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
Visual (and probably also magnetic) signal processing starts at the first synapse, at which photoreceptors contact different types of bipolar cells, thereby feeding information into different processing channels. In the chicken retina, 15 and 22 different bipolar cell types have been identified based on serial electron microscopy and single-cell transcriptomics, respectively. However, immunohistochemical markers for avian bipolar cells were only anecdotally described so far. Here, we systematically tested 12 antibodies for their ability to label individual bipolar cells in the bird retina and compared the eight most suitable antibodies across distantly related species, namely domestic chicken, domestic pigeon, common buzzard, and European robin, and across retinal regions. While two markers (GNB3 and EGFR) labeled specifically ON bipolar cells, most markers labeled in addition to bipolar cells also other cell types in the avian retina. Staining pattern of four markers (CD15, PKCα, PKCβ, secretagogin) was species-specific. Two markers (calbindin and secretagogin) showed a different expression pattern in central and peripheral retina. For the chicken and European robin, we found slightly more ON bipolar cell somata in the inner nuclear layer than OFF bipolar cell somata. In contrast, OFF bipolar cells made more ribbon synapses than ON bipolar cells in the inner plexiform layer of these species. Finally, we also analyzed the photoreceptor connectivity of selected bipolar cell types in the European robin retina. In summary, we provide a catalog of bipolar cell markers for different bird species, which will greatly facilitate analyzing the retinal circuitry of birds on a larger scale.
- Klíčová slova
- AAV virus, European robin (Erithacus rubecula), bipolar cell, buzzard (Buteo buteo), chicken (Gallus gallus), double cone, magnetoreception, pigeon (Columba livia), retina,
- MeSH
- bipolární buňky sítnice MeSH
- čípky retiny MeSH
- elektronová mikroskopie MeSH
- kur domácí MeSH
- retina chemie MeSH
- secretagoginy * metabolismus MeSH
- synapse metabolismus MeSH
- zpěvní ptáci * MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- secretagoginy * 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
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
The olfactory system in insects has evolved to process the dynamic changes in the concentration of food odors or sex pheromones to localize the nutrients or conspecific mating partners. Experimental studies have suggested that projection neurons (PNs) in insects encode not only the stimulus intensity but also its rate-of-change (input gradient). In this study, we aim to develop a simple computational model for a PN to understand the mechanism underlying the coding of the rate-of-change information. We show that the spike frequency adaptation is a potential key mechanism for reproducing the phasic response pattern of the PN in Drosophila. We also demonstrate that this adaptation mechanism enables the PN to encode the rate-of-change of the input firing rate. Finally, our model predicts that the PN exhibits the intensity-invariant response for the pulse and ramp odor stimulus. These results suggest that the developed model is useful for investigating the coding principle underlying olfactory information processing in insects.
- Klíčová slova
- Input rate-of-change, Insect olfactory system, Sensory coding, Spike frequency adaptation,
- MeSH
- čich fyziologie MeSH
- čichové buňky * fyziologie MeSH
- čichové dráhy * fyziologie MeSH
- Drosophila MeSH
- hmyz MeSH
- interneurony MeSH
- odoranty MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Acetylcholine is an important modulator of striatal activity, and it is vital to controlling striatal-dependent behaviors, including motor and cognitive functions. Despite this significance, the mechanisms determining how acetylcholine impacts striatal signaling are still not fully understood. In particular, little is known about the role of nAChRs expressed by striatal interneurons. In the present study, we used FISH to determine which neuronal types express the most prevalent beta2 nicotinic subunit in the mouse striatum. Our data support a common view that nAChR expression is mostly restricted to striatal interneurons. Surprisingly though, cholinergic interneurons were identified as a population with the highest expression of beta2 nicotinic subunit. To investigate the functional significance of beta2-containing nAChRs in striatal interneurons, we deleted them by injecting the AAV-Cre vector into the striatum of beta2-flox/flox male mice. The deletion led to alterations in several behavioral domains, namely, to an increased anxiety-like behavior, decrease in sociability ratio, deficit in discrimination learning, and increased amphetamine-induced hyperlocomotion and c-Fos expression in mice with beta2 deletion. Further colocalization analysis showed that the increased c-Fos expression was present in both medium spiny neurons and presumed striatal interneurons. The present study concludes that, despite being relatively rare, beta2-containing nAChRs are primarily expressed in striatal neurons by cholinergic interneurons and play a significant role in behavior.SIGNIFICANCE STATEMENT A large variety of nAChRs are expressed in the striatum, a brain region that is crucial in the control of behavior. The complexity of receptors with different functions is hindering our understanding of mechanisms through which striatal acetylcholine modulates behavior. We focused on the role of a small population of beta2-containing nAChRs. We identified neuronal types expressing these receptors and determined their impact in the control of explorative behavior, anxiety-like behavior, learning, and sensitivity to stimulants. Additional experiments showed that these alterations were associated with an overall increased activity of striatal neurons. Thus, the small population of nicotinic receptors represents an interesting target for a modulation of response to stimulant drugs and other striatal-based behavior.
- Klíčová slova
- Fos, acetylcholine, behavior, interneurons, nAChRs, striatum,
- MeSH
- acetylcholin metabolismus MeSH
- cholinergní látky farmakologie MeSH
- corpus striatum metabolismus MeSH
- interneurony metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nikotinové receptory * metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- acetylcholin MeSH
- cholinergní látky MeSH
- nikotinové receptory * MeSH
Maternal immune activation has been identified as a significant risk factor for schizophrenia. Using rodent models, past work has demonstrated various behavioral and brain impairments in offspring after immune-activating events. We applied 5 mg/kg of poly(I:C) on gestation day 9 to pregnant mouse dams, whose offspring were then stressed during puberty. We show impairments in attentional set-shifting in a T-maze, and a decreased number of parvalbumin-positive interneurons in the hippocampus as a result of peripubertal stress specifically in females.
- Klíčová slova
- Behavioral tests, Cognitive deficit, Immunochallenge, Interneurons, Maternal immune activation, Mouse, Poly(I:C), Prenatal infection, Schizophrenia,
- MeSH
- chování zvířat fyziologie MeSH
- exekutivní funkce fyziologie MeSH
- hipokampus cytologie MeSH
- infekční komplikace v těhotenství * chemicky indukované imunologie MeSH
- interneurony cytologie MeSH
- kognitivní dysfunkce etiologie patologie patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- poly I-C aplikace a dávkování MeSH
- pozornost fyziologie MeSH
- psychický stres komplikace patologie patofyziologie MeSH
- schizofrenie etiologie imunologie patologie patofyziologie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované patologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- poly I-C MeSH
Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacological treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ-aminobutyric acid (GABA) could be used to counteract the imbalance between excitation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid-induced status epilepticus. Using whole-cell patch-clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic interneurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof-of-concept that hESC-derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.
- Klíčová slova
- GABA, cell integration, epilepsy, human embryonic stem cells, interneurons, optogenetics, synaptic integration,
- MeSH
- GABA metabolismus MeSH
- hipokampus metabolismus patologie MeSH
- interneurony cytologie metabolismus MeSH
- kmenové buňky cytologie metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- kyselina kainová škodlivé účinky MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- recidiva MeSH
- status epilepticus chemicky indukované metabolismus patologie terapie MeSH
- transplantace kmenových buněk metody MeSH
- záchvaty chemicky indukované metabolismus patologie terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- GABA MeSH
- kyselina kainová MeSH
In the vertebrate retina, amacrine and ganglion cells represent the most diverse cell classes. They can be classified into different cell types by several features, such as morphology, light responses, and gene expression profile. Although birds possess high visual acuity (similar to primates that we used here for comparison) and tetrachromatic color vision, data on the expression of transcription factors in retinal ganglion cells of birds are largely missing. In this study, we tested various transcription factors, known to label subpopulations of cells in mammalian retinae, in two avian species: the common buzzard (Buteo buteo), a raptor with exceptional acuity, and the domestic pigeon (Columba livia domestica), a good navigator and widely used model for visual cognition. Staining for the transcription factors Foxp2, Satb1 and Satb2 labeled most ganglion cells in the avian ganglion cell layer. CtBP2 was established as marker for displaced amacrine cells, which allowed us to reliably distinguish ganglion cells from displaced amacrine cells and assess their densities in buzzard and pigeon. When we additionally compared the temporal and central fovea of the buzzard with the fovea of primates, we found that the cellular organization in the pits was different in primates and raptors. In summary, we demonstrate that the expression of transcription factors is a defining feature of cell types not only in the retina of mammals but also in the retina of birds. The markers, which we have established, may provide useful tools for more detailed studies on the retinal circuitry of these highly visual animals.
- Klíčová slova
- amacrine cells, cell type, fovea, ganglion cells, marmoset retina, retina, starburst amacrine cells, transcription factor,
- MeSH
- amakrinní buňky chemie metabolismus MeSH
- Callithrix MeSH
- Columbidae MeSH
- druhová specificita MeSH
- retina chemie cytologie metabolismus MeSH
- transkripční faktory analýza biosyntéza genetika MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- transkripční faktory MeSH
We used two-photon calcium imaging with single-cell and cell-type resolution. Fear conditioning induced heterogeneous tuning shifts at single-cell level in the auditory cortex, with shifts both to CS+ frequency and to the control CS- stimulus frequency. We thus extend the view of simple expansion of CS+ tuned regions. Instead of conventional freezing reactions only, we observe selective orienting responses towards the conditioned stimuli. The orienting responses were often followed by escape behavior.
- MeSH
- akustická stimulace MeSH
- chování zvířat MeSH
- elektrický šok MeSH
- interneurony fyziologie MeSH
- klasické podmiňování fyziologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- neuroplasticita fyziologie MeSH
- sluchové korové centrum fyziologie MeSH
- strach psychologie MeSH
- učení fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH