parvalbumin interneurons Dotaz Zobrazit nápovědu
The retrosplenial cortex (RSC) is a mesocortical region broadly involved with memory and navigation. It shares many characteristics with the perirhinal cortex (PRC), both of which appear to be significantly involved in the spreading of epileptic activity. We hypothesized that RSC possesses an interneuronal composition similar to that of PRC. To prove the hypothesis we studied the general pattern of calretinin (CR) and parvalbumin (PV) immunoreactivity in the RSC of the rat brain, its optical density as well as the morphological features and density of CR- and PV-immunoreactive (CR+ and PV+) interneurons. We also analyzed the overall neuronal density on Nissl-stained sections in RSC. Finally, we compared our results with our earlier analysis of PRC (Barinka et al., 2012). Compared to PRC, RSC was observed to have a higher intensity of PV staining and lower intensity of CR staining of neuropil. Vertically-oriented bipolar neurons were the most common morphological type among CR+ neurons. The staining pattern did not allow for a similarly detailed analysis of somatodendritic morphology of PV+ neurons. RSC possessed lower absolute (i.e., neurons/mm(3)) and relative (i.e., percentage of the overall neuronal population) densities of CR+ neurons and similar absolute and lower relative densities of PV+ neurons relative to PRC. CR: PV neuronal ratio in RSC (1:2 in area 29 and 1:2.2 in area 30) differed from PRC (1:1.2 in area 35 and 1:1.7 in area 36). In conclusion, RSC, although similar in many aspects to PRC, differs strikingly in the interneuronal composition relative to PRC.
- Klíčová slova
- Calcium-binding proteins, Calretinin, Interneurons, Parvalbumin, Perirhinal cortex, Retrosplenial cortex,
- MeSH
- analýza rozptylu MeSH
- denzitometrie MeSH
- interneurony metabolismus MeSH
- kalbindin 2 metabolismus MeSH
- krysa rodu Rattus MeSH
- mozková kůra cytologie MeSH
- parvalbuminy metabolismus MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kalbindin 2 MeSH
- parvalbuminy MeSH
Finding a cure for Alzheimer's disease (AD) has been notoriously challenging for many decades. Therefore, the current focus is mainly on prevention, timely intervention, and slowing the progression in the earliest stages. A better understanding of underlying mechanisms at the beginning of the disease could aid in early diagnosis and intervention, including alleviating symptoms or slowing down the disease progression. Changes in social cognition and progressive parvalbumin (PV) interneuron dysfunction are among the earliest observable effects of AD. Various AD rodent models mimic these early alterations, but only a narrow field of study has considered their mutual relationship. In this review, we discuss current knowledge about PV interneuron dysfunction in AD and emphasize their importance in social cognition and memory. Next, we propose oxytocin (OT) as a potent modulator of PV interneurons and as a promising treatment for managing some of the early symptoms. We further discuss the supporting evidence on its beneficial effects on AD-related pathology. Clinical trials have employed the use of OT in various neuropsychiatric diseases with promising results, but little is known about its prospective impacts on AD. On the other hand, the modulatory effects of OT in specific structures and local circuits need to be clarified in future studies. This review highlights the connection between PV interneurons and social cognition impairment in the early stages of AD and considers OT as a promising therapeutic agent for addressing these early deficits.
- Klíčová slova
- Alzheimer’s disease, animal models, dementia, hippocampus, oxytocin, parvalbumin interneurons, social cognition, social memory,
- MeSH
- Alzheimerova nemoc * patologie MeSH
- hipokampus patologie MeSH
- interneurony MeSH
- kognice MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- oxytocin MeSH
- parvalbuminy metabolismus MeSH
- prospektivní studie MeSH
- sociální kognice MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- oxytocin MeSH
- parvalbuminy MeSH
Maternal immune activation (MIA) during pregnancy represents an important environmental factor in the etiology of schizophrenia and autism spectrum disorders (ASD). Our goal was to investigate the impacts of MIA on the brain and behavior of adolescent and adult offspring, as a rat model of these neurodevelopmental disorders. We injected bacterial lipopolysaccharide (LPS, 1 mg/kg) to pregnant Wistar dams from gestational day 7, every other day, up to delivery. Behavior of the offspring was examined in a comprehensive battery of tasks at postnatal days P45 and P90. Several brain parameters were analyzed at P28. The results showed that prenatal immune activation caused social and communication impairments in the adult offspring of both sexes; males were affected already in adolescence. MIA also caused prepulse inhibition deficit in females and increased the startle reaction in males. Anxiety and hypolocomotion were apparent in LPS-affected males and females. In the 28-day-old LPS offspring, we found enlargement of the brain and decreased numbers of parvalbumin-positive interneurons in the frontal cortex in both sexes. To conclude, our data indicate that sex of the offspring plays a crucial role in the development of the MIA-induced behavioral alterations, whereas changes in the brain apparent in young animals are sex-independent.
- Klíčová slova
- autism, chronic bacterial infection, development, lipopolysaccharide, macrocephaly, maternal immune activation, parvalbumin-positive interneurons, prenatal infection, schizophrenia, sex differences,
- MeSH
- chování zvířat * MeSH
- imunohistochemie MeSH
- imunomodulace * MeSH
- interneurony metabolismus MeSH
- krysa rodu Rattus MeSH
- lipopolysacharidy imunologie MeSH
- matka - expozice noxám MeSH
- mikroglie imunologie metabolismus MeSH
- mozek imunologie metabolismus MeSH
- parvalbuminy metabolismus MeSH
- sexuální faktory MeSH
- sociální chování MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipopolysacharidy MeSH
- parvalbuminy MeSH
The perirhinal cortex (PRC) composed of areas 35 and 36 forms an important route for activity transfer between the hippocampus-entorhinal cortex and neocortex. Its function in memory formation and consolidation as well as in the initiation and spreading of epileptic activity was already partially elucidated. We studied the general pattern of calretinin (CR), parvalbumin (PV) and calbindin (CB) immunoreactivity and its corrected relative optical density (cROD) as well as morphological features and density of CR and PV immunoreactive (CR+, PV+) interneurons in the rat PRC. Neighboring neocortical association area Te3V was analyzed as well. The PRC differed from the Te3V in higher CR and lower PV overall immunoreactivity level. On CR immunostained sections, the difference between high cROD value in area 35 and low cROD value in area Te3V reached statistical significance (p<0.05). The pattern of CB immunoreactivity was similar to that of the neocortex. Vertically oriented bipolar neurons were the most common morphological type of CR+ neurons, multipolar neuronal morphology was typical among PV+ neurons and vertically oriented bipolar neurons and multipolar neurons were approximately equally frequent among CB+ neurons. The density of CR+ and PV+ neurons was stereologically measured. While the density of PV+ neurons was not significantly different in PRC when compared to Te3V, density of CR+ neurons in area 35 was significantly higher by comparison with Te3V (p<0.05). Further, the overall neuronal density was measured on Nissl stained sections and the proportion of CR+ and PV+ interneurons was expressed as a percentage of the total neurons counts. The percentage of CR+ interneurons was higher in area 35 by comparison with area Te3 (p<0.05), while the percentage of PV+ interneurons did not significantly differ among the examined areas. In conclusion, the PRC possesses specific interneuronal equipment with unusually high proportion of CR+ interneurons, what might be of importance for the presumed gating function of PRC in normal and diseased states.
- MeSH
- interneurony chemie metabolismus MeSH
- kalbindin 2 MeSH
- kalbindiny MeSH
- krysa rodu Rattus MeSH
- mozková kůra chemie metabolismus MeSH
- neurony chemie metabolismus MeSH
- parvalbuminy analýza metabolismus MeSH
- S100 kalcium vázající protein G analýza metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- Calb2 protein, rat MeSH Prohlížeč
- kalbindin 2 MeSH
- kalbindiny MeSH
- parvalbuminy MeSH
- S100 kalcium vázající protein G MeSH
Schizophrenia research has increased in recent decades and focused more on its neural basis. Decision-making and cognitive flexibility are the main cognitive functions that are impaired and considered schizophrenia endophenotypes. Cognitive impairment was recently connected with altered functions of N-methyl-d-aspartate (NMDAR) glutamatergic receptors, which increased cortical activity. Selective NMDAR antagonists, such as MK-801, have been used to model cognitive inflexibility in schizophrenia. Decreased GABAergic inhibitory activity has been shown elsewhere with enhanced cortical activity. This imbalance in the excitatory/inhibitory may reduce the entrainment of prefrontal gamma and hippocampal theta rhythms and result in gamma/theta band de-synchronization. The current study established an acute MK-801 administration model of schizophrenia-like cognitive inflexibility in rats and used the attentional set-shifting task in which rats learned to switch/reverse the relevant rule. During the task, we used in vivo optogenetic stimulations of parvalbumin-positive interneurons at specific light pulses in the prefrontal cortex and ventral hippocampus. The first experiments showed that acute dizocilpine in rats produced schizophrenia-like cognitive inflexibility. The second set of experiments demonstrated that specific optogenetic stimulation at specific frequencies of parvalbumin-positive interneurons in the prefrontal cortex and ventral hippocampus rescued the cognitive flexibility rats that received acute MK-801. These findings advance our knowledge of the pivotal role of parvalbumin interneurons in schizophrenia-like cognitive impairment and may guide further research on this severe psychiatric disorder.
- Klíčová slova
- Attentional set-shifting task, Excitatory/inhibitory ratio, Gamma waves, MK-801, theta waves,
- MeSH
- dizocilpinmaleát * farmakologie MeSH
- hipokampus metabolismus MeSH
- interneurony metabolismus MeSH
- kognice MeSH
- krysa rodu Rattus MeSH
- optogenetika MeSH
- parvalbuminy metabolismus MeSH
- prefrontální mozková kůra metabolismus MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- schizofrenie * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- dizocilpinmaleát * MeSH
- parvalbuminy MeSH
- receptory N-methyl-D-aspartátu MeSH
The calcium binding protein parvalbumin (PV) in the mammalian neocortex is expressed in a subpopulation of cortical GABAergic inhibitory interneurons. PV - producing interneurons represent the largest subpopulation of neocortical inhibitory cells, exhibit mutual chemical and electrical synaptic contacts and are well known to generate gamma oscillation. This review summarizes basic data of the distribution, afferent and efferent connections and physiological properties of parvalbumin expressing neurons in the neocortex. Basic data about participation of PV-positive neurons in cortical microcircuits are presented. Autaptic connections, metabolism and perineuronal nets (PNN) of PV positive neurons are also discussed.
- MeSH
- extracelulární matrix metabolismus MeSH
- interneurony metabolismus MeSH
- neokortex * metabolismus MeSH
- neurony * metabolismus MeSH
- parvalbuminy * metabolismus MeSH
- savci metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- parvalbuminy * MeSH
The changes in density of inhibitory parvalbumin-immunoreactive interneurons were quantitatively studied by immunohistochemistry in a series of human neocortical samples comprising the spectrum of malformations of cortical development (MCD) encountered in epilepsy surgery and the non-malformed hippocampal sclerosis-temporal neocortex in patients with refractory temporal lobe epilepsy. The highest relative density of parvalbumin-immunoreactive cells was obtained in the control samples (n = 21). The number of parvalbumin-immunoreactive neurons was significantly decreased in non-malformed hippocampal sclerosis-temporal neocortex (n = 73, 80.5% of control values). In a proportion of the latter samples as well as in two controls we observed patchy regions of absence of parvalbumin staining. The total counts of parvalbumin-immunoreactive cells in all the categories of MCD - "mild MCD" (n = 25), focal cortical dysplasia type I (n = 19) and type II (n = 15) - were decreased representing 72.4%, 55.0% and 12.2% of control values, respectively. Significantly different parvalbumin-immunoreactive cell densities were demonstrated between the focal cortical dysplasia types IIA and IIB. In "mild MCD", we observed a more pronounced decrease of parvalbumin-immunoreactive cells in the infragranular layers. No significant differences were revealed between the temporal and extratemporal examples of analogous MCD types. This study provides evidence for reduction of inhibitory parvalbumin-immunoreactive interneurons in the epileptic neocortex affected by MCD as well as in morphologically unaffected epileptic temporal neocortex, thus representing a possible mechanism for their epileptogenicity.
- MeSH
- biologické markery MeSH
- diferenciální diagnóza MeSH
- dítě MeSH
- dospělí MeSH
- epilepsie temporálního laloku metabolismus patologie patofyziologie MeSH
- epilepsie metabolismus patologie patofyziologie MeSH
- glióza metabolismus patologie patofyziologie MeSH
- hipokampus abnormality metabolismus patologie MeSH
- imunohistochemie MeSH
- interneurony metabolismus patologie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- malformace nervového systému * MeSH
- mladiství MeSH
- parvalbuminy metabolismus MeSH
- počet buněk MeSH
- předškolní dítě MeSH
- spánkový lalok abnormality metabolismus patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- parvalbuminy MeSH
Exposure to loud sounds damages the auditory periphery and induces maladaptive changes in central parts of the auditory system. Diminished peripheral afferentation and altered inhibition influence the processing of sounds in the auditory cortex. It is unclear, however, which types of inhibitory interneurons are affected by acoustic trauma. Here we used single-unit electrophysiological recording and two-photon calcium imaging in anesthetized mice to evaluate the effects of acute acoustic trauma (125 dB SPL, white noise, 5 min) on the response properties of neurons in the core auditory cortex. Electrophysiological measurements suggested the selective impact of acoustic trauma on inhibitory interneurons in the auditory cortex. To further investigate which interneuronal types were affected, we used two-photon calcium imaging to record the activity of neurons in cortical layers 2/3 and 4, specifically focusing on parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons. Spontaneous and pure-tone-evoked firing rates of SST+ interneurons increased in layer 4 immediately after acoustic trauma and remained almost unchanged in layer 2/3. Furthermore, PV+ interneurons with high best frequencies increased their evoked-to-spontaneous firing rate ratios only in layer 2/3 and did not change in layer 4. Finally, acoustic trauma unmasked low-frequency excitatory inputs only in layer 2/3. Our results demonstrate layer-specific changes in the activity of auditory cortical inhibitory interneurons within minutes after acoustic trauma.
- Klíčová slova
- broadband noise, calcium imaging, inhibition, interneurons, plasticity,
- MeSH
- akční potenciály MeSH
- interneurony metabolismus fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nedoslýchavost z hluku patofyziologie MeSH
- parvalbuminy genetika metabolismus MeSH
- sluchové evokované potenciály * MeSH
- sluchové korové centrum cytologie patofyziologie MeSH
- somatostatin genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- parvalbuminy MeSH
- somatostatin MeSH
Focal cortical dysplasias (FCDs) represent a prominent cause of pharmacologically intractable epilepsy. In FCD, the decrease of parvalbumin immunoreactive (PV+) inhibitory interneurons has been repeatedly documented. Here, we wanted to show whether another interneuronal population, the calretinin immunoreactive (CR+) neurons, exhibits any change in human FCD. We also investigated samples of morphologically normal temporal neocortex resected together with sclerotic hippocampus (nHSTN), where decrease of PV+ interneurons was previously documented as well. Brain tissue from 24 patients surgically treated for pharmacoresistant epilepsy was examined. Calretinin immunoreactivity was qualitatively evaluated and the density of CR+ neuronal profiles was quantified. As a control, post-mortem acquired neocortical samples of nine patients without any brain affecting disease were used. CR+ neurons were located predominantly in superficial cortical layers both in controls and pathological samples. Similarly, the morphology of CR+ neurons was unaffected in pathological samples. The overall density of CR+ neurons was significantly decreased in FCD type I (to approximately 70% of control values) and even more in FCD type II (to approximately 50% of controls). In nHSTN, no change compared to controls was found in CR+ neuronal density. Our results may contribute to the better understanding of the role of individual interneuronal populations in epileptogenesis.
- MeSH
- dítě MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- epilepsie diagnostické zobrazování metabolismus patologie MeSH
- fluorodeoxyglukosa F18 MeSH
- hipokampus diagnostické zobrazování metabolismus patologie MeSH
- interneurony metabolismus MeSH
- kalbindin 2 MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malformace mozkové kůry diagnostické zobrazování patologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková kůra diagnostické zobrazování metabolismus patologie MeSH
- parvalbuminy metabolismus MeSH
- pozitronová emisní tomografie MeSH
- předškolní dítě MeSH
- S100 kalcium vázající protein G metabolismus MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CALB2 protein, human MeSH Prohlížeč
- fluorodeoxyglukosa F18 MeSH
- kalbindin 2 MeSH
- parvalbuminy MeSH
- S100 kalcium vázající protein G MeSH
The main aim was to describe interneuronal population expressing calcium binding proteins calretinin (CR) and parvalbumin (PV) in the perirhinal (PRC) and retrosplenial (RSC) cortex of the rat. These two cortical areas differ strikingly in their connectivity and function, which could be caused also by different structure of the interneuronal populations. Having a precise knowledge of the cellular composition of any cerebral area forms one of the basic input parameters and tenets for computational modelling of neuronal networks and for understanding some pathological conditions, like generating and spreading of epileptic activity. PRC possesses higher absolute and relative densities of CR+ and PV+ neurons than RSC, but the CR : PV ratio is higher in the RSC, which is similar to the neocortex. The bipolar/bitufted neurons are most common type of CR+ population, while the majority of PV+ neurons show multipolar morphology. Current results indicate that main difference between analysed areas is in density of CR+ neurons, which was significantly higher in the PRC. Our results coupled with works of other authors show that there are significant differences in the interneuronal composition and distribution of heretofore seemingly similar transitional cortical areas. These results may contribute to the better understanding of the mechanism of function of this cortical region in normal and diseased states.
- MeSH
- cingulární gyrus cytologie metabolismus MeSH
- imunohistochemie MeSH
- interneurony metabolismus MeSH
- kalbindin 2 metabolismus MeSH
- krysa rodu Rattus MeSH
- parvalbuminy metabolismus MeSH
- perirhinální mozková kůra cytologie metabolismus MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- Calb2 protein, rat MeSH Prohlížeč
- kalbindin 2 MeSH
- parvalbuminy MeSH