bluuebunny/crossref_metadata_2025 huggingface dataset:
The central acoustic tract and audio‐vocal coupling in the horseshoe bat, Rhinolophus rouxi
Authors: Behrend O. , Schuller G.
Published: March 2003

Doppler shift compensation (DSC) behaviour in horseshoe bats is a remarkable example of sensorimotor feedback that stabilizes the echo frequency at the bat's optimum hearing range regardless of motion‐induced frequency shifts in the echoes. Searching for a related neural interface, the nucleus of the central acoustic tract (NCAT) was investigated in the echolocating horseshoe bat, Rhinolophus rouxi, using various neurophysiological and tracer methods. The NCAT receives bilateral auditory input from the cochlear nuclei and sends projections to regions outside the classical acoustic pathway like the pretectal area or the superior colliculus. The binaural input is excitatory from the contralateral and inhibitory from the ipsilateral ear to 53% of the units, and auditory responses were biased to frontal and contralateral directions. The best frequencies of NCAT neurons match a narrow range above the main frequency component of the bat's species‐specific echolocation call (62% of the units), and the neurons exhibit extremely sharp tuning (Q10dB up to 632). DSC is degraded by unilateral electrical or pharmacological microstimulation of the NCAT, and heavily impaired by unilateral lesion of the region. Altogether, the efferents of the NCAT to prevocal areas, the tuning of its neurons to the DSC‐relevant echo frequency range, and the possibility to affect DSC by manipulation of the NCAT, support the assumption that the nucleus plays an important role in audio‐vocal control in the horseshoe bat.
Cooperative changes in GABA, glutamate and activity levels: the missing link in cortical plasticity
Authors: Arckens Lutgarde , Schweigart Georg , Qu Ying , Wouters Griet , Pow D. V. , Vandesande Frans , Eysel Ulf T. , Orban Guy A.
Published: March 2003

Different intracortical mechanisms have been reported to contribute to the substantial topographic reorganization of the mammalian primary visual cortex in response to matching lesions in the two retinas: an immediate expansion of receptive fields followed by a gradual shift of excitability into the deprived area and finally axonal sprouting of laterally projecting neurons months after the lesion. To gain insight into the molecular mechanisms of this adult plasticity, we used immunocytochemical and bioanalytical methods to measure the glutamate and GABA neurotransmitter levels in the visual cortex of adult cats with binocular central retinal lesions. Two to four weeks after the lesions, glutamate immunoreactivity was decreased in sensory‐deprived cortex as confirmed by HPLC analysis of the glutamate concentration. Within three months normal glutamate immunoreactivity was restored. In addition, the edge of the unresponsive cortex was characterized by markedly increased glutamate immunoreactivity 2–12 weeks postlesion. This glutamate immunoreactivity peak moved into the deprived area over time. These glutamate changes corresponded to decreased spontaneous and visually driven activity in unresponsive cortex and to strikingly increased neuronal activity at the border of this cortical zone. Furthermore, the previously reported decrease in glutamic acid decarboxylase immunoreactivity was found to reflect decreased GABA levels in sensory‐deprived cortex. Increased glutamate concentrations and neuronal activity, and decreased GABA concentrations, may be related to changes in synaptic efficiency and could represent a mechanism underlying the retinotopic reorganization that occurs well after the immediate receptive field expansion but long before the late axonal sprouting.
Up‐regulation of growth‐associated protein 43 mRNA in rat medial septum neurons axotomized by fimbria‐fornix transection
Authors: Haas Carola A. , Hollerbach Ewald , Deller Thomas , Naumann Thomas , Frotscher Michael
Published: March 2003

Transection of septohippocampal fibres is widely used to study the response of CNS neurons to axotomy. Septohippocampal projection neurons survive axotomy and selectively up‐regulate the transcription factor c‐Jun. In the present study we investigated whether these cells concomitantly up‐regulate the growth‐associated protein‐43 (GAP‐43), a potential target gene of c‐Jun implicated in axonal growth and regeneration. Using in situ hybridization histochemistry (ISHH) it was demonstrated that postlesional c‐jun mRNA expression is accompanied by an increased expression of GAP‐43 mRNA in the medial septum 3 days following fimbria‐fornix transection (FFT). The increase reached a maximum at 7 days and gradually declined thereafter (17 days, 3 weeks). Retrograde prelabeling with Fluoro‐Gold followed by axotomy and ISHH revealed that GAP‐43 mRNA was up‐regulated in septohippocampal projection neurons. Colocalization of GAP‐43 mRNA and choline acetyltransferase protein showed that GAP‐43 mRNA was expressed by cholinergic medial septal neurons after axotomy. Selective immunolesioning of the cholinergic component of the septohippocampal projection with 192 IgG‐saporin followed by FFT demonstrated that GAP‐43 mRNA was also synthesized by axotomized GABAergic neurons. These results demonstrate an up‐regulation of GAP‐43 mRNA in axotomized septohippocampal projection neurons independent of their transmitter phenotype which is closely correlated with c‐Jun expression. Because the GAP‐43 gene contains an AP‐1 site, we hypothesize a c‐Jun‐driven up‐regulation of GAP‐43 in lesioned medial septal neurons that may contribute to their survival and regenerative potential following axotomy.
Migrating neurons cross a reelin‐rich territory to form an organized tissue out of embryonic cortical slices
Authors: Hedin‐Pereira Cecilia , DeMoraes Elizabeth C. P. , Santiago Marcelo F. , Méndez‐Otero Rosalia , Lent Roberto
Published: March 2003

In this study we show that the radial migration of neuronal precursors out of cerebral cortex of embryonic brain slices cultured for 4–7 days gives rise to an organized tissue that forms de novo off developing slices. In our in vitro preparations, migrating neuronal precursors overshot the marginal zone, as did the elongation of radial glial processes out of the slices. These cells detached from radial glia at a distance from the cortex and differentiated into pyramidal and nonpyramidal profiles that expressed different neuronal markers. Glial precursors were shown to proliferate in the slice and in the neotissue, and to differentiate into astrocytes. We show that cells expressing reelin in the marginal zone of embryonic cortical slices persist after a week in culture, which implies that neuronal migration is not necessarily hindered by the presumed stop signals provided by reelin in the marginal zone. Furthermore, our results provide a new model for in vitro studies of migration and differentiation during cortical development.
Mapping of c‐fos gene expression in the brain during morphine dependence and precipitated withdrawal, and phenotypic identification of the striatal neurons involved
Authors: Georges François , Stinus Luis , Le Moine Catherine
Published: March 2003

The c‐fos gene is expressed in the central nervous system in response to various neuronal stimuli. Using in situ hybridization, we examined the effects of chronic morphine treatment and withdrawal on c‐fos mRNA in the rat brain, and particularly within identified striatal neurons. Morphine dependence was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Placebo animals and morphine‐dependent rats showed a very weak c‐fos mRNA expression in all the structures studied. Our study emphasized the spatial variations in c‐fos mRNA expression, and also revealed a peak expression of c‐fos mRNA at 1 h after naltrexone‐precipitated withdrawal in the projection areas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c‐fos mRNA expression in the two efferent populations of the striatum (i.e. striatonigral and striatopallidal neurons) both in the caudate putamen and nucleus accumbens. Moreover, the proportions of activated neurons during morphine withdrawal are different in the caudate putamen (mostly in striatopallidal neurons) and in the shell and core parts of the nucleus accumbens (mostly in striatonigral neurons). The activation of striatopallidal neurons suggests a predominant dopaminergic regulation on c‐fos gene expression in the striatum during withdrawal. On the contrary, c‐fos induction in striatonigral neurons during withdrawal seems to involve a more complex regulation like opioid–dopamine interactions via the µ opioid receptor and the D1 dopamine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems.
Differential neuronal expression and projections of melanin‐concentrating hormone (MCH) and MCH‐gene‐overprinted‐polypeptide (MGOP) in the rat brain
Authors: Toumaniantz Gilles , Ferreira Patricia C. , Allaeys Isabelle , Bittencourt Jackson C. , Nahon Jean‐Louis
Published: March 2003

The rat melanin‐concentrating hormone (MCH) gene may produce, through alternative splicing, either the precursor of MCH and neuropeptide EI, two neuropeptides coexpressed in the zona incerta (ZI) and lateral hypothalamus (LHA), or a putative protein we named previously MCH‐gene‐overprinted‐polypeptide (MGOP). First, we investigated the distribution and relative expression of MCH and MGOP mRNA in the rat brain by Northern blotting, RT‐PCR and in situ hybridization. MGOP gene transcripts were detected mainly in the hypothalamus only by RT‐PCR. Second, different antisera were raised toward the C‐terminus of MGOP and used to identify the translational products. In the rat brain, no MGOP‐processed peptide could be detected based on RP‐HPLC coupled to specific RIA. A polypeptide of 14 kDa was found in the secretory pathway of transfected monkey COS7 cells expressing recombinant MGOP. In the rat hypothalamus, a specific protein of 12 kDa was identified by Western blot analysis. Finally, distribution of MGOP‐immunoreactivity (IR) was investigated in the rat brain. Colocalization studies demonstrated that 98% of the MGOP‐expressing perikarya in ZI/LHA also synthesized MCH. In addition, numerous, strongly stained MGOP‐containing neurons were encountered in the hypothalamic periventricular nucleus. Perikarya labelled with MGOP antiserum were also found scattered in the cortex, caudate putamen, amygdala and lateral septal nucleus. MCH was not detected in these MGOP‐containing neurons. Strikingly, dense staining of terminals was observed with MGOP antiserum but not with MCH antibodies in the suprachiasmatic, ventromedial and arcuate nuclei, and also in the external layer of the median eminence. These results demonstrated that MGOP and MCH‐IR overlapped in LHA/ZI but displayed a differential distribution in other areas. Based on this cerebral distribution, MGOP may act as a new secreted protein in regulating many neuroendocrine functions, such as nursing, feeding and growth control in associated behavioural components.
Muscarinic and PACAP receptor interactions at pontine level in the rat: significance for REM sleep regulation
Authors: Ahnaou A. , Laporte A. M. , Ballet S. , Escourrou P. , Hamon M. , Adrien J. , Bourgin P.
Published: March 2003

Cholinergic and PACAPergic systems within the oral pontine reticular nucleus (PnO) play a critical role in REM sleep generation in rats. In this present work, we have investigated whether REM sleep enhancement induced by carbachol (a cholinergic agonist) or PACAP, depends on an interaction between muscarinic and PACAP receptors. This hypothesis was tested by recording sleep–wake cycles in freely moving rats injected into the PnO with PACAP in combination with the muscarinic receptor antagonist atropine, or with carbachol in combination with the PACAP receptor antagonist PACAP6‐27. When administered alone, PACAP (3 pmol) or carbachol (110 pmol) induced an enhancement of REM sleep during 8 h (+61%, n = 8; +70%, n = 5), which was totally prevented by infusion of atropine (290 pmol) for PACAP, or of PACAP6‐27 (3 pmol) for carbachol. Quantitative autoradiographic studies indicated that (i) PACAP (10−9−10−7 m) induced in the PnO an increase (+35%) of the specific binding of the muscarinic antagonist [3H]quinuclidinyl benzylate, which could be completely prevented by PACAP6‐27 (IC50 = 8 × 10−8 m) and (ii) both carbachol and PACAP enhanced [35S]GTP‐γ‐S binding in a concentration‐dependent manner in the PnO. The maximal increase due to carbachol was significantly higher in the presence (+126%) than in the absence (+102%) of PACAP (0.1 µm). These data showed that interactions between muscarinic and PACAP receptors do exist within the PnO and play a role in the local mechanisms of REM sleep control in the rat.
Differential induction of NF‐κB activity and neural cell death by antidepressants in vitro
Authors: Post Anke , Crochemore Christophe , Uhr Manfred , Holsboer Florian , Behl Christian
Published: March 2003

Tricyclic antidepressants and selective serotonin reuptake inhibitors are here shown to induce cell death in a neural cell line. The exposure to these drugs led to increased generation of reactive oxygen species and a concomitant reduction of intracellular glutathione levels. Furthermore, these antidepressants induced DNA fragmentation and increased the transcriptional and DNA‐binding activity of NF‐κB. In contrast, treatment with type A and B monoamine oxidase inhibitors did not induce changes in NF‐κB activity and did not exert a detrimental influence on cell viability. These results indicate that some antidepressant drugs may cause both oxidative stress and changes in cellular antioxidative capacity, resulting in altered NF‐κB activity and, ultimately, cell death.
Nerve growth factor expression in parasympathetic neurons: regulation by sympathetic innervation
Authors: Hasan Wohaib , Smith Peter G.
Published: March 2003

Interactions between sympathetic and parasympathetic nerves are important in regulating visceral target function. Sympathetic nerves are closely apposed to, and form functional synapses with, parasympathetic axons in many effector organs. The molecular mechanisms responsible for these structural and functional interactions are unknown. We explored the possibility that Nerve Growth Factor (NGF) synthesis by parasympathetic neurons provides a mechanism by which sympathetic–parasympathetic interactions are established. Parasympathetic pterygopalatine ganglia NGF‐gene expression was examined by in situ hybridization and protein content assessed by immunohistochemistry. Under control conditions, NGF mRNA was present in ≈ 60% and NGF protein was in 40% of pterygopalatine parasympathetic neurons. Peripheral parasympathetic axons identified by vesicular acetylcholine transporter‐immunoreactivity also displayed NGF immunoreactivity. To determine if sympathetic innervation regulates parasympathetic NGF expression, the ipsilateral superior cervical ganglion was excised. Thirty days postsympathectomy, the numbers of NGF mRNA‐positive neurons were decreased to 38% and NGF immunoreactive neurons to 15%. This reduction was due to a loss of sympathetic nerve impulse activity, as similar reductions were achieved when superior cervical ganglia were deprived of preganglionic afferent input for 40 days. These findings provide evidence that normally NGF is synthesized by parasympathetic neurons and transported anterogradely to fibre terminals, where it may be available to sympathetic axons. Parasympathetic NGF expression, in turn, is augmented by impulse activity within (and presumably transmitter release from) sympathetic axons. It is suggested that parasympathetic NGF synthesis and its modulation by sympathetic innervation provides a molecular basis for establishment and maintenance of autonomic axo‐axonal synaptic interactions.
Activation of ionotropic glutamate receptors reduces the production of transforming growth factor‐ß2 by developing neurons
Authors: Dobbertin Alexandre , Gervais Annie , Glowinski Jacques , Mallat Michel
Published: March 2003

Neuronal cultures derived from developing rat cerebral cortex were used to investigate the influence of glutamate receptors on the neuronal production of transforming growth factor‐ß2 (TGFß2), a multifunctional cytokine that modulates neuronal and glial growth. Long‐term exposure (48 h) of cortical neurons to selective antagonists of N‐methyl‐d‐aspartate (NMDA) and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA)/kainate receptors markedly increased TGFß2 levels in the culture medium. Conversely, treatment with NMDA or kainate reduced TGFß2 to levels below those in untreated cultures. The effect of kainate did not require NMDA receptor activity. Neuronal depolarization with K+ also reduced TGFß2 levels by opening voltage‐gated L‐type Ca2+ channels. Semi‐quantitative RT–PCR measurements of neuronal TGFß2 mRNA showed that NMDA or AMPA/kainate receptor stimulation reduced TGFß2 mRNA levels. These results demonstrate that tonic activation of glutamate‐gated cation channels downregulates neuronal expression of the TGFß2 gene and provide evidence for a novel mechanism whereby excitatory amino acids could influence the development of glial and neuronal lineages.
The effect of riluzole treatment in rats on the survival of injured adult and grafted embryonic motoneurons
Authors: Nógrádi Antal , Vrbová Gerta
Published: March 2003

The effect of riluzole on the survival of injured motoneurons was studied. The L4 ventral root was avulsed and reimplanted into the spinal cord. Immediately after the operation, 4 animals were treated with riluzole for 3 weeks while another 4 animals received no treatment after the operation. Three months later the fluorescent dyes, Fast Blue and Diamidino Yellow, were applied to the cut ventral ramus of the L4 spinal nerve, for retrograde labelling of neurons. Three days later, the spinal cords were processed to reveal the retrograde‐labelled cells. In untreated animals, there were 20 ± 2.1 labelled neurons (± SEM), while in animals treated with riluzole there were 723 ± 26. Thus, treatment with riluzole dramatically enhanced the survival of injured motoneurons. In another series of experiments, after avulsion of the L4 ventral root and its reinsertion, embryonic spinal cord pieces were grafted into the host cord. Five animals received riluzole treatment and 4 were left untreated. In the untreated animals, 125 ± 5.1 retrograde‐labelled cells of both graft and host origin were detected. In rats treated with riluzole, 645 ± 35.7 retrograde‐labelled cells were seen and almost all of these were of host origin. Thus, treatment with riluzole enhanced the survival of injured host motoneurons, and by doing so, (i) reduced the ability of grafted neurons to extend their axons into the reimplanted L4 ventral root, and (ii) reduced the survival of the grafted cells.
Enhancement of hippocampal LTP, reference memory and sensorimotor gating in mutant mice lacking a telencephalon‐specific cell adhesion molecule
Authors: Nakamura Kazuhiro , Manabe Toshiya , Watanabe Masahiko , Mamiya Takayoshi , Ichikawa Ryoichi , Kiyama Yuji , Sanbo Makoto , Yagi Takeshi , Inoue Yoshiro , Nabeshima Toshitaka , Mori Hisashi , Mishina Masayoshi
Published: March 2003

Telencephalin (TLCN) is a cell adhesion molecule selectively expressed in the telencephalon of the mammalian brain. The mutant mice lacking TLCN had no detectable abnormalities in their neural development and synaptic structures. Ablation of TLCN increased the hippocampal long‐term potentiation and its saturation level. The TLCN mutation selectively enhanced the performance of the radial maze and water‐finding tasks, learning tasks with appetitive reinforcers, but not the contextual fear conditioning and Morris water maze tasks with aversive stimuli for conditioning. Furthermore, the TLCN mutant mice showed an increase of prepulse inhibition of the acoustic startle response. These results suggest that TLCN is a determinant of the dynamic range of synaptic plasticity and plays roles in reward‐motivated learning and memory and sensorimotor gating.
Modulation of spinal excitability during observation of hand actions in humans
Authors: Baldissera Fausto , Cavallari Paolo , Craighero Laila , Fadiga Luciano
Published: March 2003

There is growing evidence that observation of actions performed by other individuals activates observer's cortical motor areas. This matching of observed actions on the observer's motor repertoire could be at the basis of action recognition. Here we investigated if action observation, in addition to cortical motor areas, involves also low level motor structures mimicking the observed actions as if they were performed by the observer. Spinal cord excitability was tested by eliciting the H‐reflex in a finger flexor muscle (flexor digitorum superficialis) in humans looking at goal‐directed hand actions presented on a TV screen. We found that, in the absence of any detectable muscle activity, there was in the observers a significant modulation of the monosynaptic reflex size, specifically related to the different phases of the observed movement. The recorded H‐reflex rapidly increased in size during hand opening, it was depressed during hand closing and quickly recovered during object lifting. This modulation pattern is, however, opposite to that occurring when the recorded muscles are actually executing the observed action [Lemon et al. (1995) J. Neurosci., 15, 6145–56]. Considering that, when investigated at cortical level the modulation pattern of corticospinal excitability replicates the observed movements [Fadiga et al. (1995) J. Neurophysiol., 73, 2608–2611], this spinal ‘inverted mirror’ behaviour might be finalised to prevent the overt replica of the seen action.
The central aromatic amino acid DOPA decarboxylase inhibitor, NSD‐1015, does not inhibit l‐DOPA‐induced circling in unilateral 6‐OHDA‐lesioned‐rats
Authors: Treseder Sarah A. , Rose Sarah , Jenner Peter
Published: March 2003

The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3‐hydroxybenzyl hydrazine (NSD‐1015), is widely used to study the neurotransmitter‐like actions of l‐DOPA. However, the effects of NSD‐1015 on l‐DOPA‐induced motor activity are unclear as both increases and decreases have been reported. We now investigate the effects of NSD‐1015 on l‐DOPA‐induced contralateral circling behaviour in 6‐OHDA‐lesioned rats and on striatal levels of l‐DOPA, 3‐O‐methyl‐DOPA (3‐OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) using microdialysis techniques. NSD‐1015 (50–200 mg/kg i.p.) inhibited AADC activity both in the liver and striatum of normal rats. Administration of NSD‐1015 (50–200 mg/kg i.p.), delayed the onset of circling produced by administration of l‐DOPA (25 mg/kg i.p.) and carbidopa (12.5 mg/kg i.p.), suggesting blockade of central AADC activity. However, the duration of the l‐DOPA‐induced circling was prolonged and overall no inhibition of circling behaviour occurred. l‐DOPA (25 mg/kg i.p.) plus carbidopa (12.5 mg/kg i.p.) increased extracellular levels of l‐DOPA, 3‐OMD, dopamine, DOPAC and HVA in the 6‐OHDA‐lesioned striatum. Pretreatment of rats with the central AADC inhibitor, NSD‐1015 (100 mg/kg i.p.), potentiated the increase in dialysate levels of l‐DOPA and 3‐OMD. However, it did not reduce striatal dopamine levels in the 6‐OHDA‐lesioned hemisphere, which were elevated following l‐DOPA administration. The increases in DOPAC and HVA levels were abolished by NSD‐1015 pretreatment. These results suggest that, while NSD‐1015 blocks central AADC activity, it also acts as a monoamine oxidase inhibitor so maintaining striatal dopamine concentration by reducing dopamine metabolism. NSD‐1015, therefore, may not be an appropriate tool for the study of brain AADC activity and for assessing the neuromodulatory role of l‐DOPA.
Stage‐dependent changes in the modulation of spinal nociceptive neuronal activity during the course of inflammation
Authors: Danziger Nicolas , Weil‐Fugazza Jeanne , Le Bars Daniel , Bouhassira Didier
Published: March 2003

Spinal and supraspinal controls can tonically or phasically modulate the output of spinal nociceptive neurons. Alterations of these modulatory systems have been described during the acute stage of inflammation. In the present study in the rat, tonic descending controls were assessed during acute (24–48 h) and chronic (3–4 weeks) stages of monoarthritis of the ankle. The electrophysiological properties of spinal convergent neurons with ankle input were compared before and after spinalization. In a parallel series of experiments, spinal convergent neurons were recorded from the normal side in order to assess the propriospinal and supraspinal inhibitory controls triggered by nociceptive stimulation of the inflamed ankle. Tonic descending inhibition of convergent neurons with input from the inflamed ankle was enhanced during the acute stage and then decreased during the chronic stage of monoarthritis. Contralateral‐induced inhibitions exhibited a similar temporal evolution. Time‐dependent changes in the spinal transmission of nociceptive signals were shown by removing descending modulation in animals with monoarthritis; sensitization of spinal neurons with input from the inflamed ankle was demonstrated during the acute stage of monoarthritis, whereas a crossed transmission between inflamed and normal sides was observed during the chronic stage of the disease. These results show that dynamic and stage‐dependent modifications of descending controls tend to dampen the central changes associated with inflammation.
Taste laterality in the split brain
Authors: Aglioti S. M. , Tassinari G. , Fabri M. , Del Pesce M. , Quattrini A. , Manzoni T. , Berlucchi G.
Published: March 2003

Two patients with corpus callosum resection, one complete and the other sparing the genu and the rostrum, were tested for discrimination of three basic taste stimuli (sour, bitter, salty) applied to the right or left sides of the tongue. Responses were made by pointing with either hand to written words or images of visual objects corresponding to the stimuli, a language‐based discrimination. In both patients, response accuracy was significantly above chance for both hemitongues but there was a significant advantage for the left side. Reaction time was shorter for left stimuli than for right stimuli but the difference was not significant. Eight normal controls matched for age with the patients performed equally well with right and left hemitongue stimuli and so did a third callosotomy patient with sparing of the posterior callosum, including the splenium. Tactile and visual tests showed that the left hemisphere was responsible for language‐based responses in the first two patients. The results confirm and extend previous findings in another callosotomy patient, indicating that: (i) taste information from either side of the tongue can reach the left hemisphere in the absence of the corpus callosum; (ii) the ipsilateral input from the tongue to the left hemisphere is more potent functionally than the contralateral input and (iii) in the normal brain, the corpus callosum, specifically its posterior part including the splenium, appears to equalize the effects of the ipsilateral and contralateral gustatory inputs on the left hemisphere. Taken together with evidence about lateralized taste deficits following unilateral cortical lesions, the results also suggest that the gustatory pathways from tongue to cortex are bilaterally‐distributed with an ipsilateral predominance that may be subject to individual variations.
Altered striatal amino acid neurotransmitter release monitored using microdialysis in R6/1 Huntington transgenic mice
Authors: NicNiocaill B. , Haraldsson B. , Hansson O. , O'connor W. T. , Brundin P.
Published: March 2003

Huntington's disease is an autosomal dominant disease which presents with striatal and cortical degeneration causing involuntary movements, dementia and emotional changes. We employed 16‐week‐old transgenic Huntington mice (R6/1 line developed by Bates and coworkers) that express exon 1 of the mutant human Huntington gene with 115 CAG triplet repeats. At this age, R6/1 mice do not exhibit an overt neurological phenotype nor any striatal neuronal loss. Using microdialysis, we monitored basal and intrastriatal N‐methyl d‐aspartate (NMDA, 100 µm, 15 min)‐ and KCl (100 mm, 15 min)‐induced increases in local aspartate, glutamate and GABA release in halothane‐anaesthetized transgenic mice and wild‐type controls. Basal striatal dialysate glutamate levels were reduced by 42% in R6/1 mice whilst aspartate and GABA levels did not differ from those observed in control mice. Intrastriatal NMDA was associated with significantly greater aspartate (at 15 min) and GABA (at 30 min) levels in the R6/1 mice compared to controls, whilst glutamate release rapidly increased to the same extent in both groups. Intrastriatal KCl was associated with enhanced increases (30 min) in local aspartate and glutamate release in the R6/1 mice above those observed in controls whilst the rapid increase (15 min) in GABA release was similar in both groups. The results provide compelling evidence for specific alterations in both basal, as well as NMDA‐ and KCl‐induced, release of striatal amino acid neurotransmitters in this transgenic model of Huntington's disease, even in the absence of manifest neurodegeneration.
Neuromagnetic evidence for early semantic access in word recognition
Authors: Pulvermüller Friedemann , Assadollahi Ramin , Elbert Thomas
Published: March 2003

Magnetic brain responses recorded in the human magnetoencephalogram (MEG) distinguished between words with different semantics but carefully matched for frequency and length. Multiple recordings from a single subject showed that 100 ms following stimulus onset, significantly stronger neuromagnetic responses were elicited by words with strong multimodal semantic associations than by other word material. At this early processing step, there was a highly significant correlation (0.80) between the magnitude of brain responses to individual words recorded over parieto‐occipital areas and their semantic association strengths. Subsequent to this early difference related to word meaning, additional differences in MEG responses emerged for words from different grammatical categories. Together, these results suggest that word meaning can be reflected by early neuromagnetic brain responses and before the grammatical information about the word is encoded.
The anxiolytic effect of the CRH1 receptor antagonist R121919 depends on innate emotionality in rats
Authors: Keck Martin E. , Welt Tobias , Wigger Alexandra , Renner Ulrich , Engelmann Mario , Holsboer Florian , Landgraf Rainer
Published: March 2003

Hyperactivity of central corticotropin‐releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high‐affinity nonpeptide CRH1 receptor antagonist, displaced 125I‐oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH1 receptor antagonism. In vivo, R121919 significantly inhibited stress‐induced corticotropin release in rats selectively bred for high‐ and low‐anxiety‐related behaviour but displayed anxiolytic effects in high‐anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH1 receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.
Characterization of the metabotropic glutamate receptors mediating phospholipase C activation and calcium release in cerebellar granule cells: calcium‐dependence of the phospholipase C response
Authors: Masgrau Roser , Servitja Joan‐Marc , Young Kenneth W. , Pardo Raul , Sarri Elisabet , Nahorski Stefan R. , Picatoste Fernando
Published: March 2003

In this study we have determined the metabotropic glutamate receptors (mGluRs) involved in the glutamate activation of phospholipase C (PLC) and Ca2+ mobilization in cerebellar granule cells at 9 days in vitro; and studied the Ca2+ modulation of the PLC response. Both PLC activation and Ca2+ signalling were found to be mediated exclusively by the mGluR1 subtype, although both group I mGluRs, mGluR1α and mGluR5, could be detected in cell extracts. Exposure of cells to medium devoid of Ca2+ for various times before agonist stimulation reduced the PLC response, which was quickly recovered following the re‐exposure of cells to Ca2+‐containing medium. The extent of the glutamate response correlated well with changes in the cytosolic Ca2+ concentration. On the other hand, loading of the intracellular Ca2+ stores by a transient depolarization followed by washing in nondepolarizing buffer, allowed glutamate to release stored Ca2+ in the majority of cells and enhanced glutamate activation of PLC. Under such conditions, the absence of extracellular Ca2+ during stimulation and the chelation of cytosolic Ca2+ with BAPTA/AM inhibited both glutamate‐elicited Ca2+ response and PLC activation. Overall, these results indicate that the mGluR‐mediated activation of PLC depends on the presence of extracellular Ca2+ and can be modulated by moderate changes of cytosolic Ca2+. Furthermore, ryanodine reduced PLC stimulation by glutamate in predepolarized cells but not in control cells, suggesting that ryanodine receptors could play a role in the potentiation of the mGluR‐mediated activation of PLC by Ca2+ release in predepolarized cells.
Sympathectomy improves the ear's resistance to acoustic trauma – could stress render the ear more sensitive?
Authors: Horner Kathleen C. , Giraudet Fabrice , Lucciano Michel , Cazals Yves
Published: March 2003

Emotional stress is a phenomenon experienced by many people at some time in their lives. Some of its early manifestations, such as unbearable loudness of ambient sounds and sensations of dizziness, might be linked to inner ear dysfunction. Although the inner ear is supplied with a substantial sympathetic innervation, previous studies have failed to demonstrate any significant functional impact. We show here that in the awake guinea pig and following unilateral ablation of the superior cervical ganglion, the temporary threshold shift induced by a 1‐min exposure to 8 kHz pure tone at 96 dB sound pressure level was reduced by as much as 40 dB. Of interest, the protective effect was bilateral suggesting an intimate relationship between the sympathetic and the olivocochlear efferent systems. The data presented here provide new evidence for a key role for the sympathetic system in modulating temporary threshold shifts following exposure to moderate sound stimulation. This opens new perspectives for investigation of sympathetic control in noise‐induced permanent hearing losses.
The retinal projection to the pregeniculate nucleus in normal and destriate monkeys
Authors: Cowey Alan , Johnson Helen , Stoerig Petra
Published: March 2003

Taking advantage of the segregation of different classes of ganglion cell fibres in the optic tract, we investigated the ganglion cell class that projects to the pregeniculate nucleus (PGN) in the normal macaque monkey (Macaca mulatta and Macaca fascicularis) and following long‐standing removal of striate cortex in one hemisphere. Confining small pellets of horseradish peroxidase and biocytin into ventral or dorsal parts of the tract unilaterally, or placing several pellets throughout the tract, we labelled the retina retrogradely and the PGN anterogradely. Classification of ganglion cells according to soma size and dendritic morphology showed that implants in the dorsal part of the tract labelled predominantly, and perhaps exclusively, Pβ cells, and produced dense anterograde label in the parvocellular lateral geniculate nucleus as well in the PGN. Labelling of the PGN was sparse or absent following implants into the ventral aspect of the tract, which labelled the magnocellular geniculate nucleus anterogradely and chiefly Pα and Pγ cells retrogradely. The finding of a projection to the PGN from Pβ cells has implications for the permanent selective sparing of a subpopulation of these cells after removal of striate cortex and their contribution to wavelength processing in blindsight.
The occ1 gene is preferentially expressed in the primary visual cortex in an activity‐dependent manner: a pattern of gene expression related to the cytoarchitectonic area in adult macaque neocortex
Authors: Tochitani Shiro , Liang Fengyi , Watakabe Akiya , Hashikawa Tsutomu , Yamamori Tetsuo
Published: March 2003

Marker molecules to visualize specific subsets of neurons are useful for studying the functional organization of the neocortex. One approach to identify such molecular markers is to examine the differences in molecular properties among morphologically and physiologically distinct neuronal cell types. We used differential display to compare mRNA expression in the anatomically and functionally distinct areas of the adult macaque neocortex. We found that a gene, designated occ1, was preferentially transcribed in the posterior region of the neocortex, especially in area 17. Complete sequence analysis revealed that occ1 encodes a macaque homolog of a secretable protein, TSC‐36/follistatin‐related protein (FRP). In situ hybridization histochemistry confirmed the characteristic neocortical expression pattern of occ1 and showed that occ1 transcription is high in layers II, III, IVA and IVC of area 17. In addition, occ1 transcription was observed selectively in cells of the magnocellular layers in the lateral geniculate nucleus (LGN). Dual labeling immunohistochemistry showed that the occ1‐positive neurons in area 17 include both γ‐aminobutyric acid (GABA)‐positive aspiny inhibitory cells and the α‐subunit of type II calcium/calmodulin‐dependent protein kinase (CaMKII α)‐positive spiny excitatory cells. With brief periods of monocular deprivation, the occ1 mRNA level decreased markedly in deprived ocular dominance columns of area 17. From this we conclude that the expression of occ1 mRNA is present in a subset of neurons that are preferentially localized in particular laminae of area 17 and consist of various morphological and physiological neuronal types, and, furthermore, occ1 transcription is subject to visually driven activity‐dependent regulation.
Stereotactic recordings of median nerve somatosensory‐evoked potentials in the human pre‐supplementary motor area
Authors: Barba Carmen , Frot Maud , Guénot Marc , Mauguière François
Published: March 2003

Median nerve somatosensory‐evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface‐to‐depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so‐called pre‐SMA. Intracortical responses were analysed in two latency ranges: 0–50 ms and 50–150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20–N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre‐SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50–150 ms latency range, contacts implanted in the pre‐SMA recorded a negative potential in the 60–70 ms latency range which, in five patients, was followed by a positive response peaking 80–110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre‐SMA in the first 50 ms after stimulation, while some potentials peaking in the 60–100 ms after stimulus are likely to originate from this cortical area. The latency of the pre‐SMA responses recorded in our patients supports the hypothesis that the pre‐SMA does not receive short‐latency somatosensory inputs via direct thalamocortical projections. More probably the pre‐SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas.
The isochronic band hypothesis and climbing fibre regulation of motricity: an experimental study
Authors: Fukuda Masaji , Yamamoto Tomoya , Llinás Rodolfo
Published: March 2003

The dynamic organization of the olivocerebellar afferent input to Purkinje cells was examined in rat cerebellar cortex. The distribution of synchronous Purkinje cell complex spike activity was characterized, bilaterally, utilizing multiple electrode recordings in crus IIa folium under ketamine anaesthesia. The results confirmed the existence of rostrocaudal complex spike isochronicity bands with a mediolateral width of 500 µm. For a given band, no finer spatial submicrostructures could be discerned at a first‐order approximation (two‐dimensional projection). Closer analysis determined that isochronicity between bands is not continuous in space but demonstrates discrete discontinuities at the mediolateral boundaries. Principal component multivariate analysis revealed that the first principal component of the spatio‐temporal variance is synchronicity along the rostrocaudal band with a decreased level of coupling in the mediolateral direction at the band boundary. Furthermore, this discrete banding isochronicity is organized by the distribution of feedback inhibition from the cerebellar nuclei on to the inferior olive nucleus. The usual multiple band structure can be dynamically altered to a single wide‐band dynamic architecture, or to other patterns of activity, as may be required by movement coordination.
Bilaterally synchronous complex spike Purkinje cell activity in the mammalian cerebellum
Authors: Yamamoto Tomoya , Fukuda Masaji , Llinás Rodolfo
Published: March 2003

Complex spike activity was simultaneously recorded from 96 Purkinje cells in the rat cerebellar cortex. Rostrocaudal complex spike synchronicity bands were studied in crus I, IIa and IIb and in vermal lobule 6c. Detailed analysis in crus IIa revealed that complex spike activity was staggered sequentially with a 20–50 cm/sec ‘propagation velocity’ in the mediolateral direction, and that such activity was bilaterally synchronous. The ‘propagation’ of complex spike activity was symmetrical between right and left crus IIa. Temporally, the neurons that aligned in the rostrocaudal direction typically generated complex spikes close to simultaneously. The correlation of complex spike firing was high between crus IIa and crus IIb, moderate between crus IIa and vermis 6c, and relatively low between Purkinje cells in crus I and crus IIa. These results indicate that, whilst discrete boarders exist between different isochronicity bands, these bands do communicate with each other in the mediolateral direction via slow ‘propagation waves’ that loosely bind their activity. The results indicate that the olivocerebellar system is organized, bilaterally, to take advantage of the timing signals generated at the inferior olive nucleus.
Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A
Authors: Pasterkamp R. Jeroen , Anderson Patrick N. , Verhaagen Joost
Published: March 2003

We have investigated the hypothesis that the chemorepellent Semaphorin3A may be involved in the failure of axonal regeneration after injury to the ascending dorsal columns of adult rats. Following transection of the thoracic dorsal columns, fibroblasts in the dorsolateral parts of the lesion site showed robust expression of Semaphorin3A mRNA. In addition, dorsal root ganglion (DRG) neurons with projections through the dorsal columns to the injury site persistently expressed both Semaphorin3A receptor components, neuropilin‐1 and plexin‐A1. These ascending DRG collaterals failed to invade scar regions occupied by Semaphorin3A‐positive fibroblasts, even in animals which had received conditioning lesions of the sciatic nerve to enhance regeneration. Other axon populations in the dorsal spinal cord were similarly unable to penetrate Semaphorin3A‐positive scar tissue. These data suggest that Semaphorin3A may create an exclusion zone for regenerating dorsal column fibres and that enhancing the intrinsic regenerative response of DRG neurons has only limited effects on axonal regrowth. Tenascin‐C and chondroitin sulphate proteoglycans were also detected at the injury site, which was largely devoid of central nervous system (CNS) myelin, showing that several classes of inhibitory factors, including semaphorins, with only partially overlapping spatial and temporal patterns of expression are in a position to participate in preventing regenerative axonal growth in the injured dorsal columns. Interestingly, conditioning nerve injuries enabled numerous ascending DRG axons to regrow across areas of strong tenascin‐C and chondroitin sulphate proteoglycan expression, while areas containing Semaphorin3A and CNS myelin were selectively avoided by (pre)primed axonal sprouts.
The synthetic cannabinoid WIN55212‐2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies
Authors: Porcella Anna , Maxia Chiara , Gessa Gian Luigi , Pani Luca
Published: March 2003

The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212–2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development.
The anabolic‐androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain
Authors: Kindlundh Anna M. S. , Lindblom Jonas , Bergström Lena , Wikberg Jarl E. S. , Nyberg Fred
Published: March 2003

In recent years a male group of anabolic‐androgenic steroid misusers has been identified to share socio‐demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic‐androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D1‐like and D2‐like receptors were evaluated by autoradiography. Specific binding of D1‐like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D2‐like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.