Effects of the venom of the brown bullhead catfish (Ameiurus nebulosus) on isolated smooth muscles

Aqueous extract of the spines of the brown bullhead catfish (Ameiurus nebulosus Lesueur, 1819) caused contraction of the guinea-pig small intestine in vitro, a widely-used preparation in pharmacology. The action is dependent on extracellular Ca2+, and probably takes place on the smooth muscle cells. Mouse gastrointestinal preparations were also contracted by the extract. Stings by the spines of this fish species causes a painful sensation in man. We tested the effect of an extract of spines in isolated organ experiments on innervated smooth muscle preparations. In the guinea-pig ileum, the response to the extract was abolished by the Ca2+-channel blocker nifedipine, but only slightly reduced by atropine (a muscarine receptor antagonist) or tetrodotoxin (TTX; a blocker axonal conduction) or antagonists for P2X purinoceptors. Blocking of serotonin or histamine H1 receptors, tachykinin NK1 receptors, functional impairment of capsaicin-sensitive sensory nerve endings or inhibition of cyclo-oxygenases failed to influence the contractile effect of the extract. No inhibitory action of the extract was detected on the ileum subject to electrical motor nerve stimulation

Dual Excitatory and Smooth Muscle-relaxing Effect of Sideritis montana L. Extract on Guinea-pig Ileum

The neuronal and smooth muscle effects of methanol extract prepared from the air-dried flowering aerial parts of Sideritis montana L. (SEM) was tested in vitro on guinea-pig ileum. The chemical composition of the investigated extract was analysed by HPLC-MS, and chrysoeriol, chlorogenic acid and caffeic acid were detected as main constituents. The isolated organ assay showed that S. montana extract caused an immediate contraction and a more slowly developing inhibitory response in the ileum. The SME-induced contractions were strongly inhibited by the acetylcholine muscarinic receptor antagonist atropine (0.5 µM), but not by the Na+ channel blocker tetrodotoxin (TTX; 0.5 µM) or the histamine H1 receptor antagonist chloropyramine (0.5 µM). Selective desensitization of capsaicin-sensitive neurons by the sensory neuron stimulant and blocker capsaicin did not influence the contractile effect of SME. As to the spasmolytic effect, SME inhibited the effects of electrical field stimulation, exogenous acetylcholine, or histamine. These smooth muscle-relaxing effects were reversible by repeated renewals of the bathing solution in 40 min

UP-DOWN cortical dynamics reflect state transitions in a bistable network

In the idling brain, neuronal circuits transition between periods of sustained firing (UP state) and quiescence (DOWN state), a pattern the mechanisms of which remain unclear. Here we analyzed spontaneous cortical population activity from anesthetized rats and found that UP and DOWN durations were highly variable and that population rates showed no significant decay during UP periods. We built a network rate model with excitatory (E) and inhibitory (I) populations exhibiting a novel bistable regime between a quiescent and an inhibition-stabilized state of arbitrarily low rate. Fluctuations triggered state transitions, while adaptation in E cells paradoxically caused a marginal decay of E-rate but a marked decay of I-rate in UP periods, a prediction that we validated experimentally. A spiking network implementation further predicted that DOWN-to-UP transitions must be caused by synchronous high-amplitude events. Our findings provide evidence of bistable cortical networks that exhibit non-rhythmic state transitions when the brain rests

Magasabbrendű talamikus magvak serkentő és gátló kontrollja = Excitatory and inhibitory control of higher order thalamic nuclei

Az OTKA pályázat során leírtunk és karakterizáltunk egy új gátlás-típust a talamuszban. E gátlórendszer axonvégződései és az általuk közvetített gátlás különbözött a talamuszban jól ismert gátlórendszerek tulajdonságaitól. Az axonterminálisok ultrastruktúrája és az általuk beidegzett célelemek hatékony gátlásra utaltak. Élettani kísérletek igazolták az anatómiai predikciókat és kimutatták, hogy ez a gátlás típus hatékony információ átvitelre képes magas frekvenciás impulzusok esetén is, mikor az ismert gátlópálya hatékonysága jelentősen csökken. Az új gátlás-típus képes megakadályozni a beidegzett talamikus sejtek működését, illetve képes kiváltani a karaterisztikus visszacsapó választ. Az új gátlás-típust sikerült azonosítani több pálya esetén, köztük főemlősökben a Parkinson-kórban érintett talamikus bemenetek esetében is. A pályázat során részletesen vizsgáltuk az új gátló pálya eredő sejtjeinek szerkezetét és működését. Egy új gátlópálya leírása, melyet egyedi működési mechanizmusok jellemeznek felveti a lehetőségét e pálya szelektív modulációjának. Olyan drogok, melyek ezen a speciális gátlóterminálison hatnak segíthetnek azon tünetek enyhítésén, melyeket e pályák aberráns aktivitása okoz (pl. Parkinson-kór, krónikus fájdalom). | During the OTKA project we discovered and characterized a novel inhibitory element in the thalamus. The structure of the nerve endings, their mode of action and the activity of the nerve cells were all different from the previously described inhibitory pathways in this brain centre. The anatomy of the nerve terminals and the nerve elements they contacted indicated powerful inhibitory action. Physiological measurements verified the anatomical predictions and demonstrated that these connections faithfully transfer inhibitory signals even at very high frequency, when the effectiveness of other inhibitory pathways is much reduced. We demonstrated that these inhibitory inputs are indeed able to silence thalamic neurons or induce strong, so-called, ?postinhibitory rebound? activity. The morhology and the actvity of the parent cells of these pathways has also been extensively characterized. We described several of these pathways in different thalamic nuclei most importantly in those known to be involved in Parkinson's disease. Discovering a separate class of inhibitory pathways in the thalamus with distinct mode of action raises the hope for their selective modulation. Drugs which acts on these terminals can help to alleviate the symptoms linked to the aberrant activity of these specialized inhibitory pathways

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate

Infrared neural stimulation and inhibition using an implantable silicon photonic microdevice

Brain is one of the most temperature sensitive organs. Besides the fundamental role of temperature in cellular metabolism, thermal response of neuronal populations is also significant during the evolution of various neurodegenerative diseases. For such critical environmental factor, thorough mapping of cellular response to variations in temperature is desired in the living brain. So far, limited efforts have been made to create complex devices that are able to modulate temperature, and concurrently record multiple features of the stimulated region. In our work, the in vivo application of a multimodal photonic neural probe is demonstrated. Optical, thermal, and electrophysiological functions are monolithically integrated in a single device. The system facilitates spatial and temporal control of temperature distribution at high precision in the deep brain tissue through an embedded infrared waveguide, while it provides recording of the artefact-free electrical response of individual cells at multiple locations along the probe shaft. Spatial distribution of the optically induced temperature changes is evaluated through in vitro measurements and a validated multi-physical model. The operation of the multimodal microdevice is demonstrated in the rat neocortex and in the hippocampus to increase or suppress firing rate of stimulated neurons in a reversible manner using continuous wave infrared light (λ = 1550 nm). Our approach is envisioned to be a promising candidate as an advanced experimental toolset to reveal thermally evoked responses in the deep neural tissue

Nitrogén-monoxid, neuropeptidek és más nem-adrenerg, nem-cholinerg átvivőanyagok szerepe zsigeri funkciókban, gyógyszeres befolyásolásuk ép és gyulladásos körülmények közt = Role of nitric oxide, neuropeptides and other non-adrenergic, non-cholinergic mediators in visceral functions; their modulation by drugs under normal and inflammatory conditions

A vállalt munka fő céljai: Izolált szervi kísérletekben megismerni a zsigerek mozgásválaszainak mechanizmusait, az állatokon kapott eredményeket humán preparátumokkal összevetve. Szenzoros és más eredetű nem-adrenerg, nem-kolinerg (NANC) transzmitterek azonosítása (funkcionális vizsgálatok és a transzmitter-felszabadulás mérése). Kóros zsigeri működések modellezése. (Egyes irányokban komplett, másokban tájékozódó kísérletek). Közölt eredmények: Új humán adatok közlése mellett összefoglaltuk a kapszaicin zsigeri hatásaival, transzmittereivel kapcsolatos jelentősebb eredményeket. Alappal fölvetettük annak lehetőségét, hogy emberben?és bizonyos állatfajokban is?az NO szenzoros transzmitter (Barthó et al. 2004?Eur J Pharmac; Benkó et al. 2005?Life Sci). Mind állati, mind (világelsőként) humán GI preparátumokban bizonyítottuk az ATP közvetítő szerepét NANC válaszokban (Undi et al. 2005?Bas Clin Pharmac; 2006?Brain Res Bull; Benkó et al 2006?NS Arch Pharmac, 2007?Neurosci). Nem találtunk bizonyítékot VIP szerepére emberi bél kapszaicinnel kiváltott gátló válaszában, a CO szerepére perisztaltikus reflexben (kongresszusi közlés), ill a CO szerepére a NANC gátló válaszban állati és humán GI preparátumokon (ld. fenti közlemények). Közlésre vár: P-anyag és CGRP-IR felszabadulás bélből; szenzoros izgató mustárolaj és H2S hatásmechanizmusa; a passzív szenzibilizáció/antigén-expozíció hatásainak elemzése állati és emberi GI és légúti simaizomzaton stb. | Aims of the project Experiments on isolated tissues for elucidating the mechanisms behind some evoked movements of viscera of animals and man. Identifying sensory and other non-adrenergic, non-cholinergic (NANC) transmitters. Measuring neurotransmitter release. Modelling pathophysiological processes of viscera. (Planned were complete series of experiments in some and pilot experiments in other directions.) Published results Review, containing original results, on visceral effects of capsaicin and the transmitters thereof. Providing indirect evidence that NO is a sensory neurotransmitter (Bartho et al. 2004?Eur J Pharmac; Benko et al. 2005?Life Sci). Proving the presence of purinergic innervation of human (Undi et al. 2006?Brain Res Bull; Benko et al. 2007?Neurosci) and rat intestine (Benko et al. 2006?NS Arch Pharmac). No evidence for a mediating role of VIP in the inhibitory effect of capsaicin in the human gut, a role of CO in the peristaltic reflex (congress presentations) or in the evoked NANC relaxation in animal or human GI preparations (papers as above). To be published Release of substance P- or CGRP-like IR from the gut; mechanisms of action of the sensory stimulants mustard oil and H2S; effects of passive sensitization/antigen exposure on GI and respiratory smooth muscles of animals and man, etc