Aging somatosensory cortex displays increased density of WFA-binding perineuronal nets associated with GAD-negative neurons.

The mechanisms of aging in the brain and the subsequent decrease in cognitive abilities remain elusive. While most studies refer to research conducted in old and senile animals, little is known about the early symptoms of normal, healthy aging. In this study, we examined whether perineuronal nets (PNNs), a special form of extracellular matrix (ECM) tightly associated with neurons that is thought to be involved in limiting neuronal plasticity, undergo changes in density during early aging.

Comparison of matrix metalloproteinase activation after focal cortical ischemia in young adult and aged mice.

Matrix metalloproteinase (MMP) activity is implicated in the degradation of the extracellular matrix during cerebral ischemia. Although many studies have demonstrated spatiotemporal patterns of activation of gelatinases (MMP-9 and MMP-2) after ischemic stroke in young adult rodents, no data exist on MMP activity in old brains. In this study, we investigated the gelatinolytic activity in young adult (3-month-old) and aged (1-year-old) mice subjected to photothrombotic stroke.

Disturbance of perineuronal nets in the perilesional area after photothrombosis is not associated with neuronal death.

Perineuronal nets (PNNs) are a condensed form of extracellular matrix that covers the surface of a subset of neurons. Their presence limits neuronal plasticity and may protect neurons against harmful agents. Here we analyzed the relationship between spatiotemporal changes in PNN expression and cell death markers after focal cortical photothrombotic stroke in rats.

Matrix metalloproteinase inhibition counteracts impairment of cortical experience-dependent plasticity after photothrombotic stroke.

Matrix metalloproteinases (MMPs) are fine modulators of brain plasticity and pathophysiology. The inhibition of MMPs shortly after ischaemic stroke reduces the infarct size and has beneficial effects on post-stroke behavioural recovery. Our previous studies have shown that photothrombotic cortical stroke disrupts use-dependent plasticity in the neighbouring cortex.

Effect of focal cerebral ischaemia on modulatory neurotransmitter receptors in the rat brain: an autoradiographic study.

Neurotransmission is strongly affected after ischaemic insult. It is postulated that modulatory neurotransmitter systems and their receptors play a role in experience-dependent and restoration plasticity. In this study, muscarinic cholinergic, serotonergic 5-HT(2A/2C), dopaminergic D(1) and noradrenergic beta(1) receptors were examined after focal cerebral ischaemia in different brain regions, using quantitative in vitro autoradiography.

Parvalbumin-containing neurons, perineuronal nets and experience-dependent plasticity in murine barrel cortex.

The ability to undergo experience-dependent plasticity in the neocortex is often limited to early development, but also to particular cortical loci and specific experience. In layers II-IV of the barrel cortex, plasticity evoked by removing all but one vibrissae (univibrissa rearing) does not have a time limit except for layer IV barrels, where it can only be induced during the first postnatal week. In contrast, deprivation of every second vibrissa (chessboard deprivation) removes time limits for plasticity.

Diverse functions of perineuronal nets.

Perineuronal nets represent well-organised components of the extracellular matrix, which are surrounding cell bodies, dendrites, and axon segments of a particular class of neurones as well as forming lattice-like structures. The role of perineuronal nets is not fully elucidated yet. Perineuronal nets may play a beneficial role by stabilizing the extracellular milieu assuring the characteristic features of enveloped neurons and protecting them from the influence of harmful agents.

Exercise-induced motor improvement after complete spinal cord transection and its relation to expression of brain-derived neurotrophic factor and presynaptic markers.

Background: It has been postulated that exercise-induced activation of brain-derived neurotrophic factor (BDNF) may account for improvement of stepping ability in animals after complete spinal cord transection. As we have shown previously, treadmill locomotor exercise leads to up-regulation of BDNF protein and mRNA in the entire neuronal network of intact spinal cord. The questions arise: (i) how the treadmill locomotor training, supplemented with tail stimulation, affects the expression of molecular correlates of synaptic plasticity in spinal rats, and (ii) if a response is related to BDNF protein level and distribution.

Associative pairing involving monocular stimulation selectively mobilizes a subclass of GABAergic interneurons in the mouse visual cortex.

Levels of gamma-aminobutyric acid (GABA) and its synthesizing enzyme in cerebral cortex are regulated by sensory experience. Previously we found that associative pairing of vibrissae stimulation and tail shock results in upregulation of GABAergic markers in the mouse barrel cortex. In order to ascertain whether GABAergic upregulation also accompanies associative pairing in other sensory modalities, we examined the mouse visual cortex after analogous training with visual stimulus.

Spatiotemporal dynamics of astroglial and microglial responses after photothrombotic stroke in the rat brain.

The effects of photothrombotic stroke in primary somatosensory cortex on astroglial and microglial activation in various regions of lesioned brain were examined at different time points, using immunohistochemistry and lectin binding. The increase in GFAP expression was observed exclusively in the ipsilateral hemisphere, both in the perilesional area and cortical regions distant from the infarct. This remote increase was detectable up to sixty days after the infarct.

Vesicular glutamate transporters (VGLUTs): the three musketeers of glutamatergic system.

Glutamate is the predominant excitatory neurotransmitter in the central nervous system (CNS) and glutamatergic transmission is critical for controlling neuronal activity. Glutamate is stored in synaptic vesicles and released upon stimulation. The homeostasis of glutamatergic system is maintained by a set of transporters present in plasma membrane and in the membrane of synaptic vesicles.

Vesicular glutamate transporters VGLUT1 and VGLUT2 in the developing mouse barrel cortex.

Three vesicular glutamate transporters have been identified in mammals. Two of them, VGLUT1 and VGLUT2, define the glutamatergic phenotype and their distribution in the brain is almost complementary. In the present study we examined the distribution and expression levels of these two VGLUTs during postnatal development of the mouse barrel cortex.

Increase in synaptic hippocampal zinc concentration following chronic but not acute zinc treatment in rats.

Electroconvulsive seizures (ECS), one of the most effective treatments of depression, induce mossy fiber sprouting (when assayed by means of synaptic zinc method), and this indicates an increase in the synaptic zinc level in the hippocampus following such therapy. The aim of the present study was to investigate the influence of acute and chronic zinc hydroaspartate administration on the synaptic and total zinc level in the rat hippocampus. We used two methods of zinc determination: (1) zinc-selenium method, which images the pool of synaptic zinc, and (2) flame atomic absorption spectrometry, which assays the total concentration of zinc.

Dissociation of synaptic zinc level and zinc transporter 3 expression during postnatal development and after sensory deprivation in the barrel cortex of mice.

In the neocortex, synaptic zinc level is regulated by sensory experience. Previously, we found that trimming of mystacial vibrissae resulted in an increase of synaptic zinc level in corresponding deprived barrels in the cortex of mice. The present study focused on the relationship between synaptic zinc and zinc transporter 3 (ZnT3) protein expression in the barrel cortex of mice during postnatal development and after sensory deprivation of selected vibrissae.

D1 dopamine receptors distribution following photothrombotic stroke in rat cerebral cortex.

The effect of focal photothrombotic stroke on the distribution of D1 dopamine receptor (D1R) sites was examined in different cortical areas of rat brain with quantitative receptor autoradiography using [3H]SCH23390 as a ligand. Unilateral cortical stroke was located in the primary somatosensory cortex. After different survival times (1, 7 and 28 days) D1R binding levels were determined in the lesion core, penumbra, frontoparietal motor (FrPaM) and somatosensory (FrPaSS) areas as well as in homotopic regions in the contralateral hemisphere.

A surface antigen delineating a subset of neurons in the primary somatosensory cortex of the mouse.

Synapsins are a family of proteins associated with synaptic vesicles that are widely used as markers of synaptic terminals. We decided to investigate synapsin I expression in the mouse primary somatosensory cortex (SI). Immunostaining experiments using a polyclonal antibody against C-terminal domain of synapsin Ia/b (anti-SynI-C) showed an unusual pattern in the SI cortex compared to other regions of the neocortex.

Switch time-point for rapid experience-dependent changes in zinc-containing circuits in the mouse barrel cortex.

It has been previously demonstrated that in the mouse barrel cortex, synaptic zinc is regulated by sensory experience. In adult mice, cutting selected vibrissae produced a rapid but transient elevation of synaptic zinc in the corresponding barrels several hours later, whereas in 8 day-old animals this procedure did not affect synaptic zinc. In the present study, we wished to determine the postnatal age at which zinc-containing terminals gain the ability to respond rapidly to a restriction of sensory input.

Differential response of synaptic zinc levels to sensory deprivation in the barrel cortex of young and adult mice.

The distribution of synaptic zinc after short-term (up to 48 h) tactile deprivation of vibrissae was investigated in the barrel cortex of mice using histochemical staining. In adult mice, 12 h after trimming selected rows of vibrissae, an increase in zinc staining in the deprived barrels was observed. This increase was still present 48 h after trimming.

Deprivation and denervation differentially affect zinc-containing circuitries in the barrel cortex of mice.

In the neocortex, a population of glutamatergic synapses contains chelatable zinc that is released upon depolarization. The present study compares the effect of chronic tactile deprivation and vibrissectomy performed at different postnatal ages on the synaptic zinc distribution in the mouse barrel cortex. We found that a chronic unilateral tactile deprivation resulted in an increase of synaptic zinc in deprived barrels.

Differences between rats and rabbits in NMDA receptor-mediated calcium signalling in hippocampal neurones.

In vivo microdialysis combined with the measurement of (45)Ca(2+) efflux from prelabelled hippocampus demonstrated a pronounced N-methyl-D-aspartate (NMDA)-evoked (45)Ca(2+) release to the dialysate in the rat dentate gyrus (DG) and CA1, whereas in rabbit a slight release of (45)Ca(2+) was observed only in the DG. In vitro, we noticed that the NMDA-evoked increase in Fura-2 detected intracellular Ca(2+) concentration in synaptoneurosomes from the rat, but not from the rabbit hippocampus, was strongly inhibited by the ryanodine receptor (RyR) antagonists dantrolene and ryanodine. To establish the mechanism of these differences, we characterised their possible dependence on the expression of RyR and their co-localisation with the calcium binding protein calbindin D(28k).

NMDA-induced 45Ca release in the dentate gyrus of newborn rats: in vivo microdialysis study.

This in vivo study, aimed at detecting the N-methyl-D-aspartate (NMDA) evoked Ca(2+)-induced Ca(2+) release from intracellular stores in the neonatal rat brain, demonstrates that the application of 5 mM N-methyl-D-aspartate via a microdialysis probe for 20 min to the dentate gyrus (DG) of halotane-anesthetized 7 day-old (postnatal day 7, PND 7) rats induces a prolonged decrease in Ca(2+) concentration in an initially calcium-free dialysis medium, indicative of a drop in the extracellular concentration of Ca(2+) and Ca(2+) influx to neurons. In parallel experiments, a huge NMDA-evoked release of 45Ca from the pre-labeled endogenous Ca(2+) pool was observed and interpreted as the expression of intracellular Ca(2+) release. Dantrolene (100 microM) significantly inhibited the NMDA-induced 45Ca release, whereas 250 microM ryanodine exerted an unspecific biphasic effect.

Phosphorylated MAP-1B isoforms in the developing mouse barrel cortex.

Developmental expression of two phosphorylation modes of microtubule-associated protein 1B (MAP-1B) has been studied in the barrel cortex of mice at postnatal days (P)5, P12, P21 and P90 using immunocytochemistry with antibodies 125 and 150 that recognize phosphorylation modes II and I, respectively. The antibody 125 immunoreactive processes, identified as dendrites, are not yet detectable at P5; they are already present at P12 and become more evident at P21. In the barrel cortex of P90 animals the antibody 125 immunopositive dendrites are still present, although they are much less pronounced.

Deafferentation induced changes in GAD67 and GluR2 mRNA expression in mouse somatosensory cortex.

Partial vibrissectomy in adult mice induces body map plasticity in SI barrel cortex. To examine if the disturbed balance of cortical activation affects the excitatory and inhibitory neurotransmitter systems, we studied glutamic acid decarboxylase (GAD 67) and AMPA receptor subunit GluR2 mRNA expression in the barrel cortex. At varying times post-vibrissectomy, sparing row C of whiskers on one side of the snout, the brains were processed for in situ hybridization using specific [(35)S]oligonucleotides to detect the laminar localization of GAD67 and GluR2 mRNAs.

Partial blocking of NMDA receptors reduces plastic changes induced by short-lasting classical conditioning in the SI barrel cortex of adult mice.

The effect of blockade of N-methyl-D-aspartate (NMDA) receptors in the barrel cortex upon the learning-induced changes of the cortical body map was examined in adult mice. We have previously found that three sensory conditioning sessions, in which stimulation of a row of vibrissae was paired with a tail shock, produced an enlargement of the functional representation of a row of vibrissae stimulated during training. Implantation of the slow release polymer Elvax, containing 2-amino-5-phosphonovalerate (APV, 50 mM), in the vicinity of the barrel cortex was performed 1 day before conditioning to block NMDA receptors.