Advances of Squamata astroglia to other reptiles : numerous astrocytes and glial fibrillary acidic protein (GFAP)-free areas : a preliminary study

Squamata are diapsid reptiles. Testudines were positioned formerly to the most ancient group, Anapsida, but recently they are also classified as diapsid reptiles, although their position within this group is uncertain. The investigated species of this study involved lizards (Timon tanginatus, Lacertidae; Pogona vitticeps, Agamidae; Eublepharis macularis, Gekkota; Chameleo calypratus, Chameleonidae), snakes (Epicrates cenchria maurus, Boidae; Python regius, Pythonidae; Pantherophis guttata and P. obsoletus quadrivittatus, Colubridae), and turtles (Testudo hermanni, Testudinidae; Trachemys scripta and Mauremyssinensis, Emydidae; Pelomedusa subrufa, Pleurodira). They were overanasthetised with Nembutal and transcardially perfused with 4% buffered paraformaldehyde. Coronal sections were processed according to the immunoperoxidase protocol. Monoclonal anti-GFAP and other glial markers were used. The main astroglia were the radial ependymoglia. There were two principal advances in Squamata. First, astrocytes were frequent in several areas, although, nowhere predominated. Furthermore, considerable GFAP-poor areas were found. They were extended in Python, and in Pogona and Chamaeleo GFAP was almost missing throughout the brain. The Squamata share more common astroglial features with birds than the turtles, although, represents a separate branch (Lepidosauria versus Archosauria). In mammals and birds the GFAP-free areas are usually advanced, expanded and plastic ones. Note that Squamata display quite complex behavioural phenomena related to other reptiles

Phenotype-dependent Ca2+ dynamics in single boutons of various anatomically identified GABAergic interneurons in the rat hippocampus

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Altered irisin/BDNF axis parallels excessive daytime sleepiness in obstructive sleep apnea patients

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A nemszinaptikus nikotinikus acetilkolin és NMDA receptorok szerepe élettani körülmények között és pathológiás állapotokban = Role of nonsynaptic nicotinic acetylcholine receptors and NMDA receptors in physiological and pathophysiological conditions

A szélütés (stroke) utáni neurodegeneráció a jelenlegi morbiditási és mortalitási mutatók egyik legfontosabb tényezője. Az iszkémiás stroke kezelésében számos ígéretes gyógyszerjelölt molekula vallott kudarcot a klinikai vizsgálatokban. Ennek valószínűleg az az oka, hogy hiányosak ismereteink az iszkémiás kórképek kialakulásának mechanizmusaira vonatkozólag. A legtöbb központi idegrendszerre ható gyógyszert szinaptikusan elhelyezkedő receptorokra vagy transzporterekre fejlesztik annak érdekében, hogy igazán hatékony gyógyszereket tudjunk fejleszteni, figyelembe kell venni, hogy az extraszinaptikus receptorok és transzporterek száma jóval meghaladja a szinaptikusakét, illetve hogy nagyon sok központi idegrendszeri megbetegedés alapja a nemszinaptikus rendszer malfunkciója. Például, a szinaptikus NMDA receptorok aktivációja neuroprotektív hatást fejt ki, míg az extraszinaptikus NMDA receptor aktiváció excitotoxikus hatású. Konkrét javaslataink a gyógyszerfejlesztést illetően: Az NR2B alegységet tartalmazó NMDA receptorok szelektív gátlói (mint például a fluoxetine), és a nátriumcsatorna gátlók egyes típusai; mint neuroprotektív szerek. A nikotinikus agonisták pozitív modulátorai, amelyek a kognitív problémák kezelésében, ill. a dohányzásról való leszokás segítésében lehetnek hasznosak. | Neurodegeneration after a stroke is one of the major causes of present-day morbidity and mortality. There is a long list of neuroprotective compounds that have failed to be clinically useful in the treatment of ischaemic stroke. This is likely due, at least in part, to our inadequate knowledge regarding the core mechanisms of ischaemic diseases. Most “novel” drugs that target the CNS are designed to act on neurotransmitter receptors or transporters that are localised within synapses. To develop the most effective drugs, it is important to remember that there are extrasynaptic receptors and transporters that may outnumber those located within synapses and that, when malfunctioning, may be responsible for several symptoms of CNS disorders. For example, activation of synaptic NMDA receptors is neuroprotective, whereas stimulation of extrasynaptic NMDA receptors causes excitotoxicity. We suggest that future drug development research consider the following: Compounds that are able to selectively inhibit non-synaptic NR2B Glu receptors (such as Fluoxetine), and specific subtypes of sodium channel inhibitors as neuroprotective compounds. Positive modulators of nicotinic acetylcholine receptors. They would be potential drugs in the treatment of memory problems and in smoking cessation

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks

An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ∼0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain

25 Years of Self-organized Criticality: Concepts and Controversies

Introduced by the late Per Bak and his colleagues, self-organized criticality (SOC) has been one of the most stimulating concepts to come out of statistical mechanics and condensed matter theory in the last few decades, and has played a significant role in the development of complexity science. SOC, and more generally fractals and power laws, have attracted much comment, ranging from the very positive to the polemical. The other papers (Aschwanden et al. in Space Sci. Rev., 2014, this issue; McAteer et al. in Space Sci. Rev., 2015, this issue; Sharma et al. in Space Sci. Rev. 2015, in preparation) in this special issue showcase the considerable body of observations in solar, magnetospheric and fusion plasma inspired by the SOC idea, and expose the fertile role the new paradigm has played in approaches to modeling and understanding multiscale plasma instabilities. This very broad impact, and the necessary process of adapting a scientific hypothesis to the conditions of a given physical system, has meant that SOC as studied in these fields has sometimes differed significantly from the definition originally given by its creators. In Bak’s own field of theoretical physics there are significant observational and theoretical open questions, even 25 years on (Pruessner 2012). One aim of the present review is to address the dichotomy between the great reception SOC has received in some areas, and its shortcomings, as they became manifest in the controversies it triggered. Our article tries to clear up what we think are misunderstandings of SOC in fields more remote from its origins in statistical mechanics, condensed matter and dynamical systems by revisiting Bak, Tang and Wiesenfeld’s original papers