bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6‐OHDA lesion model depends on the site of administration of the trophic factor
Authors: Kirik Deniz , Rosenblad Carl , Björklund Anders 
Published: March 2003

AbstractHere we studied whether glial cell line‐derived neurotrophic factor (GDNF), given as a single bolus injection before an intrastriatal 6‐hydroxydopamine (6‐OHDA) lesion, can protect the nigrostriatal dopamine neurons against the toxin‐induced damage and preserve normal motor functions in the lesioned animals. GDNF or vehicle was injected in the striatum (25 μg), substantia nigra (25 μg) or lateral ventricle (50 μg) 6 h before the 6‐OHDA lesion (20 μg/3 μL). Motor function was evaluated by the stepping and drug‐induced motor asymmetry tests. Lesioned animals given vehicle alone showed a clear ipsilateral‐side bias in response to amphetamine (13 turns/min), a moderate contralateral‐side bias to apomorphine (4.5 turns/min) and a moderate to severe stepping deficit on the contralateral forepaw (three to four steps, as compared with 11–13 steps on the unimpaired side). Injection of GDNF into the striatum had a significant protective effect both on nigrostriatal function (1–2 turns/min in the rotation tests and seven to eight steps in the stepping test), and the integrity of the nigrostriatal pathway, seen as a protection of both the cell bodies in the substantia nigra and the dopamine innervation in the striatum. Injection of GDNF in the nigra had a protective effect on the nigral cell bodies, but not the striatal innervation, and failed to provide any functional benefit. In contrast, intranigral GDNF had deleterious effects on both the striatal TH‐positive fibre density and on drug‐induced rotation tests. Intraventricular injection had no effect. We conclude that preservation of normal motor functions in the intrastriatal 6‐OHDA lesion model requires protection of striatal terminal innervation, and that this can be achieved by intrastriatal, but not nigral or intraventricular, administration of GDNF.
Low‐threshold heat response antagonized by capsazepine in chick sensory neurons, which are capsaicin‐insensitive
Authors: Marín‐Burgin Antonia , Reppenhagen Stephan , Klusch Andreas , Wendland Jens R. , Petersen Marlen 
Published: March 2003

AbstractThe heat‐transducing receptor VR1 cloned from rat sensory neurons can be activated by both noxious heat and capsaicin. As the response of sensory neurons to capsaicin is species dependent, it is conceivable that the responses to noxious heat and to capsaicin are transduced by distinct receptors across different species. Therefore, we investigated responses to noxious heat from a capsaicin‐insensitive (chick) and a capsaicin‐sensitive (rat) species. In chick, whole‐cell patch‐clamp experiments in isolated dorsal root ganglion neurons revealed two populations of neurons with different thresholds to noxious heat, activated at ≈ 43 °C and ≈ 53 °C. In cobalt uptake experiments, the proportion of neurons showing a heat‐induced response increased with increasing heat stimuli. Application of capsaicin (1–10 μm) did not result in inward currents or cobalt uptake. Rat neurons yielded comparable results in heat experiments, but were capsaicin‐sensitive. Although chick neurons are insensitive to capsaicin, the competitive capsaicin antagonist capsazepine (1–10 μm) was effective in blocking heat‐induced responses, verified by patch‐clamp and cobalt uptake methods. The noncompetitive capsaicin antagonist ruthenium red (10 μm) reduced to almost nil the proportion of heat‐responsive neurons identified with the cobalt uptake method. These findings suggest that chick DRG neurons express a low‐threshold heat‐transducing receptor with a pharmacological profile distinct from the low‐threshold heat receptor VR1 cloned from rat DRG neurons. The data support the idea that there might be heat receptor subtypes with differences in the capsaicin binding site.
The Calliphora rpa mutant lacks the PDZ domain‐assembled INAD signalling complex
Authors: Huber Armin , Belusic Gregor , Da Silva Noel , Bähner Monika , Gerdon Gabriele , Draslar Kazimir , Paulsen Reinhard 
Published: March 2003

AbstractThe visual transduction cascade of fly photoreceptors is a G protein‐coupled phospholipase C‐signalling pathway which is assembled into a supramolecular signalling complex by the PDZ (postsynaptic density protein‐95, discs large, Z0–1) domain protein INAD (inactivation no afterpotential D). The norpA‐encoded phospholipase Cβ, the light‐activated transient receptor potential (TRP) Ca2+ channel and an eye‐specific protein kinase C are bound to INAD and together form the core of the signalling complex. In the present study we show that the Calliphora rpa mutant, which has previously been hypothesized to represent an equivalent of Drosophila norpA mutants, has normal amounts of norpA mRNA but fails to express inaD mRNA. Electrophysiological recordings from the eyes of the rpa mutant reveal that the electroretinogram is reduced (about 12% of wild type) but not completely absent, and that it exhibits markedly prolonged deactivation kinetics. Furthermore, rpa mutants display a slow, light‐dependent degeneration of the photoreceptor cells. With respect to the INAD signalling complex, the rpa mutant is similar to the Drosophila inaD null mutant: not only INAD itself, but also the other core components of the INAD signalling complex, are reduced or absent in photoreceptor membranes of rpa flies. Residual TRP is localized throughout the plasma membrane of the photoreceptor cell, rather than being restricted to the microvillar photoreceptor membrane. [35S]methionine‐labelling of newly synthesized retinal proteins reveals that TRP is synthesized in the rpa mutant at wild‐type level, but is transported to or incorporated into the microvillar photoreceptor membrane at a much lower rate. We thus suggest, that the formation of the INAD signalling complex is required for specifically targeting its components to the photoreceptor membrane.
AMPA/kainate receptor‐triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction
Authors: Sensi Stefano L. , Yin Hong Z. , Weiss John H. 
Published: March 2003

AbstractRapid Zn2+ influx through Ca2+‐permeable AMPA/kainate (Ca‐A/K) channels triggers reactive oxygen species (ROS) generation and is potently neurotoxic. The first aim of this study was to determine whether these effects might result from direct mitochondrial Zn2+ uptake. Adapting the mitochondrially sequestered divalent cation sensitive probe, rhod‐2, to visualize mitochondrial Zn2+, present studies indicate that Zn2+ is taken up into these organelles. The specificity of the signal for Zn2+ was indicated by its reversal by Zn2+ chelation, and its mitochondrial origin indicated by its speckled extranuclear appearance and by its elimination upon pretreatment with the mitochondrial protonophore, carbonyl cyanide p‐(trifluoromethoxy)phenylhydrazone (FCCP). Consistent with inhibition of mitochondrial Zn2+ uptake, FCCP also slowed the recovery of cytosolic Zn2+ elevations in Ca‐A/K(+) neurons. Further studies sought clues to the high toxic potency of intracellular Zn2+. In experiments using the mitochondrial membrane polarization (ΔΨm)‐sensitive probe tetramethylrhodamine ethyl ester and the ROS‐sensitive probe hydroethidine, brief kainate exposures in the presence of 300 μm Zn2+ (with or without Ca2+) resulted in prolonged loss of ΔΨm and corresponding prolonged ROS generation in Ca‐A/K(+) neurons, in comparison to the more rapid recovery from loss of ΔΨm and transient ROS generation after kainate/1.8 mm Ca2+ exposures.
The spatial organization of cholinergic mosaics in the adult mouse retina
Authors: Galli‐Resta Lucia , Novelli Elena , Volpini Maila , Strettoi Enrica 
Published: March 2003

AbstractWe analysed the spatial organization of the cholinergic amacrine cell mosaics in the mouse retina, as part of a general study of the major mouse retinal arrays, aiming at providing intrinsic cellular reference grids to monitor anomalies in retinal growth and/or functional organization in mouse models of retinal degeneration. The spatial organization of the cells was analysed by means of the nearest neighbour distance analysis, as well as by the analysis of Voronoi and Delaunay tesselations. We found non random cell spacing in both cholinergic arrays, although the mosaic in the ganglion cell layer tiles the retina scarcely better than a random distribution. Autocorrelation analysis revealed no detectable pattern in cell positioning, but there was a tendency towards a minimal spacing between array elements. Finally, we found no correlation in the spatial organization of the two arrays.
Auditory fear conditioning increases CS‐elicited spike firing in lateral amygdala neurons even after extensive overtraining
Authors: Maren Stephen 
Published: March 2003

AbstractWe examined the influence of extensive overtraining (75 trials) of auditory fear conditioning on the expression of conditional stimulus (CS)‐elicited spike firing in lateral amygdala (LA) neurons. Single units were recorded from chronic multichannel electrodes implanted in the LA of conscious and freely moving rats. In sequential training sessions, the rats received either five or 70 fear conditioning trials, which consisted of a white‐noise CS and a coterminating footshock unconditional stimulus (US). Unpaired (sensitization) controls received the same number of trials, but the CS and US were explicitly unpaired. Paired CS–US presentations yielded robust increases in CS‐elicited spike firing in LA neurons after both five and 70 conditioning trials, and the magnitude of the spike firing increases was correlated with the expression of conditional freezing to the CS. After 75 training trials, maximal conditioning‐related increases in LA firing were exhibited within 20 ms of CS onset, indicating that this increase is mediated by direct thalamo‐amygdala projections. There was no significant increase in CS‐elicited spike firing or freezing behaviour in the unpaired group. These results complement amygdala lesion studies [e.g. Maren, S. (1999a) J. Neurosci., 19, 8696–8703] and support the view that the basolateral complex of the amygdala is involved in the encoding and storage of fear memories even after extensive overtraining.
α‐Latrotoxin forms calcium‐permeable membrane pores via interactions with latrophilin or neurexin
Authors: Van Renterghem Catherine , Iborra Cécile , Martin‐Moutot Nicole , Lelianova Vera , Ushkaryov Yuri , Seagar Michael 
Published: March 2003

AbstractIn order to explore the mechanisms by which α‐latrotoxin activates neurotransmitter release, we have characterized its effects by patch‐clamp methods on cells heterologously expressing its receptors, latrophilin‐1 or neurexin‐Iα. Application of α‐latrotoxin (1 n m) to cells expressing rat latrophilin or neurexin, but not mock‐transfected cells, induced a cationic conductance. In cells expressing latrophilin, current development was slow in the absence of divalent cations, but was accelerated by Ca2+ or Mg2+. In cells expressing neurexin, α‐latrotoxin did not elicit currents in the absence of Ca2+. The toxin‐induced conductance was rectifying, persistent, permeable to monovalent and divalent cations, but blocked by La3+. Single‐channel recording revealed a permanently open state, with the same unitary conductance irrespective of whether cells expressed latrophilin or neurexin. Therefore, while pore formation displayed differences consistent with the reported properties of α‐latrotoxin binding to latrophilin and neurexin, the pores induced by α‐latrotoxin had identical properties. These results suggest that after anchoring to either of its nerve terminal receptors, α‐latrotoxin inserts into the membrane and constitutes a single type of transmembrane ion pore.
Distribution of spinocerebellar Purkinje cell responses to passive forelimb movements in the rat
Authors: Bosco Gianfranco , Giaquinta Genoveffa , Valle Maria Stella , Caserta Cinzia , Casabona Antonino , Perciavalle Vincenzo 
Published: March 2003

AbstractWe recorded Purkinje cell activity throughout the spinocerebellum of anaesthetized rats while imposing circular passive movements to the unrestrained forelimb. The aim was to understand the type of processing of sensory information occurring at the level of the cerebellar cortex, on the basis that precerebellar sensory neurons have been shown to represent whole limb movement parameters better than single joint movements. We observed that neurons representing sensory aspects of arm movements were scattered throughout the spinocerebellar cortex without a distinct segregation from those that did not respond, albeit the relative density of responsive and unresponsive neurons was quite variable and depended on the area of the cortex. Furthermore, Purkinje cells that responded significantly to the arm movement cycles all showed the same response pattern consisting of a firing rate increase during the downward extension of the arm. These results are discussed as suggesting a coordinate framework for the representation of proprioceptive information in the cerebellum congruent to that observed for encoding motor parameters.
Coupled intra‐ and extracellular Ca2+ dynamics in recurrent seizure‐like events
Authors: Szilágyi Nóra , Kovács Richárd , Kardos Julianna 
Published: March 2003

AbstractWe considered the evolution of Ca2+ oscillation dynamics in recurrent seizure‐like events. Dynamic system behaviour was characterized in the state space reconstructed from intra‐ and extracellular [Ca2+] fluctuations simultaneously measured in cultured rat hippocampal slices under low‐[Mg2+] conditions. When associated in the seizure‐like event, these fluctuations occurred on a restricted set, the attractor, embedded in the full state space with less than five degrees of freedom. Instantaneous relative phase differences indicated field potential‐driven phase jumps locked onto seizure‐like events. To account for recurrent dynamics, calculations were performed on different extensions of a model for Ca2+ oscillation. These identified bidirectional, asymmetrical coupling of extracellular with intracellular (cytosolic, Ca2+ store, mitochondrial) Ca2+ dynamics as critical in its development.
Novel mode of nitric oxide neurotransmission mediated via S‐nitroso‐cysteinyl‐glycine
Authors: Salt T. E. , Zhang H. , Mayer B. , Benz B. , Binns K. E. , Do K. Q. 
Published: March 2003

AbstractS‐nitroso‐cysteinyl‐glycine, a novel nitric oxide‐adduct thiol compound, can be detected in the brain (2.3 ± 0.6 pmol/mg protein), and released following stimulation of sensory afferents to the rat ventrobasal thalamus in vivo (resting conditions 17 n m; stimulation: 186 nm). Iontophoretic application of CysNOGly (20–80 nA) onto thalamic neurons in vivo resulted in enhancements of excitatory responses to either NMDA or AMPA (182 ± 13.6% and 244 ± 27.8% of control values, n = 15). CysNOGly enhanced responses to stimulation of vibrissal afferents to 132 ± 2.2% (n = 7) of control values. In contrast, the dipeptide CysGly reduced responses of ventrobasal neurons to NMDA and AMPA (54 ± 8.4% and 55 ± 10.8% of control, n = 5). CysNOGly was also a potent activator of soluble guanylate cyclase in vitro. Moreover, we found that NMDA elevated CysNOGly levels in vitro and this stimulatory effect was reduced by inhibitors of the neuronal NO synthase and of the γ‐glutamyl transpeptidase, suggesting that production of NO and CysGly is a prelude to CysNOGly synthesis. These findings suggest that the nitrosothiol CysNOGly plays a role in synaptic transmission in the ventrobasal thalamus. We propose a novel synaptic buffering mechanism where S‐nitroso‐cysteinyl‐glycine serves to restrict the locus of action of nitric oxide and so increase its local availability for target delivery. This could lead to a change in neuronal responses favouring sensory transmission similar to that seen in wakefulness or arousal in order to locally enhance transmission of persistent sensory stimuli.
A novel brain receptor is expressed in a distinct population of olfactory sensory neurons
Authors: Conzelmann Sidonie , Levai Olga , Bode Barbara , Eisel Ulrich , Raming Klaus , Breer Heinz , Strotmann Jörg 
Published: March 2003

AbstractThree novel G‐protein‐coupled receptor genes related to the previously described RA1c gene have been isolated from the mouse genome. Expression of these genes has been detected in distinct areas of the brain and also in the olfactory epithelium of the nose. Developmental studies revealed a differential onset of expression: in the brain at embryonic stage 17, in the olfactory system at stage E12. In order to determine which cell type in the olfactory epithelium expresses this unique receptor type, a transgenic approach was employed which allowed a coexpression of histological markers together with the receptor and thus visualization of the appropriate cell population. It was found that the receptor‐expressing cells were located very close to the basal membrane of the epithelium; however, the cells extended a dendritic process to the epithelial surface and their axons projected into the main olfactory bulb where they converged onto two or three glomeruli in the dorsal and posterior region of the bulb. Thus, these data provide evidence that this unique type of receptor is expressed in mature olfactory neurons and suggests that it may be involved in the detection of special odour molecules.
Cocaine, but not morphine, induces conditioned place preference and sensitization to locomotor responses in CB1 knockout mice
Authors: Martin Miquel , Ledent Catherine , Parmentier Marc , Maldonado Rafael , Valverde Olga 
Published: March 2003

AbstractThe involvement of cannabinoid CB1 receptors in morphine and cocaine motivational effects was investigated using CB1 knockout mice. For this purpose, we evaluated the rewarding effects in the place conditioning paradigm and the sensitization to the locomotor responses induced by these drugs. The hyperlocomotion induced by acute morphine administration (15 mg/kg, s.c.) was preserved, but the sensitization to this locomotor response induced by chronic morphine treatment was abolished in CB1 mutant mice. Morphine (5 mg/kg, s.c.) induced conditioned place preference in wild‐type mice but failed to produce any response in knockout mice, indicating the inability of morphine to induce rewarding effects in the absence of CB1 cannabinoid receptors. When the aversive effects of morphine withdrawal were investigated using the place aversion paradigm, no differences between genotypes were observed. Acute cocaine (10 mg/kg, i.p.) induced hyperlocomotor responses in wild‐type and knockout mice and a chronic cocaine treatment produced a similar sensitization to this response in both genotypes. In the conditioning place preference paradigm, cocaine (20 mg/kg, i.p.) produced rewarding responses in both wild‐type and knockout mice. These results demonstrate that CB1 receptors are essential for adaptive responses produced by chronic morphine but not by chronic cocaine treatment.
Electrophysiological and behavioural evidence for an antagonistic modulatory role of adenosine A2A receptors in dopamine D2 receptor regulation in the rat dopamine‐denervated striatum
Authors: Strömberg Ingrid , Popoli Patrizia , Müller Christa E. , Ferré Sergi , Fuxe Kjell 
Published: March 2003

AbstractIt has been shown that striatal adenosine A2A receptors can antagonistically interact with dopamine D2 receptors at the membrane level leading to a decrease in the affinity and efficacy of D2 receptors. Extracellular recordings and rotational behaviour were employed to obtain a correlate to these findings in an animal model of Parkinson's disease (PD). The recordings were performed in rats with unilateral 6‐hydroxydopamine (6‐OHDA)‐induced catecholamine depletion. While recording in the dopamine‐depleted striatum, local applications of the dopamine D2 agonist quinpirole reduced neuronal activity. However, when the adenosine A2A antagonist MSX‐3 was applied simultaneously with quinpirole, the inhibition of neuronal firing seen after quinpirole alone was significantly potentiated (P < 0.001, n = 11). In contrast, local application of CGS 21680 attenuated the effect of quinpirole. The doses of MSX‐3 and CGS 21680 used to achieve the modulation of quinpirole action had no effect per se on striatal neuronal firing. Furthermore, rotational behaviour revealed that MSX‐3 dose‐dependently increased the number of turns when administrated together with a threshold dose of quinpirole while no enhancement was achieved when MSX‐3 was combined with SKF 38393. MSX‐3 alone did not induce rotational behaviour. In conclusion, this study shows that low ineffective doses of MSX‐3 enhance the effect of quinpirole on striatal firing rate, while the A2A agonist exerts the opposite action. This mechanism gives a therapeutic potential to A2A antagonists in the treatment of PD by enhancing D2 receptor function.
Subcellular localization of m2 muscarinic receptors in GABAergic interneurons of the olfactory bulb
Authors: Crespo Carlos , Blasco‐Ibáñez José Miguel , Briñón Jesús G. , Alonso José Ramón , Domínguez María Isabel , Martínez‐Guijarro Francisco José 
Published: March 2003

AbstractWe analysed the ultrastructural distribution of the m2 muscarinic receptor (m2R) in the rat olfactory bulb (OB) using immunohistochemical techniques and light and electron microscopy. m2R was differentially distributed within the cellular compartments of γ‐aminobutyric acid (GABA)ergic bulbar interneurons. It is located in the gemmules of granule cells and in the synaptic loci of the interneurons of the external plexiform layer, suggesting that m2R activation could modulate the release of GABA from these interneurons onto principal cells by a presynaptic mechanism. By contrast, the receptor appears in the somata and dendritic trunks of second‐order short‐axon interneurons located in the inframitral layers, suggesting that postsynaptic muscarinic activation in these cells could elicit the inhibition of granule cells, leading to a disinhibition of principal cells. We also detail the anatomical substrate for a new putative muscarinic modulation that has not been previously described, and that could influence the reception of sensory information within the olfactory glomeruli. m2R appears in a subset of GABAergic/dopaminergic juxtaglomerular cells innervated by olfactory axons but is absent in juxtaglomerular cells that do not receive sensory inputs. This finding suggests that m2R activation could modify, through dopaminergic local circuits, the strength of olfactory nerve inputs onto principal cells. Activation of the muscarinic receptor may modulate the olfactory information encoding within olfactory glomeruli and may facilitate the bulbar transmission to superior centres influencing the GABA release by presynaptic and postsynaptic mechanisms. Taken together, our data provide the neuroanatomical basis for a complex action of m2R at different levels in the mammalian OB.