bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Organization of Auditory Cortex in the Mongolian Gerbil (Meriones unguiculatus) II. Tonotopic 2‐Deoxyglucose
Authors: Scheich Henning , Heil Peter , Langner Gerald
Published: April 2006

The tonotopic organization of the auditory cortex in the Mongolian gerbil was mapped with 2‐deoxyfluoro‐D‐glucose (2DG) using narrow‐band frequency‐modulated tones of different centre frequency (FM tones) and tones periodically alternating between two different frequencies (alternating tones) as stimuli. Continuous tone bursts of a constant frequency and repetition rate were used in initial experiments. Continuous tones produced 2DG patterns similar to those observed in animals that were not specifically stimulated. With tone bursts of constant frequency and repetition rate variable patterns were observed, some of which could be interpreted only in retrospect in the light of results obtained with FM tones and alternating tones. These stimuli, in contrast, produced differential metabolic responses which in conjunction with 2DG data from monaural animals and electrophysiological data made it possible to distinguish a primary auditory field AI with its dorsal region Aid, an anterior auditory field AAF, a ventral field V, a dorsoposterior field DP and a ventroposterior field VP, a dorsal field D, and in addition an anteroventral field AV. In the largest field (AI) and the smaller rostrally adjacent field AAF, frequency‐specific dorsoventral bands of labelling (isofrequency contours) were mapped quantitatively. Bands shifted as a function of frequency relative to each other and to an independent spatial reference line in the lateral hippocampus. Spatial analysis of the single bands obtained with FM tones, and of the double bands obtained with alternating tones in both fields, revealed roughly mirror‐imaged tonotopic maps of AI and AAF. In AI the progression from low to high frequencies was from caudal to rostral and in AAF the gradient was reversed, leading to a common high‐frequency border of the two fields. In AI, the spatial resolution for frequencies below 16 kHz was in similar intervals per octave and higher for frequencies below 1 kHz. AI showed a somewhat higher spatial resolution for frequencies (at least below 1 kHz) as well as longer isofrequency contours than AAF. The 2‐deoxyglucose patterns provided average tonotopic maps and topological data on various fields, as well as reliable landmarks in the gerbil's auditory cortex.
PDGF‐BB Exerts Trophic Activity on Cultured GABA Interneurons from the Newborn Rat Cerebellum
Authors: Smits A. , Ballagi A. E. , Funa K.
Published: April 2006

Platelet‐derived growth factor (PDGF) is a well known mitogen for mesenchyme‐derived cells and glial cells. Its presence in neuronal cells of the central nervous system has only recently been described. We have shown earlier that neurons of newborn rat brains in culture express PDGF β‐receptors and that PDGF‐BB, a homodimer of PDGF B‐chain, increases survival and promotes neurite outgrowth of newborn cerebellar cells (Smits et al., Proc. Natl Acad. Sci. USA, 88, 8159 – 8163, 1991). In this study, the effects of PDGF on early postnatal rat cerebellar cells were further explored. By using chemically defined serum‐free medium, we have established primary cell cultures of rat cerebella (postnatal day 4 – 5) containing 70 – 80% neuronal cells. During the first 10 days in vitro, no difference in total cell number was found between PDGF‐BB‐treated and untreated cultures. After this time period, however, increased survival of the PDGF‐BB‐treated cells was found. Within the first 10 days in vitro, the addition of PDGF‐BB to the cultures resulted in a relative increase in survival of interneurons expressing glutamic acid decarboxylase (GAD), the GABA biosynthetic enzyme. Moreover, addition of PDGF‐BB in the untreated cell culture resulted in a rapid increase of GAD mRNA. These results show that PDGF‐BB acts as a trophic factor on GABAergic interneurons of the cerebellum by up‐regulating GAD synthesis and prolonging the survival of these cells. Furthermore, in situ hybridization revealed that there are scattered cells present in the early postnatal cerebellum that express PDGF β‐receptor mRNA. The localization of these cells in the molecular layer and in the proximity of the internal granular layer corresponds to that of GABAergic interneurons in the developing cerebellum.
The High Sensitivity to Rotenone of Striatal Dopamine Uptake Suggests the Existence of a Constitutive Metabolic Deficiency in Dopaminergic Neurons From the Substantia Nigra
Authors: Marey‐Semper Isabel , Gelman Michèle , Lévi‐Strauss Matthieu
Published: April 2006

The toxicity of the 1‐methyl‐4‐phenylpyridinium ion (MPP+), an inhibitor of complex I of the respiratory chain, on nigrostriatal dopaminergic neurons contrasts with its relative inefficiency towards other catecholaminergic cell populations in spite of their ability to accumulate this neurotoxin through their high‐affinity uptake system. A constitutive metabolic deficiency of the nigrostriatal dopaminergic neurons could account for their particular vulnerability to MPP+. In order to substantiate this hypothesis, we compared the inhibitory effects of rotenone, an inhibitor of mitochondrial oxidative phosphorylation, on the uptake of dopamine, serotonin, noradrenaline and GABA in mouse striatal synaptosomes, and of dopamine, serotonin and GABA in cultured mesencephalic neurons. In both preparations, the uptake of dopamine was much more affected than that of other neurotransmitters by rotenone. This result was confirmed using two other unrelated inhibitors of oxidative phosphorylation. Moreover, dopamine uptake in synaptosomes from the dorsolateral striatum was more sensitive to rotenone than uptake in synaptosomes from the nucleus accumbens. This indicates that intrinsic metabolic properties of the nigrostriatal dopaminergic neurons may explain the strong inhibition by rotenone of striatal dopamine uptake. Altogether, these results suggest that a constitutive metabolic deficiency could account, at least in part, for the selective vulnerability of the nigrostriatal dopaminergic pathway to the action of the neurotoxin MPP+.
Enhancement of AMPA‐mediated Synaptic Transmission by the Protein Phosphatase Inhibitor Calyculin A in Rat Hippocampal Slices
Authors: Figurov Alexander , Boddeke Hendrick , Muller Dominique
Published: April 2006

Using the phosphatase inhibitor calyculin A, we have examined the influence of phosphorylation on synaptic transmission and plasticity in rat CA1 hippocampal slices. Bath application of 0.5 – 1 μM of calyculin A resulted in an increase of 42.6 ±2.9% in synaptic responses. The effect produced by calyculin A was not accompanied by changes in fibre volley, was not associated with changes in paired‐pulse facilitation, and could be reproduced by intracellular injection of the compound, thereby indicating a postsynaptic action. Also, the synaptic enhancement produced by calyculin A was expressed only by potentials mediated by amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors, but not by the NMDA responses recorded in the presence of the AMPA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and low magnesium. The effect of calyculin A could be prevented by KN‐62, an inhibitor of calcium/calmodulin‐dependent protein kinase II. Long‐term potentiation could still be induced in the presence of calyculin A, but the effect of the compound was slightly reduced on potentiated compared with control pathways. These results indicate that calyculin A can selectively increase the efficacy of AMPA receptor‐mediated synaptic transmission at excitatory synapses.
Confocal Microscopy and Computer‐assisted Image Reconstruction of Astrocytes in the Mammalian Retina
Authors: Rungger‐Brändle Elisabeth , Messerli J. Marius , Niemeyer Günter , Eppenberger Hans M.
Published: April 2006

The distribution of astrocytes in the vascularized retina of pigs, rats and cats was investigated by confocal microscopy and computer‐assisted image processing. In whole mounts, immunocytochemical identification was done by staining astrocytes for glial fibrillary acidic protein (GFAP), and blood vessels for α‐smooth muscle actin or collagen IV. Double‐staining was followed through consecutive optical sections and made it possible to precisely align the two markers in the inner retina. The resulting computer‐assisted image reconstructions revealed asymmetric ensheathment of blood vessels by GFAP‐positive fibres. The ultrastructural basis for this asymmetry, as studied by electron microscopy, was found to be different in pigs and cats. In the pig, astrocytes firmly ensheathed the vessel circumference, but glial filaments were much more abundant on the vitreal and lateral than on the scleral side. By contrast, in the cat astrocytes were generally confined to regions occupied by axonal bundles and constituted only part of the vascular glia limitans, else formed by Müller cells. Moreover, our observations unambiguously showed that individual astrocytes maintained simultaneous contact with axons and blood vessels and lined the vitreous body. The physical links provided by astrocytes suggest that they are able to function as central communicating elements between ganglion cells, the vasculature and the vitreous body.
Trophic Factors Produced by Retinal Cells Increase the Survival of Retinal Ganglion Cells In Vitro
Authors: de Araujo Elizabeth Giestal , Linden Rafael
Published: April 2006

The naturally occurring neuron death of normal development has been shown to depend on trophic factors produced and released by target cells. It has also been shown that the afferent supply and local interactions play a role in the control of this degenerative phenomenon. We studied the effect of trophic factors produced by intrinsic retinal cells on the survival of retinal ganglion cells in vitro. Retinae of newborn hooded rats were retrogradely labelled with horseradish peroxidase injected into the superior colliculus to permit the identification of retinal ganglion cells in culture. We tested the effect of conditioned media either from aggregates or from explants of retinal cells from neonatal rats on the survival of ganglion cells in vitro. Our results showed that both conditioned media increased the survival of these cells. The trophic activity was dose‐dependent, was maintained after dialysis against a 12 kDa membrane, was abolished by heating at 56°C for 30 min, and was not found in conditioned medium from cerebral cortical explants. Conditioned medium obtained without fetal calf serum presented the same trophic effect. These results suggest that the local control of developmental neuron death by intrinsic retinal cells may be mediated by neurotrophic factors.
Glutamate Receptors on type I Vestibular Hair Cells of Guinea‐pig
Authors: Devau Gina , Lehouelleur Jacques , Sans Alain
Published: April 2006

Afferent nerve calyces which surround type I vestibular hair cells (VHCI) have recently been shown to contain synaptic‐like vesicles and to be immunoreactive to glutamate antibodies. In order to understand the physiological significance of these observations, the presence of glutamate receptors on type I vestibular sensory cells has been investigated. The effect of excitatory amino acids applied by iontophoresis was examined by spectrofluorimetry using fura‐2 sensitive dye. Glutamate application caused a rapid and transient increase in intracellular calcium concentration ([Ca2+]i), in a dose‐dependent manner. The ionotropic glutamate receptors agonists N‐methyl‐d‐aspartic acid (NMDA), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and quisqualic acid (QA) induced an increase of [Ca2+]i. The NMDA receptor antagonist 2‐amino‐5‐phosphonovaleric acid and the AMPA receptor antagonist 6,7‐dinitro‐quinoxaline‐2,3‐dione partially blocked the glutamate response, by 39 ± 10 and 53 ± 11% respectively. Metabotropic receptors were also revealed by the specific agonist trans‐1‐amino‐cyclopentyl‐1,3‐dicarboxylate. The presence of different glutamate receptors on the VHCI membrane suggests two kinds of feedback, (i) At the base of the sensory cell, autoreceptors may locally control the synaptic transmission, (ii) At the apex, postsynaptic receptors may modulate sensory transduction from glutamate release at the upper part of the afferent nerve calyx. These feedbacks suggest presynaptic modulation of the vestibular hair cell response which could affect its sensitivity.
Elevated Seizure Threshold and Impaired Spatial Learning in Transgenic Mice with Putrescine Overproduction in the Brain
Authors: Halonen T. , Sivenius J. , Miettinen R. , Halmekytö M. , Kauppinen R. , Sinervirta R. , Alakuijala L. , Alhonen L. , MacDonald E. , Jänne J. , Riekkinen P. J.
Published: April 2006

We have studied the role of putrescine by using transgenic mouse lines overexpressing the human ornithine decarboxylase gene in most of their tissues. The aberrant expression of the transgene is most strikingly manifested in the brain, leading to an increase of up to 20‐fold in putrescine content. We report that the transgenic mice with grossly elevated putrescine in all brain regions analysed (cortex, striatum, hippocampus and cerebellum) showed a significantly elevated seizure threshold to chemical and electrical stimuli, and impaired performance in spatial learning and memory tests. The view that putrescine may be primarily responsible for these changes was supported by the fact that the concentrations of the major neurotransmitter amino acids, glutamate and GABA in the brain, were not changed in the transgenic animals, and by the finding that a further increase in brain putrescine, achieved by inhibition of the catabolism of l‐ornithine, appeared to provide additional protection against electroshock‐induced seizures. These results suggest that the commonly observed increase in ornithine decarboxylase activity and the massive increase in brain putrescine in connection with neuron damage is a neuroprotective measure rather than a cause of the damage.
aFGF, bFGF and flg mRNAs Show Distinct Patterns of Induction in the Hippocampus Following Kainate‐induced Seizures
Authors: Bugra Kuyas , Pollard Hélène , Charton Gérard , Moreau Joëlle , Ben‐Ari Yezekiel , Khrestchatisky Michel
Published: April 2006

We report that kainic acid‐induced seizures lead to marked increases in mRNAs encoding basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) and fig, one of their receptors, in the rat hippocampus. Anticonvulsant pretreatment inhibits the up‐regulation of these mRNAs. The observed increase in fig mRNA levels involves the pyramidal cells of all hippocampal subfields and the granular ceils of the dentate gyrus. The increased expression of aFGF and bFGF mRNAs is limited to neuron populations that are resistant to seizure‐induced injury, the granular cells of dentate gyrus and pyramidal cells of CA1 region, respectively. The results suggest that the increase in the FGFs and fig may play pivotal roles in neuron survival and in long‐term changes occurring in the hippocampus following seizure activity.
Early Postnatal Changes in the Somatodendritic Morphology of Ankle Flexor Motoneurons in the Rat
Authors: Dekkers Joanna , Becker David L. , Cook Jeremy E. , Navarrete Roberto
Published: April 2006

The development of locomotor function in the rat spans the first 3 postnatal weeks. We have studied morphological features of the soma and dendrites of motoneurons innervating the physiological flexor muscles of the ankle, tibialis anterior and extensor digitorum longus, by intracellular injection in vitro between the first and ninth postnatal days. We obtained serial optical sections of 96 adequately filled motoneurons in whole‐mounted hemisected spinal cords by confocal microscopy, projected them onto a single plane and analysed them morphometrically. On the day after birth, the somatodendritic surfaces of most such motoneurons were covered in growth‐associated spiny, thorny or hair‐like appendages. These had disappeared from the soma by the fourth postnatal day and from most proximal dendrites by day 7, but were still common distally on day 9. During this period there was little or no net growth of either the soma (which was still much smaller than in the adult) or the dendritic tree. A dorsal dendritic bias was present and ‘sprays’ of long, loosely bundled dorsal dendrites were often seen. The mean number of primary dendrites remained constant at about eight, and their combined diameter was already significantly correlated with mean soma diameter, as in the adult cat. Thus, the critical neonatal period during which these ankle flexor motoneurons are known to change their electrophysiological properties and to be particularly sensitive to interference with neuromuscular interaction is characterized by major changes in the neuronal surface, presumably linked to synaptogenesis.
Excitatory Amino Acid Receptors Participate in Synaptic Transmission of Visual Responses in the Superficial Layers of the Cat Superior Colliculus
Authors: Binns K. E. , Salt T. E.
Published: April 2006

The contribution of NMDA and non‐NMDA receptors to visual synaptic transmission in the superficial layers of the superior colliculus of the cat has been studied using extracellular recording and iontophoretic techniques. Neuronal responses to natural visual stimulation and the ejection of NMDA and AMPA were observed in the absence and presence of the antagonists CNQX, CPP and AP5. CNQX routinely reduced the responses to visual stimulation at ejection currents which selectively blocked the responses to AMPA but not those to NMDA. Agonist selective ejection currents of CPP and AP5 also reduced visual responses of most SC neurons, but there was a substantial majority whose visual responses were resistant to these antagonists. Neurons with CPP/AP5 resistant visual responses were more commonly found 750–1000 μm from the dorsal surface of the SC. The data indicate that, while non‐NMDA receptors are heavily involved in visual synaptic transmission in the superficial SC, the involvement of NMDA receptors varies with recording depth.
Regulation of Ciliary Neurotrophic Factor in Cultured Rat Hippocampal Astrocytes
Authors: Rudge John S. , Morrissey Donna , Lindsay Ronald M. , Pasnikowski Elizabeth M.
Published: April 2006

Ciliary neurotrophic factor (CNTF) is a pleiotrophic cytokine which is detectable only at very low levels in the intact adult rat CNS, but following an aspirative lesion to the dorsal hippocampus and overlying cortex, CNTF mRNA levels are dramatically up‐regulated in reactive astrocytes. In cultured rat hippocampal astrocytes, CNTF mRNA levels are high, similar to the levels in reactive astrocytes in vivo, but are strongly suppressed after administration of isoproterenol and forskolin, which stimulate the production of intracellular cyclic AMP, induce marked morphological change in the astrocytes and up‐regulate glial fibrillary acidic protein mRNA and nerve growth factor mRNA in these cells. Following a single administration of forskolin to cultured astrocytes, suppression of CNTF mRNA was sustained for up to 7 days. A similar down‐regulation was observed with the endogenous adrenergic agonists noradrenaline and adrenaline as well as, to a lesser extent, dopamine and adenosine. Down‐regulation of CNTF mRNA resulted in a gradual reduction in the level of CNTF protein within the astrocytes. A single addition of forskolin or isoproterenol resulted in a drop in CNTF protein levels to 29 and 52% of control levels respectively after 9 days in vitro, although the rate of turnover of CNTF remained the same. Down‐regulation of CNTF mRNA in cultured hippocampal astrocytes by adenylyl cyclase activation was quite specific, as a wide range of growth factors, cytokines and neurotransmitters had little or no effect upon CNTF mRNA levels.
Effects of Apomorphine and L‐Methionine Sulphoximine on the Release of Excitatory Amino Acid Neurotransmitters and Glutamine in the Striatum of the Conscious Rat
Authors: Exposito Inmaculada , Sanz Belén , Porras Alberto , Mora Francisco
Published: April 2006

The effects of apomorphine, a D1‐, D2‐dopamine receptor agonist, on the extracellular concentrations of excitatory amino acids, glutamic and aspartic acids, and on that of their precursor, glutamine, were investigated using an intracerebral perfusion system. Apomorphine produced a concentration‐related rise in glutamic acid concentration in cerebral perfusates (P < 0.01) whereas only the highest concentration of apomorphine (3 × 10‐3μg/μl) increased the concentration of aspartic acid (P < 0.05). These effects were seen in the sample taken at the same time as the apomorphine injection. The rise in glutamine concentration (P < 0.01) produced by apomorphine continued for 10 min beyond perfusion with apomorphine. These effects were attenuated by previous injections of a D1‐, D2‐dopamine receptor blocker. To investigate further the release of glutamine, the glutamine synthetase inhibitor L‐methionine sulphoximine (MSO) was injected intracerebrally before apomorphine perfusion. After MSO pre‐injection, the extracellular concentration of glutamine decreased (P < 0.01) to near zero concentrations. In MSO‐treated animals, apomorphine did not induce the release of glutamic acid, aspartic acid or glutamine. These results indicate a role for dopamine in the release of excitatory amino acids and glutamine in the neostriatum of the rat. A possible volumetric interaction between dopamine and glutamic acid as well as the hypothesis of a striato‐pallido‐thalamo‐cortico‐striatal feedback loop are discussed.
Reciprocal Connections of the Motor Neocortical Area with the Contralateral Thalamus in the Hedgehog (Erinaceus europaeus) Brain
Authors: Dinopoulos A.
Published: April 2006

Horseradish peroxidase unilateral injections in various neocortical areas (prefrontal, somatosensory, auditory, visual) of the hedgehog (Erinaceus europaeus) brain resulted in labelling of nuclei in the ipsilateral thalamus known from studies in other species and in the hedgehog to project to these areas. However, injections in the motor area resulted in retrograde and anterograde labelling of nuclei in both the ipsilateral and contralateral thalamus. These nuclei included the ventral lateral nucleus (VL), the intralaminar nuclei (ILN), the mediodorsal nucleus (MD) and midline nuclei. Large unilateral injections located mainly laterally in the thalamus labelled cells, contralaterally, in the ventral lateral geniculate nucleus, the intergeniculate leaflet and the reticular nucleus of the thalamus but never in VL, ILN and MD. The present results confirm previously described bilateral thalamocortical projections from the VL to the somatosensorimotor area in this species (Regidor and Divac, Brain Behav. Evol., 39, 265–269, 1992) and in addition demonstrate that (i) bilateral thalamocortical projections are established preferentially with the motor area, (ii) several nuclei are involved in such connections, (iii) these connections are reciprocal and topographically organized, and (iv) labelling in the contralateral thalamus observed in the present study is not a result of transneuronal transport of the tracer through thalamothalamic connections. This organization is unique among mammals and supports previous anatomical and electrophysiological findings, on the basis of which it has been suggested that the hedgehog retains a primitive character in neocortical and thalamic evolution.
Exposure to Kainic Acid Mimics the Effects of Axotomy in Cerebellar Purkinje Cells of the Adult Rat
Authors: Rossi Ferdinando , Borsello Tiziana , Strata Piergiorgio
Published: April 2006

We have investigated the long‐term structural changes which affect Purkinje cells exposed to a single dose of kainic acid. Following intraparenchymal injection of the excitotoxin in the cerebellar cortex (1 μ1 of a 1 mg/ml solution), Purkinje cells which survived within the lesioned area or close to its edges showed remarkable axonal abnormalities, involving the formation of torpedoes, hypertrophy of recurrent collaterals and atrophy of the corticofugal portion of the axon. In addition, their dendritic trees were often affected by conspicuous regressive alterations. The climbing fibres contacting these Purkinje cells were characterized by thick perisomatic plexuses, whereas their peridendritic branches were atrophic. The dendrites innervated by such atrophic olivary arbours were studded with huge numbers of newly formed spines. These alterations were already present a few days after kainic acid administration and persisted for the total period of observation of 6 months after the lesion. The remarkable similarity between the abnormalities of Purkinje cells exposed to kainic acid and those observed after axotomy indicates that in these two conditions common mechanisms determine analogous long‐lasting modifications in the affected neurons. It is proposed that kainic acid‐induced intracellular calcium overload disrupts cytoskeletal components and impairs axonal transport, thus depriving the affected Purkinje cells of retrograde trophic influences from their target neurons. As a consequence the affected neurons undergo long‐lasting regressive modifications and compensatory remodelling phenomena.
Increased Expression of the Growth‐associated Protein GAP‐43 in the Myelin‐free Rat Spinal Cord
Authors: Kapfhammer Josef P. , Schwab Martin E.
Published: April 2006

In the normal central nervous system (CNS) the regional expression of the growth‐associated protein GAP43 is complementary to the pattern of myelination. This has led us to suspect that myelin‐associated neurite growth inhibitors might contribute to the suppression of GAP‐43 expression by suppressing sprouting and plastic changes of synaptic terminals in myelinated CNS areas. In order to study the relationship between myelination and GAP‐43 expression more directly, we experimentally prevented myelination of the lumbar spinal cord of rats through neonatal X‐irradiation. The GAP‐43 protein expression in myelin‐free spinal cords was analysed by immunohistochemistry and immunoblotting and compared to age‐matched normal spinal cords. We found that in the absence of myelination, GAP‐43 expression is strongly increased in the spinal cord of 4‐week‐old rats. GAP‐43 was most strongly expressed in descending fibre tracts, where expression in the normal spinal cord is very low. In grey matter the typical regional pattern of GAP‐43 expression did not develop; instead GAP‐43 expression was high in all regions of the spinal cord. The overall pattern of myelination and GAP‐43 expression in the myelin‐free cord resembled that of early postnatal stages. This indicates that the regional down‐regulation of GAP‐43 expression during normal postnatal development did not occur in the myelin‐free areas. Our results support the hypothesis that neurite growth inhibitors from oligodendrocytes and CNS myelin suppress sprouting and plastic changes of synaptic terminals in the normal CNS and are thereby involved in regulating the stability of neural connections.
Rostrocaudal Subregional Differences in the Response of Enkephalin, Dynorphin and Substance P Synthesis in Rat Nucleus Accumbens to Dopamine Depletion
Authors: Voorn Pieter , Docter Gerrit J. , Jongen‐Rêlo Ana L. , Jonker Allert Jan
Published: April 2006

Quantitative in situ hybridization histochemistry was used to examine the effects of unilateral 6–hydroxydopamine lesions of the ascending dopaminergic fibres on levels of mRNA encoding the neuropeptides enkephalin, dynorphin and substance P in subregions of the nucleus accumbens. The nucleus accumbens was divided into quadrants and changes in mRNA were measured along the rostrocaudal extent of the nucleus. Two weeks after the lesion an increase was found in enkephalin mRNA in the lesioned side compared to the non‐lesioned side, whereas a decrease was observed for dynorphin and substance P mRNA. The changes in mRNA levels differed from quadrant to quadrant and were not uniformly distributed along the rostrocaudal axis. Both types of changes, i.e. increase and decrease, were much higher in rostral parts of the nucleus than in caudal parts, indicating regional differences in the effects of blockade of the dopaminergic neurotransmission. The lesion‐induced increases and decreases in mRNA levels occurred in both the shell and the core subregions of the nucleus accumbens and were not specifically related to either of these areas. Factors are discussed that may contribute to the rostrocaudal gradient in the changes of enkephalin, substance P and dynorphin mRNA levels. On the basis of their afferent and efferent connections, the rostral and caudal parts of the nucleus accumbens are considered to be involved in different functions. The present results suggest that dopamine depletion may affect these functions in a differential manner.
The Effects of Archistriatal Lesions on One‐trial Passive Avoidance Learning in the Chick
Authors: Lowndes M. , Davies D. C.
Published: April 2006

The avian archistriatum, part of which may be homologous with the mammalian amygdala, has been implicated in fear and avoidance behaviour. There is also evidence to suggest its involvement in learning. One‐trial passive avoidance learning (PAL) has been used extensively to study memory formation in the chick. Young chicks will peck spontaneously at a small, visually conspicuous bead. If the bead has been coated with an aversive substance, the chicks show a disgust response and learn in a single trial not to peck a similar bead on subsequent presentation. Successful acquisition of this one‐trial PAL task involves the formation of a learned association between the bead and a noxious taste, followed by the expression of an avoidance response. In view of the possible involvement of the archistriatum in avoidance and learning behaviour, its role in one‐trial PAL was investigated by ablation. Bilateral electrolytic lesions of the entire archistriatum prevented the acquisition of the one‐trial PAL task. Neither bilateral lesions of the lateral cerebral area nor sham operation affected learning. The impairment of one‐trial PAL caused by archistriatal lesions was not due to effects on the visual or motor components of pecking behaviour. The archistriatum could therefore be directly involved in memory formation. It could also be involved in the organization of avoidance behaviour associated with the task, or it could form part of a circuit linking two other forebrain regions previously implicated in one‐trial PAL, the intermediate part of the medial hyperstriatum ventrale and the lobus parolfactorius.
Positive Feedback between Acetylcholine and the Neurotrophins Nerve Growth Factor and Brain‐derived Neurotrophic Factor in the Rat Hippocampus
Authors: Knipper Marlies , da Penha Berzaghi Maria , Blöchl Andrea , Breer Heinz , Thoenen Hans , Lindholm Dan
Published: April 2006

In the rat hippocampus, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) are synthesized by neurons in an activity‐dependent manner. Glutamate receptor activation increases whereas GABAergic stimulation decreases NGF and BDNF mRNA levels. Here we demonstrate that NGF and BDNF mRNA and NGF protein are up‐regulated in the rat hippocampus by the activation of muscarinic receptors. Conversely, NGF and BDNF enhance the release of acetylcholine (ACh) from rat hippocampal synaptosomes containing the nerve endings of the septal cholinergic neurons. NGF also rapidly increases the high‐affinity choline transport into synaptosomes. The reciprocal regulation of ACh, NGF and BDNF in the hippocampus suggests a novel molecular framework by which the neurotrophins might influence synaptic plasticity.
The NMDA Receptor Antagonist CPP Suppresses Long‐term Potentiation in the Rat Hippocampal — accumbens Pathway In Vivo
Authors: Feasey‐Truger K. J. , Ten Bruggencate G.
Published: April 2006

Excitation of afferent fibres originating in the ventral subiculum of the hippocampus through stimulation of the fimbria elicits field potentials in the nucleus accumbens. When recorded in the dorsomedial aspect of the nucleus accumbens, the evoked field responses consisted of an early, negative‐going component (Nl) with a peak latency of 8–10 ms, followed by a second negative‐going peak (N2) with a latency of 22–24 ms. The N1 response reflects monosynaptic activation of nucleus accumbens neurons; the N2 component appears to be polysynaptic in origin. In control rats, high‐frequency stimulation of the fimbria (three trains at 250 Hz, 250 ms, delivered at 50 min intervals) resulted in a long‐lasting potentiation of both the N1 and N2 components. The magnitude of potentiation exhibited by the polysynaptic N2 response was typically greater than that of the monosynaptically evoked N1 response. Following delivery of the first train, the amplitude of the N1 and N2 components was increased by ‐20 and 50% respectively. Administration of the competitive N‐methyl‐d‐aspartate (NMDA) receptor antagonist 3‐[(±)‐2‐carboxypiperazin‐4‐yl]‐propyl‐1‐phosphonic acid (CPP, 10 mg/kg i.p.) had no significant effects on the evoked nucleus accumbens responses. High‐frequency stimulation failed to produce a significant increase in the amplitude of either the N1 or the N2 response when delivered 45–60 min after CPP administration. To test whether the suppressant effects of CPP were time‐dependent, two further high‐frequency trains were applied 90 and 180 min after administration of the drug. Significant increases in the amplitude of the N1 and N2 components were observed only after the third train, delivered 180 min after CPP injection. These results demonstrate that high‐frequency stimulation of hippocampal afferents to the nucleus accumbens induces LTP in both a monosynaptic and a polysynaptic pathway. In both cases, the induction of LTP is suppressed in a time‐dependent manner by the competitive NMDA receptor antagonist CPP. Thus, NMDA receptor activation appears to be prerequisite for the induction of LTP in the hippocampus ‐ accumbens pathway.
Immunohistochemical Characterization of the Shell and Core Territories of the Nucleus Accumbens in the Rat
Authors: Jongen‐Rêlo Ana L. , Voorn Pieter , Groenewegen Henk J.
Published: April 2006

The nucleus accumbens in the rat has been parcelled into shell and core subdivisions. Despite accumulating evidence for such a division of the nucleus accumbens, these territories have not been delineated throughout the rostrocaudal extent of the nucleus. In the present study, an attempt has been made to delineate the shell and core using the distribution of calcium‐binding protein immunoreactivity, substance P immunoreactivity and acetylcholinesterase activity in transverse and horizontal sections through the nucleus accumbens. It was found that the pattern of calcium‐binding protein immunoreactivity provides the most unequivocal criterion to divide the nucleus accumbens into a ventral and medial, peripheral shell displaying low to moderate immunostaining, and a more laterally and dorsally located, strongly stained inner core. In most parts of the nucleus, borders seen in the calcium‐binding protein immunoreactivity pattern can also be recognized in the distributions of substance P immunoreactivity and acetylcholinesterase activity. It is concluded that the shell occupies most of the rostral part of the nucleus accurnbens, whereas rostrally the core is represented only in the most lateral part. Differences in staining intensities for all three markers indicate that both the shell and core have a heterogeneous structure. Patterns of connectivity appear to support the division of the nucleus accumbens as indicated by calcium‐binding protein immunoreactivity in the present study.
The Entorhinal Cortex and a Delayed Non‐matching‐to‐place Task in Mice: Emphasis on Preoperative Training and Presentation Procedure
Authors: Cho Yoon H. , Jaffard Robert
Published: April 2006

This study examined the effects of ibotenate lesions of the entorhinal cortex (EC) on performance of a spatial recognition memory task, the delayed non‐matching‐to‐place task (DNMTP), varying in level of difficulty according to the number of interpolated arm visits between sample‐place presentation and subsequent recognition in mice. Results of experiment 1, designed to test the rate of acquisition of the task, showed that experimental animals were impaired in the basic non‐matching task. However, with further training they were able to learn the task. Impairments were also observed when the amount of interpolating information inserted was gradually increased, and then all problem difficulties were pseudorandomly tested. There was no measurable recovery of function over time when the animals were retested on the task ∼1 month later. Experiment 2 showed that the animals that received extensive training on the task prior to lesions of the EC were only transiently impaired in the DNMTP task. These data suggest that the EC plays an important role in acquisition rather than retention of the spatial recognition memory task.
Corticosteroid Receptor Antagonists are Amnestic for Passive Avoidance Learning in Day‐old Chicks
Authors: Sandi Carmen , Rose Steven P. R.
Published: April 2006

Glucocorticoids can modulate behavioural processes and neural plasticity. They are released during learning situations and can trigger neural actions through binding to brain receptors. We hypothesized that a glucocorticoid action could play a critical role in the mechanisms involved in long‐term memory formation. In order to test this hypothesis, chicks were trained on a passive avoidance learning task and given bilateral intracerebral injections of selective mineralocorticoid (RU‐28318) or glucocorticoid (RU‐38486) receptor antagonists. The results showed that both antagonists alter information processing when injected prior to the training session. Possible state‐dependent effects were discharged. Further experiments evaluating possible effects of the antagonists on concomitant aspects of the learning situation (such as novelty reaction and pecking pattern) indicated that, as opposed to the glucocorticoid receptor antagonist, the mineralocorticoid antagonist altered the birds' reactivity to non‐specific aspects of the training task. These results suggest that the two types of intracellular corticosteroid receptors could be mediating different aspects of the information processing and storage involved in avoidance learning. In addition, this study points out that passive avoidance learning in the chick could be a good model to investigate the biochemical mechanisms involved in corticosteroid actions on learning‐induced neural plasticity
Host Serotonin Axons Innervate Intrastriatal Ventral Mesencephalic Grafts After Implantation in Newborn Rats
Authors: Mounir Abderrahmane , Chkirate Mariem , Vallée Annie , Pierret Philippe , Geffard Michel , Doucet Guy
Published: April 2006

This study investigated the potential of immature and adult serotonin (5HT) neurons for axonal growth into intrastriatal grafts of ventral mesencephalic tissue. Implantation of dissociated fetal (embryonic days 14–15) ventral mesencephalic tissue was carried out in immature [postnatal days (P) 5–14] and adult rat neostriatum. The brains were processed 2–6 months later for dopamine and 5‐HT immunocytochemistry. A few grafts implanted into adult and P7 recipients contained small numbers of cotransplanted 5HT cell bodies. These also displayed a rich network of 5‐HT axons, even in adult rats prelesioned with 5,7‐dihydroxytryptamine, indicating the graft origin of these axons. All other grafts were totally devoid of 5‐HT cell bodies. After implantation in adults, such grafts contained rare 5‐HT axons. In contrast, in P5‐P7 recipients, they displayed many 5‐HT fibres, which were uniformly distributed. Such was no longer the case after implantation in P14 recipients, which showed minimal 5HT innervation, as in adult recipients. Processing of naïve rat brain at different ages for 5‐HT immunocytochemistry showed that 5‐HT axons were still clearly less numerous in the neostriatum at P21 than in adults, whereas in the substantia nigra the 5‐HT innervation developed more rapidly and was comparable, at P21, to that of adults. It was concluded that 5‐HT axons are able to grow into ventral mesencephalic grafts, but mainly at the fetal stage and with decreasing capacity after birth. Since 5‐HT axons are still normally growing in the developing striatum beyond P21, it appears that their inability to innervate mesencephalic grafts after P14 is not the result of a developmental decrease in growth capacity. Rather, the better temporal correlation with the maturation of the 5‐HT innervation in the substantia nigra suggests that this inability reflects an ontogenic change in the affinity of these axons for nigral tissue.
Ca2+/Calmodulin‐dependent Nitric Oxide Synthase in Apis mellifera and Drosophila melanogaster
Authors: Müller Uli
Published: April 2006

NADPH diaphorase (NADPHd) is a marker enzyme for nitric oxide (NO)‐producing cells in vertebrates. This paper investigates the relationship between NADPHd and the NO‐producing enzyme NO synthase (NOS) in neuronal tissue of Apis and Drosophila, two insects used for studying learning. First, the NOS and the NADPHd in both species were characterized biochemically. The fixation‐insensitive NADPHd activity, which accounts for the staining in NADPHd histochemistry, co‐purifies with the insect Ca2+/calmodulin‐dependent NOS. Formation of NO from l‐arginine depends on NADPH, and half‐maximal stimulation is observed with 0.3 μM Ca2+. NOS is competitively inhibited by methyll‐arginine and nitro‐l‐arginine, with Kiof 1.7 and 1.9 μM, respectively. The co‐purification and the competitive inhibition of NOS by the NADPHd substrate, nitro blue tetrazolium (NBT), are proof that in insects the enzyme responsible for fixation‐insensitive NADPHd activity is nitric oxide synthase. Second, the NOS activity was quantified in distinct neuropiles and the NO‐producing neuropiles were visualized using NADPHd histochemistry. In both species the highest NOS activity is found in the chemosensory neuropiles of the antenna1 lobes, intermediate activity in the neuropiles of the central brain and by far the lowest NOS activity in the visual neuropiles. Although in both species the Kenyon cell somata of the mushroom bodies show no detectable staining, the neuropiles of the mushroom bodies of Drosophila and Apis show a distinct staining. The staining pattern of NOS in both species is different to that of all known neurotransmitters.
Opposing Roles for Dopamine D2 and D3 Receptors on Neurotensin mRNA Expression in Nucleus Accumbens
Authors: Diaz J. , Lévesque D. , Griffon N. , Lammers C.H. , Martres M.‐P. , Sokoloff P. , Schwartz J.‐C.
Published: April 2006

Using in situ hybridization histochemistry in rat nucleus accumbens, we show that the dopamine D3 receptor mRNA is expressed in the ventromedial part of the shell subdivision, where its gross distribution matches that of neurotensin mRNA. In addition, hybridization studies at the cellullar level show that a large fraction of the neurotensin neurons co‐express the D3 receptor mRNA in this restricted area. In contrast, the dopamine D2 receptor mRNA is expressed mainly in the core and marginally in the shell, at the level of the cone. In rats treated by haloperidol and sulpiride, two D2‐like receptor antagonists, but not by SCH 23390, a D1‐like receptor antagonist, proneurotensin mRNA was increased in the D2 receptor mRNA‐rich areas but decreased in the D3 receptor mRNA‐rich areas. This suggests that the D2 and D3 receptors control neurotensin mRNA expression negatively and positively, respectively.
Electrotonic Clusters in the Dendritic Arborization of Abducens Motoneurons of the Rat
Authors: Korogod S. , Bras H. , Sarana V. N. , Gogan P. , Tyc‐Dumont S.
Published: April 2006

Following reconstruction with high spatial resolution of the 3‐D geometry of the dendritic arborizations of two abducens motoneurons, we simulated the distribution of electrotonic voltage over the whole dendritic tree. Here, we demonstrate that the complex stochastic electrotonic structure of both motoneurons can be reduced to a statistically significant small set of well discriminated clusters. These clusters are formed by dendritic branches belonging to different dendrites of the neuron but with similar electrotonic properties. A cluster analysis was performed to estimate quantitatively the partition of the branches between the dendritic clusters. The contents of the clusters were analysed in relation to their stability under different values of specific membrane resistivity (Rm), to their remoteness from the soma and their location in 3‐D space. The cluster analysis was executed in a 2‐D parameter space in which each dendritic branch was described by the mean electrotonic voltage and gradient. The number of clusters was found to be four for each motoneuron when computations were made with Rm= 3 kΩ.cm2. An analysis of the cluster composition under different Rm revealed that each cluster contained invariant and variant branches. Mapping the clusters upon the dendritic geometry of the arborizations allowed us to describe the cluster distribution in terms of the 3‐D space domain, the 2‐D path distance domain and the total surface area of the tree. As the cluster behaviour reflects both the geometry and the changes in the neuronal electrotonic structure, we conclude that cluster analysis provides a tool to handle the functional complexity of the arborizations without losing relevant information. In terms of synaptic activities, the stable dendritic branches in each cluster may process the synaptic inputs in a similar manner. The high percentage of stable branches indicates that geometry is a major factor of stability for the electrotonic clusters. Conversely, the variant branches introduce the conditions for mechanisms of functional postsynaptic plasticity.
Distribution of Nicotinic Receptors in the Human Hippocampus and Thalamus
Authors: Rubboli F. , Court J. A. , Sala C. , Morris C. , Chini B. , Perry E. , Clementi F.
Published: April 2006

Neuronal nicotinic acetylcholine receptors consist of different subunits, α and β, with different subtype arrangement corresponding to distinct pharmacological and functional properties. The expression of α3, α7 and β2 mRNA in the human brain was studied by in situ hybridization and compared to [3H]nicotine, [3H]cytisine and [125l]α‐bungarotoxin binding in contiguous sections. The β2 probe showed a strong hybridization signal in the granular layer of the dentate gyrus and in the CA2/CA3 region of the hippocampus and in the insular cortex, and a signal of lower intensity in the subicular complex and entorhinal cortex. The α3 probe showed strong hybridization in the dorsomedial, lateral posterior, ventroposteromedial and reticular nuclei of the thalamus, and a weak signal in the hippocampal region and in the entorhinal, insular and cingular cortex. The amount of α7 mRNA was high at the level of the dentate granular layer and the CA2/CA3 region of the hippocampus, in the caudate nucleus and in the pulvinar and ventroposterolateral nuclei of the thalamus. [3H]Nicotine and [3H]cytisine binding appeared to be identical in anatomical distribution and relative intensity. It was high in the thalamic nuclei, the putamen and in the hippocampal formation in the subicular complex and the stratum lacunosum moleculare. The level of [125l]α‐bungarotoxin binding was particularly high in the hippocampus and in the pyramidal cells of the CA1 region, but was relatively low in the subicular complex. Our data indicate that in the human brain nicotinic receptor subtypes have discrete distributions, which are in part different from those of other species.