bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct localization of GABAB receptors relative to synaptic sites in the rat cerebellum and ventrobasal thalamus
Authors: Kulik Ákos , Nakadate Kazuhiko , Nyíri Gábor , Notomi Takuya , Malitschek Barbara , Bettler Bernhard , Shigemoto Ryuichi 
Published: March 2003

AbstractMetabotropic γ‐aminobutyric acid receptors (GABABRs) are involved in modulation of synaptic transmission and activity of cerebellar and thalamic neurons. We used subtype‐specific antibodies in pre‐ and postembedding immunohistochemistry combined with three‐dimensional reconstruction of labelled profiles and quantification of immunoparticles to reveal the subcellular distribution of pre‐ and postsynaptic GABABR1a/b and GABABR2 in the rat cerebellum and ventrobasal thalamus. GABABR1a/b and R2 were extensively colocalized in most brain regions including the cerebellum and thalamus. In the cerebellum, immunoreactivity for both subtypes was prevalent in the molecular layer. The most intense immunoreactivity was found in Purkinje cell spines with a high density of immunoparticles at extrasynaptic sites peaking at around 240 nm from glutamatergic synapses between spines and parallel fibre varicosities. This is in contrast to dendrites at sites around GABAergic synapses where sparse and random distribution was found for both subtypes. In addition, more than one‐tenth of the synaptic membrane specialization of spine–parallel fibre synapses were labelled at pre‐ or postsynaptic sites. Weak immunolabelling for both subtypes was also seen in parallel fibres but only rarely in GABAergic axons. In the ventrobasal thalamus, immunolabelling for both receptor subtypes was intense over the dendritic field of thalamocortical cells. Electron microscopy demonstrated an extrasynaptic localization of GABABR1a/b and R2 exclusively in postsynaptic elements. Quantitative analysis further revealed the density of GABABR1a/b around GABAergic synapses was higher than glutamatergic synapses on thalamocortical cell dendrites. The distinct localization of GABABRs relative to synaptic sites in the cerebellum and ventrobasal thalamus suggests that GABABRs differentially regulate activity of different neuronal populations.
Brain catecholamine metabolism in catechol‐O‐methyltransferase (COMT)‐deficient mice
Authors: Huotari Marko , Gogos Joseph A. , Karayiorgou Maria , Koponen Olli , Forsberg Markus , Raasmaja Atso , Hyttinen Juha , Männistö Pekka T. 
Published: March 2003

AbstractCatechol‐O‐methyltransferase (COMT) catalyses theO‐methylation of compounds having a catechol structure and its main function involves the elimination of biologically active or toxic catechols and their metabolites. By means of homologous recombination in embryonic stem cells, a strain of mice has been produced in which the gene encoding the COMT enzyme is disrupted. We report here the levels of catecholamines and their metabolites in striatal extracellular fluid in these mice as well as in homogenates from different parts of the brain, under normal conditions and after acute levodopa administration. In immunoblotting studies, COMT‐knockout mice had no COMT protein in brain or kidney tissues but the amounts of catecholamine synthesizing and other metabolizing enzyme proteins were normal. Under normal conditions, COMT deficiency does not appear to affect significantly brain dopamine and noradrenaline levels in spite of relevant changes in their metabolites. This finding is consistent with previous pharmacological studies with COMT inhibitors and confirms the pivotal role of synaptic reuptake processes and monoamine oxidase‐dependent metabolism in terminating the actions of catecholamines at nerve terminals. In contrast, when COMT‐deficient mice are challenged withl‐dihydroxyphenylalanine, they show an extensive accumulation of 3,4‐dihydroxyphenylacetic acid and dihydroxyphenylglycol and even dopamine, revealing an important role for COMT under such situations. Notably, in some cases these changes appear to beComtgene dosage‐dependent, brain‐region specific and sexually dimorphic. Our results may have implications for improving the treatment of Parkinson's disease and for understanding the contribution of the natural variation in COMT activity to psychiatric phenotypes.
Magnetic oscillatory responses to lateralization changes of natural and artificial sounds in humans
Authors: Kaiser Jochen , Birbaumer Niels , Lutzenberger Werner 
Published: March 2003

AbstractOscillatory signals in human magnetoencephalogram were investigated as correlates of cortical network activity in response to sound lateralization changes. Previously, we found lateralized presentations of a monosyllabic word to elicit posterior temporo‐parietal gamma‐band activity, possibly reflecting synchronization of neuronal assemblies in putative auditory dorsal stream areas. In addition, beta activity was decreased over sensorimotor regions, suggesting the activation of motor networks involved in orientating. The present study investigated responses to lateralization changes of both a barking dog sound and a distorted noise to test whether beta desynchronization would depend on the sound's relevance for orientating. Eighteen adults listened passively to 900 samples of each sound in separate location mismatch paradigms with midline standards and both right‐ and left‐lateralized deviants. Lateralized distorted noises were accompanied by enhanced spectral amplitude at 58–73 Hz over right temporo‐parietal cortex. Left‐lateralized barking dog sounds elicited right and right‐lateralized sounds elicited bilateral temporo‐parietal spectral amplitude increases at ≈ 77 Hz. This replicated the involvement of posterior temporo‐parietal areas in auditory spatial processing. Only barking dog sounds, but not distorted noises, gave rise to 30 Hz desynchronization over contralateral sensorimotor areas, parieto‐frontal gamma coherence increases and beta coherence reductions between sensorimotor and prefrontal sensors. Apparently passive listening to lateralized natural sounds with a potential biological relevance led to an activation of motor networks involved in the automatic preparation for orientating. Parieto‐frontal coherence increases may reflect enhanced coupling of networks involved in the integration of auditory spatial and motor processes.
Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan
Authors: Romanczyk T. B. , Weickert C. Shannon , Webster M. J. , Herman M. M. , Akil M. , Kleinman J. E. 
Published: March 2003

AbstractSignalling through tyrosine kinase receptor B (trkB) influences neuronal survival, differentiation and synaptogenesis. trkB exists in a full‐length form (trkBTK+), which contains a catalytic tyrosine kinase (TK) domain, and a truncated form (trkBTK–), which lacks this domain. In the rodent brain, expression of trkBTK+ decreases and trkBTK– increases during postnatal life. We hypothesized that both forms of trkB receptor mRNA would be present in the human neocortex and that the developmental profile of trkB gene expression in human may be distinct from that in rodent. We detected both trkBTK+ and trkBTK– mRNA in RNA extracted from multiple human brain regions by Northern blot. Using in situ hybridization, we found trkBTK+ mRNA in all cortical layers, with highest expression in layer IV and intermediate‐to‐high expression in layers III and V of the human dorsolateral prefrontal cortex. trkBTK+ mRNA was present in neurons with both pyramidal and nonpyramidal shapes in the dorsolateral prefrontal cortex. trkBTK+ mRNA levels were significantly increased in layer III in young adults as compared with infants and the elderly. In the elderly, trkBTK+ mRNA levels were reduced markedly in all cortical layers. Unlike the mRNA encoding the full‐length form of trkB, trkBTK– mRNA was distributed homogeneously across the grey matter, and trkBTK– mRNA levels increased only slightly during postnatal life. The results suggest that neurons in the human dorsolateral prefrontal cortex are responsive to neurotrophins throughout postnatal life and that this responsiveness may be modulated during the human lifespan.
Orexin receptor‐1 (OX‐R1) immunoreactivity in chemically identified neurons of the hypothalamus: focus on orexin targets involved in control of food and water intake
Authors: Bäckberg Matilda , Hervieu Guillaume , Wilson Shelagh , Meister Björn 
Published: March 2003

AbstractThe neuropeptides orexin‐A and orexin‐B are produced in neurons of the lateral hypothalamic area and have been implicated to be involved in the regulation of food/water intake and sleep–wake control. The orexins act at two different G‐protein‐coupled orexin receptors (OX‐R1 and OX‐R2) that are derived from separate genes and expressed differentially throughout the central nervous system. In the present study, we have used a polyclonal antipeptide antiserum to analyse in detail the distribution of OX‐R1‐immunoreactive neurons in the rat hypothalamus. In order to identify the chemical mediators of orexin action in the hypothalamus, the OX‐R1‐containing neurons were characterized with regard to the content of peptides shown previously to affect ingestive and drinking behaviour. Neurons containing OX‐R1 immunoreactivity were widely distributed in the hypothalamus with cell bodies located in the suprachiasmatic, periventricular, paraventricular (both magno‐ and parvocellular division), supraoptic, arcuate, ventromedial, dorsomedial and tuberomammillary nuclei and the lateral hypothalamic area. In magnocellular neurons of the paraventricular and supraoptic nuclei, OX‐R1 immunoreactivity was seen in both vasopressin‐ and oxytocin‐containing neurons. OX‐R1 immunoreactivity was demonstrated in vasopressin and vasoactive intestinal polypeptide (VIP) neurons of the suprachiasmatic nucleus, in somatostatin neurons of the periventricular nucleus and in corticotropin‐releasing hormone (CRH) neurons of the parvocellular paraventricular nucleus. In the arcuate nucleus, OX‐R1 immunoreactivity was present in neuropeptide Y (NPY) and agouti‐related peptide (AGRP) neurons of the ventromedial part as well as in proopiomelanocortin (POMC) and cocaine‐ and amphetamine‐regulated transcript (CART) neurons of the ventrolateral division. In the lateral hypothalamic area, OX‐R1 immunoreactivity was demonstrated in melanin‐concentrating hormone (MCH)‐ and orexin‐containing neurons. In the hypothalamic tuberomammillary nucleus, OX‐R1‐immunoreactivity was shown in many histamine‐containing neurons. The results support the idea that orexins have important actions on hypothalamic neurons that control food intake and fluid balance, but also that orexins may regulate other neuroendocrine systems.
Mu and kappa opioid agonists modulate ventral tegmental area input to the ventral pallidum
Authors: Mitrovic Igor , Napier T. Celeste 
Published: March 2003

AbstractThe ventral pallidum (VP) is situated at the convergence of midbrain dopamine and accumbal opioid efferent projections. Using in vivo electrophysiological procedures in chloral hydrate‐anaesthetized rats, we examined whether discrete application of µ‐ [D‐Ala2,N‐Me‐Phe4,Gly‐ol5 (DAMGO)] or κ− (U50488) opioid receptor agonists could alter VP responses to electrical stimulation of ventral tegmental area. Rate suppressions occurred frequently following ventral tegmental area stimulation. Consistent with an involvement of dopamine in this effect, none of the 12 spontaneously active ventral pallidal neurons recorded in rats that had monoamines depleted by reserpine responded to electrical stimulation of ventral tegmental area. Moreover, in intact rats, the dopamine antagonist flupenthixol attenuated evoked suppression in 100% of the neurons tested; however, the GABAA antagonist bicuculline was able to slightly attenuate the response in 50% of the neurons tested. These observations concur with our previous studies in indicating that ventral tegmental area stimulation releases dopamine (and sometimes GABA) onto ventral pallidal neurons. Both DAMGO and U50488 decreased the inhibitory effects of ventral tegmental area stimulation. These effects on the endogenously released transmitter differed from those seen with exogenously applied dopamine, for DAMGO did not alter the efficacy or potency of microiontophoretically applied dopamine. Taken together, these observations suggest that the interaction between DAMGO and dopamine does not occur at a site that is immediately postsynaptic to the dopaminergic input within the VP, but rather that opioid modulation involves mechanisms governing presynaptically released dopamine. These modulatory processes would enable ventral pallidal opioids to gate the influence of ventral tegmental area dopamine transmission on limbic system outputs at the level of the VP.
Knocking out the glial glutamate transporter GLT‐1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia
Authors: Hamann Martine , Rossi David J. , Marie Hélène , Attwell David 
Published: March 2003

AbstractGlutamate release in ischaemia triggers neuronal death. The major glial glutamate transporter, GLT‐1, might protect against glutamate‐evoked death by removing extracellular glutamate, or contribute to death by reversing and releasing glutamate. Previous studies of the role of GLT‐1 in ischaemia have often used the GLT‐1 blocker dihydrokainate at concentrations that affect transporters other than GLT‐1 and which affect kainate, N‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors. In hippocampal slices from postnatal day 14 mice lacking GLT‐1, the current response of area CA1 pyramidal cells to superfused AMPA and NMDA (which are not taken up) was unaffected, whereas the response to 100 µm glutamate was more than doubled relative to that in wild‐type littermates, a finding consistent with a decrease in glutamate uptake. In response to a few minutes of simulated ischaemia, pyramidal cells in wild‐type mice showed a large and sudden inward glutamate‐evoked current [the anoxic depolarization (AD) current], which declined to a less inward plateau. In mice lacking GLT‐1, the time to the occurrence of the AD current, its amplitude, the size of the subsequent plateau current and the block of the plateau current by glutamate receptor blockers were all indistinguishable from those in wild‐type mice. We conclude that GLT‐1 does not contribute significantly to glutamate release or glutamate removal from the extracellular space in early simulated ischaemia. These data are consistent with glutamate release being by reversal of neuronal transporters, and with uptake into glia being compromised by the ischaemia‐evoked fall in the level of ATP needed to convert glutamate into glutamine.
A peripheral nervous system actin‐binding protein regulates neurite outgrowth
Authors: Ravenall Samantha J. , Gavazzi Isabella , Wood John N. , Akopian Armen N. 
Published: March 2003

AbstractDifference cloning has identified a Villin‐like mRNA transcript expressed selectively in peripheral sensory and sympathetic neurons. Pervin, the encoded 820‐amino acid protein, has 60% identity with Villin and is the rat homologue of Advillin. Coimmunoprecipitation studies demonstrate that Pervin and actin interact in vivo. Transfection of COS‐7 epithelial cell lines demonstrates colocalization of epitope‐tagged Pervin with green fluorescent protein‐actin and results in an increase in process formation. This effect is abolished when the putative actin‐bundling headpiece of Pervin is deleted. Biolistic transfection of primary cultures of rat dorsal root ganglion sensory neurons also results in increased neurite outgrowth with FLAG‐tagged Pervin. Deletion of the actin‐bundling headpiece inhibits normal neurite growth. These data suggest that Pervin may play a significant role in regulating process outgrowth in peripheral neurons through a mechanism that involves the activity of an actin‐bundling domain.
Modulation by 5‐hydroxytryptamine of nicotinic acetylcholine responses recorded from an identified cockroach (Periplaneta americana) motoneuron
Authors: Butt Simon J. B. , Pitman Robert M. 
Published: March 2003

AbstractRecordings from the soma of the cockroach (Periplaneta americana) fast coxal depressor motoneuron (Df) were made while acetylcholine (ACh) was regularly pressure‐applied locally from a micropipette. The modulatory effects upon these nicotinic ACh responses of bath‐applied 5‐hydroxytryptamine (5‐HT, serotonin), dopamine and octopamine were investigated under either current‐clamp or voltage‐clamp conditions. The biogenic amines reversibly suppressed, but never totally abolished, ACh responses, 5‐HT being the most potent, with a threshold near 10−6 m (EC50 = 5 × 10−5 m). Occlusion experiments indicate that the amines share a common mechanism at the level of either receptors or second messenger pathways. The amines also modulated responses to nicotine or carbachol (each of which resists hydrolysis by acetylcholinesterases), indicating that the amines did not act by accelerating ACh degradation. Pharmacological antagonists were used in an attempt to characterize the receptor responsible for amine‐mediated modulation. Although a number of antagonists mimicked the action of amines rather than producing blockade, the antagonistic actions of LSD and RS23597 pointed strongly to a receptor‐mediated mechanism, but did not allow receptor identification. The magnitude of the modulatory effect of 5‐HT was significantly reduced by intracellular guanosine‐5′‐O‐(2‐thiodiphosphate) (GDP‐β‐S), indicating involvement of a G‐protein. Intracellular injection of the calcium chelator BAPTA did not block the modulatory effect of 5‐HT, showing that the amines do not operate through the calcium‐dependent pathway by which muscarinic receptors act on nicotinic currents. The adenylate cyclase inhibitor dideoxyadenosine (DDA), on the other hand, did attenuate the action of 5‐HT, suggesting involvement of cyclic AMP.
Insulin‐like growth factor‐II/Mannose‐6‐phosphate receptor in the spinal cord and dorsal root ganglia of the adult rat
Authors: Hawkes C. , Kar S. 
Published: March 2003

AbstractThe insulin‐like growth factor‐II/mannose‐6‐phosphate (IGF‐II/M6P) receptor is a multifunctional transmembrane glycoprotein, which interacts with a number of molecules, including IGF‐II and M6P‐containing lysosomal enzymes. The receptor is widely distributed throughout the brain and is known to be involved in lysosomal enzyme trafficking, cell growth, internalization and degradation of IGF‐II. In the present study, using autoradiographic, Western blotting and immunocytochemical methods, we provide the first report that IGF‐II/M6P receptors are discretely distributed at all major segmental levels of the spinal cord and dorsal root ganglia of the adult rat. In the spinal cord, a high density of [125I]IGF‐II binding sites was evident in the ventral horn (lamina IX) and in areas around the central canal (lamina X), whereas intermediate grey matter and dorsal horn were associated with moderate receptor levels. The dorsal root ganglia exhibited rather high density of [125I]IGF‐II binding sites. Interestingly, meninges present around the spinal cord displayed highest density of [125I]IGF‐II binding compared to any given region of the spinal grey mater or the dorsal root ganglia. Western blot results indicated the presence of the IGF‐II/M6P receptor at all major levels of spinal cord and dorsal root ganglia, with little segmental variation. At the cellular level, spinal motorneurons demonstrated the most intense IGF‐II/M6P receptor immunoreactivity, followed by interneurons in the intermediate region and deeper dorsal horn. Some scattered IGF‐II/M6P immunoreactive fibers were found in the superficial laminae of the dorsal horn and dorsolateral funiculus. The meninges of the spinal cord also seemed to express IGF‐II receptor immunoreactivity. In the dorsal root ganglia, receptor immunoreactivity was evident primarily in a subset of neurons of all diameters. These results, taken together, provide anatomical evidence of a role for the IGF‐II/M6P receptor in general cellular functions such as transport of lysosomal enzymes and/or internalization followed by clearance of IGF‐II in the spinal cord and dorsal root ganglia.
Alpha‐adrenoreceptor activation modulates swimming via glycinergic and GABAergic inhibitory pathways in Xenopus laevis tadpoles
Authors: Merrywest Simon D. , Fischer Hanno , Sillar Keith T. 
Published: March 2003

AbstractThis study focuses upon the network pathways underlying the adrenoreceptor‐mediated modulation of fictive swimming in the immobilized Xenopus laevis tadpole. As shown recently, noradrenaline (NA) increases cycle periods while simultaneously reducing the rostrocaudal delay in head‐to‐tail firing and the duration of swimming episodes. Furthermore, both swimming frequency and duration are reduced by selective pharmacological activation of α1‐ and/or α2‐adrenoreceptors, while α1‐receptor activation also reduces rostrocaudal delays. We show that NA could still modulate aspects of swimming after blocking either glycine or GABAA receptors with strychnine and bicuculline, respectively. Furthermore, after prior application of NA, strychnine could counteract noradrenergic effects on cycle periods and rostrocaudal delays, while bicuculline could counteract effects on cycle periods, suggesting that these two fast inhibitory pathways are both involved in the NA modulation of swimming. In addition, blocking glycine receptors reduced the effects of α1‐receptors on cycle periods and delays, while blocking GABAA receptors had no effect. Blocking either glycine or GABAA receptors, however, lessened the reduction in swimming frequency by α2‐receptors. In addition, pre‐application of bicuculline prevented a reduction in episode durations by NA, α1‐ and α2‐receptors. Our findings suggest that the noradrenergic modulation of Xenopus swimming is mediated via α‐adrenoreceptors interacting with both glycinergic and GABAergic inhibitory pathways. Both α1‐ and α2‐receptor activation influences the GABAergic pathway controlling the duration of swimming episodes and is involved in the glycinergic modulation of the swimming rhythm and its longitudinal co‐ordination, with α2‐receptors additionally affecting swimming frequency through GABAergic pathways.
Bilateral overactivation of the sensorimotor cortex in the unilateral rodent model of Parkinson's disease – a functional magnetic resonance imaging study
Authors: Pelled Galit , Bergman Hagai , Goelman Gadi 
Published: March 2003

AbstractFunctional magnetic resonance imaging (fMRI) is used to investigate the basal ganglia (BG)–cortex circuit using a rat model of Parkinson's disease (PD). The model involves a unilateral destruction of the right substantia nigra by intranigral injection of the dopaminergic neurotoxin 6‐hydroxydopamine. Volume of cortical activity was measured by the blood oxygenation level‐dependent contrast method while applying electrical forepaw stimulation. The main findings are the following. (i) Contrary to the predictions of the classic model but in line with recent experimental results (positron emission tomography, fMRI and electrophysiology), an increased cortical activity in the sensorimotor cortex of PD rats compared with sham‐operated or normal rats was found. (ii) A diffuse neuronal activity at large cortical areas that were not related directly to the stimulation used, was observed. (iii) No difference was found between the lesion and the nonlesion hemispheres when the left or the right forepaw was stimulated; both cortices show significant overactivation of the sensorimotor cortices in addition to diffuse cortical activation. The last finding could be explained by either corticocortical connections or by bilateral BG–cortex connections. These finding suggest that the mutual influence of the two hemispheres is important in the pathophysiology of the BG–cortex circuit and might be crucial in predicting treatments.