindin immunoreactivity in the rat hippocampus following cerebral ischemia.

The calcium-binding proteins, parvalbumin (PV) and calbindin (CaBP), were used as immunocytochemical markers for two different interneuron populations in the rat hippocampus shortly after transient cerebral ischemia. Besides in interneurons, CaBP immunoreactivity (-i) is located in hippocampal CA1 pyramidal cells and dentate granule cells. Shortly after ischemia, the PV-i and CaBP-i were unchanged but, around the 4th postischemic day, PV-i disappeared from somata and fibers located in CA1, CA3c, and the dentate hilus. Terminal PV-i was unchanged. Within days, the PV-i gradually reappeared, first in somata and then in fibers. The transient loss of PV-i was, on a time scale, closely accompanied by a permanent loss of CaBP-i in CA1 pyramidal cells. CaBP-i in interneurons was unchanged. In order to examine the effect of an increased intracellular calcium concentration on the PV-i and CaBP-i, the calcium ionophore A23187 was stereotaxically injected into CA1. In rats killed 30 min later and processed for PV-i and CaBP-i, both PV-i and CaBP-i had disappeared around the A23187 injection sites. Based on this observation and the changes observed after ischemia, it is suggested that the hippocampal PV-i interneurons suffer from a delayed and reversible calcium accumulation in the days after ischemia. Concomitantly, there could be a decreased synthesis or increased destruction of PV after ischemia.

Animals↗
PubMed1990

Parvalbumin in rat superior colliculus.

Parvalbumin-like immunoreactivity (PA-LI) has been studied in sections of the superior colliculus (SC) of the rat and its distribution compared to the patterns of acetylcholinesterase (AChE) and cytochrome oxidase (CO) staining. In the intermediate layers it was found that PA-LI is spatially associated with AChE only in the medial part of the SC, but assumes a complementary distribution further laterally. There was a positive correlation between PA-LI and CO. We conclude that the patterns of PA-LI and CO are not systematically related to collicular input known to be associated with the AChE-rich zones, but may reflect adherence to channel separation beyond the terminal fields of clustered afferents.

Acetylcholinesterase↗
PubMed1990

Cerebral cortical calbindin D28K and parvalbumin neurones in Down's syndrome.

Anti-calbindin D28K (CaBP) and anti-parvalbumin (PVA) antibodies were used to study the number and size of neurones containing these two calcium binding proteins in post-mortem brains from 7 neurologically normal controls and from 4 elderly patients with clinically diagnosed Down's syndrome (DS) and whose brains contained numerous senile plaques and neurofibrillary tangles. The possible co-existence of these two calcium binding proteins in human cerebral cortex was also examined. In the controls, CaBP immunoreactive neurones were mainly non-pyramidal neurones although some pyramidal neurones were also CaBP immunoreactive. All the PVA immunoreactive neurones were non-pyramidal cells. CaBP and PVA did not apparently co-exist with each other in cortical neurones. When compared with the neurologically normal controls, the number and size of CaBP and PVA immunoreactive neurones were significantly reduced in the cortex of patients with DS. These findings show that CaBP and PVA containing cortical neurones are affected in elderly persons with DS.

Aged↗
PubMed1990

Late appearance of parvalbumin-immunoreactivity in the development of GABAergic neurons in the rat hippocampus.

The calcium-binding protein parvalbumin (PARV) is supposed to have a protective function under conditions of experimental seizure and hypoxia in a subgroup of GABAergic inhibitory neurons in the adult rat hippocampus. Here we studied the appearance of PARV immunoreactivity in rat hippocampal non-pyramidal cells during postnatal development in comparison to glutamate decarboxylase (GAD) immunoreactivity. PARV-immunoreactive neurons were not observed before postnatal day 7 whereas GAD-positive neurons and terminal-like puncta were present at postnatal day 2 (P2) and were frequent around P5. From other studies it is known that all GABAergic neurons are formed prenatally. Our data thus indicate that in the early postnatal period GABAergic non-pyramidal cells are poorly protected by calcium-binding proteins against a pathological calcium influx.

Animals↗
PubMed1992

Reorganization of input synapses of parvalbumin-containing neurons in the rat fascia dentata following entorhinal lesion.

Removal of ipsilateral entorhinal afferents to the fascia dentata results in a retraction of postsynaptic parvalbumin (PARV)-containing dendrites of GABAergic neurons from the outer molecular layer. This study analyzes the reorganization of input synapses of these identified neurons following deafferentation. The density of synaptic input (total length of synaptic membrane specializations) of PARV-immunostained dendrites increased by 34% in the outer molecular layer of the fascia dentata 8 days, and by 21% 55 days following lesion when compared with unoperated controls. Eight days postlesion this increase was mainly due to an enlargement of synaptic membrane specializations of single terminals whereas 55 days after the lesion there was an increase in the number of synapses on the identified dendrites. Our results suggest expansion of terminals of remaining afferent systems (i.e. commissural fibers) in the early postlesional period and reactive synaptogenesis (i.e. de novo formation of synaptic contacts) on PARV-positive dendrites after long survival time. This increased innervation may be of functional importance as it might compensate for the reduction of the receptive field of the PARV-positive, supposedly inhibitory neurons in the postlesional dentate gyrus.

Animals↗
PubMed1992

Late appearance of parvalbumin-immunoreactive neurons in the rodent cerebral cortex does not follow an 'inside-out' sequence.

Parvalbumin (PARV), a Ca(2+)-binding protein believed to play a role in neuronal excitability, is contained in certain GABAergic inhibitory neurons of the cerebral cortex. Here we report that expression of PARV in the developing neocortex of rats and mice occurs with a sequence which does not follow the usual 'inside-out' gradient of cortical development. Thus, PARV-immunoreactive neurons appear first in layer V and only thereafter in the remaining cortical layers. An adult-like pattern of immunoreactivity is reached simultaneously in layers II-III and VIb. These observations indicate that the mechanisms regulating the functional maturation of PARV-containing inhibitory neurons are different from those that generally govern developmental processes in the cortex.

Animals↗
PubMed1993

'Perineuronal nets' around cortical interneurons expressing parvalbumin are rich in tenascin.

'Perineuronal nets' are ill-known structures enwrapping the cell bodies and proximal dendrites of certain neurons in the brain. It is as yet unclear if they represent a cytological entity or extracellular material. Using immunohistochemical methods we have detected the presence of the extracellular matrix-protein, tenascin, in the 'perineuronal nets' surrounding certain cortical interneurons. We have also shown that tenascin antibodies label the circumference of parvalbumin-immunoreactive neurons preferentially. We conclude that this classical matrix protein is a major component of 'perineuronal nets'. Therefore, 'perineuronal nets' may represent sites of privileged adhesion between nerve and glial cells.

Animals↗
PubMed1993

Glutamate, GABA, calbindin-D28k and parvalbumin immunoreactivity in the pulvinar-lateralis posterior complex of the cat: relation to the projection to the Clare-Bishop area.

Neurons of the pulvinar-lateralis posterior complex (Pul-LP) containing glutamate (Glu) and GABA, as presumed neurotransmitters, and calbindin- D28k (calbindin) and parvalbumin (PV), as Ca-binding proteins, were identified in the cat by using immunohistochemical methods. In vibratome sections, neurons immunoreactive (IR) to each of the four antibodies were observed throughout the Pul-LP. In semithin sections, GABA-IR neurons were also PV-IR but not calbindin-IR and some of them also co-localized Glu. The Glu-IR neurons which were negative for GABA co-localized calbindin but not PV. The neurons of the Pul-LP projecting to the Clare-Bishop area (CB) in the suprasylvian gyrus were identified with a retrogradely transported tracer and the sections were then immunostained for Glu, GABA, calbindin and PV. Only Glu- and calbindin-IR neurons were retrogradely labeled. These results show that, if calbindin and PV have a Ca-binding role, the presumably excitatory Glu-IR neurons projecting to the CB are use calbindin whereas the presumably inhibitory GABA-IR neurons are intrinsic and use PV. This relationship implies that these proteins probably have other roles specifically related to the kind of agonist to be released at the neuron.

Animals↗
PubMed1994

Regional difference in the distribution of parvalbumin-containing neurons immunoreactive for monoclonal antibody HNK-1 in the mouse cerebral cortex.

Using preembedding immunocytochemistry at light microscopic level, we found that, although monoclonal antibody HNK-1 selectively outlined a subpopulation of GABAergic neurons containing a specific calcium-binding protein parvalbumin (PV) in the adult mouse cerebral cortex, the proportion of HNK-1-positive cells to PV-containing cells showed prominent regional difference. In the parietal cortex, approximately 50% of PV-positive cells were HNK-1-positive whereas only approximately 10% of PV-positive cells were HNK-1-immunoreactive in the occipital and temporal cortices. There were also prominent differences in this proportion among allocortical areas. These observations indicate that the cellular composition of chemically defined subpopulations of GABAergic neurons are different from area to area in mouse cerebral cortex.

Animals↗
PubMed1995

Infrequent co-existence of nitric oxide synthase and parvalbumin, calbindin and calretinin immunoreactivity in rat pontine neurons.

Neurons in the laterodorsal tegmental nucleus (LDTg), ventrolateral dorsal tegmental nucleus (LDTgV), pedunculopontine tegmental nucleus (PPTg), lateral and medial parabrachial nuclei (LPB and MPB) were immunoreactive to brain nitric oxide synthase (NOS) or isoform I. Double-labeling experiments showed that very few NOS-containing neurons in the pons were immunoreactive to any of the three calcium-binding proteins: calbindin-D 28K (CB-IR), parvalbumin (PV-IR) and calretinin (CR-IR). These findings extend our previous observation in the neocortex and suggest that a population of central NOS-containing neurons can be neurochemically characterized as CB/CR/PV deficient.

Amino Acid Oxidoreductases↗
PubMed1996

Distribution of parvalbumin immunoreactivity in the neocortex of hypothyroid adult rats.

Early hypothyroidism produces a generalized damage in the brain and in particular, changes in the connectivity of neocortical sensory areas. In this paper, the potential alterations in local neocortical circuits have been explored using immunocytochemistry for parvalbumin (PV) in normal and hypothyroid adult rats. The number and radial distribution of PV-positive cells were similar in both groups, but in hypothyroid rats, the density of PV-positive terminal-like puncta and processes was dramatically reduced, especially in layers II-III and the lower part of layers IV-V and VI. These results suggest that thyroid hormones are necessary for normal development of cortical circuits in which PV-positive cells are involved.

Animals↗
PubMed1995

Synchronous development of pyramidal neuron dendritic spines and parvalbumin-immunoreactive chandelier neuron axon terminals in layer III of monkey prefrontal cortex.

Postnatal development of the primate cerebral cortex involves an initial proliferation and the subsequent attrition of cortical synapses. Although these maturational changes in synaptic density have been observed across the cortical mantle, little is known about the precise time course of developmental refinements in synaptic inputs to specific populations of cortical neurons. We examined the postnatal development of two markers of excitatory and inhibitory inputs to a subpopulation of layer III pyramidal neurons in area 9 and 46 of rhesus monkey prefrontal cortex. These neurons are of particular interest because they play a major role in the flow of information both within and between cortical regions. Quantitative reconstructions of Golgi-impregnated mid-layer III pyramidal neurons revealed substantial developmental changes in the relative density of dendritic spines, the major site of excitatory inputs to these neurons. Relative spine density on both the apical and basilar dendritic trees increased by 50% during the first two postnatal months, remained at a plateau through 1.5 years of age, and then decreased over the peripubertal age range until stable adult levels were achieved. As a measure of the postnatal changes in inhibitory input to the axon initial segment of these pyramidal neurons, we determined the density of parvalbumin-immunoreactive axon terminals belonging to the chandelier class of local circuit neurons. The density of these distinctive axon terminals (cartridges) exhibited a temporal pattern of change that exactly paralleled the changes in dendritic spine density. These results suggest that subpopulations of cortical neurons may be regulated by dynamic interactions between excitatory and inhibitory inputs during development and, in concert with other data, they emphasize the cellular specificity of postnatal refinements in cortical circuitry.

Aging↗
PubMed1989

Parvalbumin- and calbindin D28k-immunoreactive neurons in the superficial layers of the spinal cord dorsal horn of rat.

Immunohistochemical techniques were utilized to investigate the distribution and morphology of neurons containing the calcium binding proteins parvalbumin (PV) and calbindin D28k (CaBP) in the superficial layers of rat spinal cord. Most PV-immunoreactive (PV-IR) neurons were restricted to a 25 to 60 microns thick band straddling the border between lamina II and III. Positive somata had long rostrocaudally oriented dendrites confined to narrow sagittally arranged sheets within this band and axons that entered lamina II or the superficial portions of lamina III. Long varicose axons, presumed to originate from these cells, were moderately distributed in Lissauer's tract and lamina II. CaBP-immunoreactive (CaBP-IR) neurons were found within lamina I and throughout lamina II. Large calibre PV-IR and CaBP-IR axons were seen in the dorsal column and the lateral funiculus. Dorsal rhizotomy or neonatal capsaicin treatment appeared to have no effect on PV-IR and CaBP-IR elements in the superficial lumbar dorsal horn. However, dorsal rhizotomy reduced the number of positive axons in the dorsal column and in deeper lamina of the dorsal horn. These results add to the known lamination patterns of the superficial dorsal horn and point to the existence of a lamina defined by PV-positive neurons at the lamina II/III border. These neurons may have electrophysiological characteristics attributed to PV- or CaBP-containing neurons elsewhere in the CNS.

Animals↗