bluuebunny/crossref_metadata_2025 huggingface dataset:
Eye position encoding in the macaque posterior parietal cortex
Authors: Bremmer  , Pouget  , Hoffmann K. ‐P.
Published: March 2003

In two previous studies, we had demonstrated the influence of eye position on neuronal discharges in the middle temporal area, medial superior temporal area, lateral intraparietal area and area 7A of the awake monkey ( Bremmer et al. 1997a , b). Eye position effects also have been found in visual cortical areas V3A and V6 and even in the premotor cortex and the supplementary eye field. These effects are generally discussed in light of a coordinate transformation of visual signals into a non‐retinocentric frame of reference. Neural network studies dealing with the eye position effect succeeded in constructing such non‐retinocentric representations by using model neurones whose response characteristics resembled those of ‘real’ neurones. However, to our knowledge, response properties of real neurones never acted as input into these neural networks. In the present study, we thus investigated whether, theoretically, eye position could be estimated from the population discharge of the (previously) recorded neurones and, if so, we intended to develop an encoding algorithm for the position of the eyes in the orbit. The optimal linear estimator proved the capability of the ensemble activity for determining correctly eye position. We then developed the so‐called subpopulation encoding of eye position. This algorithm is based on the partition of the ensemble of neurones into two pairs of subpopulations. Eye position is represented by the differences of activity levels within each pair of subpopulations. Considering this result, encoding of the location of an object relative to the head could easily be accomplished by combining eye position information with the intrinsic knowledge about the retinal location of a visual stimulus. Taken together, these results show that throughout the monkey’s visual cortical system information is available which can be used in a fairly simple manner in order to generate a non‐retinocentric representation of visual information.
Adaptation in patterns of c‐fos expression in the brain associated with exposure to either single or repeated social stress in male rats
Authors: Martinez Manuela , Phillips Peter J. , Herbert Joe
Published: March 2003

Intraspecific confrontation between male rats represents a biologically relevant form of social stress. C‐fos expression has been used to map the pattern of neural activation following either a single (acute) or repeated (10 times) exposure of an intruder male to a larger male in the latter’s home cage. These conditions induce high levels of aggressive interaction.

Sixty minutes after a single defeat, there was intense c‐fos expression (quantified using image analysis) in restricted areas of the basal forebrain (including lateral septum, bed nucleus of stria terminalis, lateral preoptic area, lateral hypothalamic area, paraventricular nucleus, and medial and central amygdala) as well as in the autonomic and monoaminergic nuclei of the brainstem (central grey, dorsal and median raphe, locus coeruleus and nucleus of the solitary tract). After the tenth defeat, this pattern was modified despite persistently high levels of aggression. Some areas in the forebrain (bed nucleus of stria terminalis, paraventricular nucleus and medial amygdala) continued to express increased c‐fos; others (the septum, lateral hypothalamic area, lateral preoptic area and central amygdala) no longer expressed c‐fos. The brainstem response was equally varied: the central grey and the raphe nuclei continued to respond after repeated defeat, whereas the solitary nucleus and locus coeruleus did not. On the other hand, there was no change in the behaviour of intruder rats after repeated defeat.

This study shows the pattern of adaptation at a cellular level in the basal forebrain and brainstem to repeated defeat. As in our previous studies of repeated restraint, modulation in the expression of c‐fos following repeated stress is highly regionally specific, suggesting that differential neural processing is involved in adaptation to social stress.
Functional diversity of synaptic AMPA/KA receptors from rat as revealed by subtype‐specific antagonists
Authors: Weigand Erik , Keller Bernhard U.
Published: March 2003

Subtype‐specific pharmacological compounds represent important tools to identify the molecular components of synaptically activated glutamate receptors in central neurones. Here, we utilized a collection of subtype‐specific antagonists and modulators to investigate the functional profile of glutamate receptors in identified synapses in thin slices of the cerebellum, hippocampus and brain stem. During whole‐cell patch‐clamp recordings α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate/kainate (AMPA/KA) receptor‐mediated synaptic currents (EPSCs) in cerebellar Purkinje cells were (i) prolonged by 100 μm cyclothiazide, (ii) not significantly changed after preincubation in 10 μm concanavalin A, (iii) not affected by 1 μm Evans Blue or polyamine toxin analogue N‐(4‐hydroxyphenylpropanolyl)‐spermine (NHPPS), but (iv) significantly reduced by high (≥ 100 μm) concentrations of Evans Blue. These pharmacological properties were distinct from those observed in hippocampal granule cells and brain stem interneurones and markedly different from those of recombinant glutamate receptor channels GluR1–GluR6 previously investigated in heterologous expression systems.
Incorporation of mouse neural progenitors transplanted into the rat embryonic forebrain is developmentally regulated and dependent on regional and adhesive properties
Authors: Olsson Martin , Bjerregaard Kristoffer , Winkler Christian , Björklund Monte Gates anders , Campbell Kenneth
Published: March 2003

During development, telencephalic neural progenitors acquire positional specification and give rise to distinct structures such as the striatum and cortex. Here, we examine, in vivo, the influence of developmental stage, cell‐surface molecules and regional differences along the dorso‐ventral and antero‐posterior axes on the selective incorporation of neural progenitors derived from different regions of the developing brain, utilizing a cross‐species in utero transplantation paradigm. Striatal progenitors derived from the embryonic day (E) 12–14 mouse lateral ganglionic eminence (LGE) were observed consistently to incorporate into the developing striatum as early as 24–48 h following intraventricular injection into the E15–17 rat host. By removing cell‐surface molecules from the LGE progenitors, the pattern of incorporation was remarkably different with no preferential striatal incorporation. Cortical progenitors with intact cell‐surface molecules, by contrast, displayed little telencephalic (including striatal) incorporation as compared with precursors from the LGE. However, both progenitors from cortex and LGE incorporated widely into diencephalic and mesencephalic structures. The capacity for integration of precursors derived from the LGE and cortex gradually decreased during development of the host and was minimal in the postnatal day (P) 1 host. Unlike the telencephalic precursors, the vast majority of progenitors derived from the midbrain and cerebellar primordium (with cell‐surface molecules intact) incorporated into diencephalic and midbrain nuclei with only a few cells observed in the telencephalon. These results demonstrate that incorporation of neural progenitors across the ventricular wall in the embryonic host is strictly developmentally regulated, dependent on their position along the antero‐posterior axes and in the case of progenitors from the LGE is mediated by cell‐surface molecules expressed on the transplanted cells.
Long‐term protection of the rat nigrostriatal dopaminergic system by glial cell line‐derived neurotrophic factor against 6‐hydroxydopamine in vivo
Authors: Sullivan  , Opacka‐Juffry  , Blunt
Published: March 2003

Glial cell‐line‐derived neurotrophic factor (GDNF) has been shown to enhance the survival of dopaminergic neurones both in vitro and in vivo, and to protect the rodent dopaminergic system from neurotoxic damage. However, most previous studies have only examined the short‐term protective effects of GDNF. We have investigated the long‐term effects of GDNF on a 6‐hydroxydopamine (6‐OHDA)‐induced lesion of the rat medial forebrain bundle (MFB), which results in complete and irreversible destruction of the nigrostriatal pathway, and is a robust model of Parkinson’s disease.

GDNF was administered ipsilaterally above the substantia nigra and into the lateral ventricle immediately before a unilateral 6‐OHDA injection into the MFB. The effects of GDNF were examined in vivo by behavioural testing and positron emission tomography (PET) at weekly intervals, for 12 weeks. GDNF prevented the development of amphetamine‐induced rotations at all time‐points. PET studies, using [11C]‐RTI‐121 as a tracer for the dopamine transporter, indicated that GDNF prevented 6‐OHDA‐induced reduction of dopamine reuptake sites in the ipsilateral striatum. Post‐mortem neurochemical analysis at 13 weeks after surgery found that GDNF significantly inhibited 6‐OHDA‐induced loss of dopamine, 3,4‐dihydroxyphenylacetic acid and homovanillic acid in the ipsilateral striatum. Immunocytochemistry showed that GDNF reduced 6‐OHDA‐induced loss of tyrosine hydroxylase‐positive neurones in both the substantia nigra pars compacta and ventral tegmental area. We have shown that a single treatment with GDNF can confer long‐term protective effects against a 6‐OHDA lesion, which suggests that this factor may be useful for the treatment of Parkinson’s disease.
Possible involvement of gradients in guidance of receptor cell axons towards their target position on the olfactory bulb
Authors: Gierer Alfred
Published: March 2003

There is increasing evidence for directional guidance of growing axons by molecular gradients in target tissues. Aside from biochemical studies on gradients and their role, the capability of axons to approach their target position from different aspects of a two‐dimensional field is itself an indication for guidance by gradients. According to this criterion, such guidance is expected to be involved not only in map‐formation in the visual system but also in targeting of receptor cell axons in the olfactory bulb. In this paper, physico‐chemical concepts of visual mapping are adapted to olfactory targeting. In both cases there must be sophisticated processing of graded cues in the growing tip of the axon for growth cone navigation. In visual map formation, a target position is determined by influences of cues depending on the position of axonal origin; in olfactory targeting, however, these influences are expected to be based on properties of the receptor‐cell‐specific molecules (possibly including the receptor molecule itself), as well as by gene regulation affecting the levels of expression. According to this concept, the main role of molecules expressed in a receptor‐cell‐type specific manner is not matching specific counterparts on the target tissue, but instead quantitative modulation of growth cone steering for sensing the direction towards the target position.
Increased lesion‐induced sprouting of corticospinal fibres in the myelin‐free rat spinal cord
Authors: Vanek Patrik , Thallmair Michaela , Schwab Martin E. , Kapfhammer Josef P.
Published: March 2003

Myelin contains potent inhibitors of neurite growth which have been implicated in the failure of long‐distance regeneration of nerve fibres within the CNS. These myelin‐associated neurite growth inhibitors may also be involved in the stabilization of neural connections by suppressing sprouting and fibre growth. After lesions of the CNS in neonatal animals, extensive rearrangements of the remaining fibre systems have been observed. In the rat, this plasticity of neuronal connections is severely restricted following the first few weeks of postnatal life, coincident with the progression of myelination of the nervous system. A well‐studied example of postnatal plasticity is the sprouting of one corticospinal tract (CST) into the denervated half of the spinal cord after unilateral motor cortex or pyramidal lesions. In the hamster and rat, significant CST sprouting is restricted to the first 10 postnatal days. Here we show that very extensive sprouting of corticospinal fibres occurs after deafferentations as late as P21 if myelination is prevented by neonatal X‐irradiation in the rat lumbar spinal cord. Sprouted fibres from the intact CST cross the midline and develop large terminal arbors in the denervated spinal cord, suggesting the establishment of synaptic connections. Our results suggest that myelin and its associated neurite growth inhibitors play an important role in the termination of neurite growth permissive periods during postnatal CNS development. Corticospinal sprouting subsequent to lesions early in life, i.e. in the absence of myelin‐associated neurite growth inhibitors may explain the frequent occurrence of mirror movements in patients with hemiplegic cerebral palsy.
Attenuation of the seizure‐induced expression of BDNF mRNA in adult rat brain by an inhibitor of calcium/calmodulin‐dependent protein kinases
Authors: Murray Karl D. , Hayes Valerie Y. , Gall Christine M. , Isackson Paul J.
Published: March 2003

We have examined the potential involvement of calcium/calmodulin‐dependent protein kinases in the regulation of brain‐derived neurotrophic factor mRNA in vivo following kainic acid (kainate)‐induced seizure activity by in situ hybridization. KN‐62, a specific inhibitor of calcium/calmodulin‐dependent protein kinase type II and IV, blocked the characteristic induction of brain‐derived neurotrophic factor mRNA seen following seizure activity. This blockade was specific to calcium/calmodulin‐dependent protein kinase type II and IV as inhibitors of both protein kinase C and cAMP‐dependent protein kinase had no effect. Inhibition of brain‐derived neurotrophic factor mRNA increases varied between brain regions; an almost complete inhibition was seen throughout cortical regions, whereas only partial inhibitory effects were noted within hippocampus. A similar inhibition of increased c‐fos mRNA was observed throughout cortical, hippocampal and diencephalic regions. The two predominant brain‐derived neurotrophic factor transcripts induced by kainate, containing exons I or III, were differentially affected by KN‐62. The cortical induction of exon I was blocked by KN‐62, whereas exon III was not, providing additional evidence for the differential regulation of individual brain‐derived neurotrophic factor transcripts and demonstrating that inhibition of brain‐derived neurotrophic factor induction was not due to general blockade of seizure activity throughout the neocortex. These data implicate calcium/calmodulin‐dependent protein kinase type II or IV in the regulation of brain‐derived neurotrophic factor mRNA in vivo and suggest regionally specific mechanisms occur throughout the brain.
Origin and terminal distribution of the trigeminal projections to the inferior and superior colliculi in the lesser hedgehog tenrec
Authors: Künzle Heinz
Published: March 2003

The trigemino‐tectal projections were investigated with anterograde and retrograde tracing techniques in the Madagascan lesser hedgehog tenrec, Echinops telfairi. There were prominent contralateral projections to the inferior colliculus (CoI) and the superior colliculus (CoS), each showing its own characteristic pattern of terminations. While the projections to the CoI were confined consistently to a circumscribed region in its ventrolateral, external portion, the projections from particularly the rostral trigeminal subdivision to the CoS were distributed inhomogenously across almost the entire rostro‐caudal and mediolateral extents. Comparing these data with the spino‐tectal projections published previously, it demonstrates that the somatotopic organization of ascending tectal afferents is more distinct in the CoI than in the CoS.

There were roughly twice as many trigeminal neurones projecting to the CoS than to the CoI. This difference might be due to the fact that the cells projecting to CoS were distributed extensively across the trigeminal nuclear complex (peak densities in the principal and interpolar subdivisions), while the neurones projecting to the CoI were largely confined to the interpolar and caudal trigeminal subdivisions. The latter cells were located adjacent to the spinal trigeminal tract; the neurones projecting to the CoS occupied preferentially the ventral trigeminal regions at rostral levels, while from the interpolar subdivision caudalward the labelled cells shifted dorsolaterally.

In comparison to other mammals the trigeminal projection to the tenrec’s CoI is unique. There is evidence for such a projection in other species too, but it is poorly documented, presumably due to technical reasons.
Preprodynorphin mRNA‐expressing neurones in the rat parabrachial nucleus: subnuclear localization, hypothalamic projections and colocalization with noxious‐evoked fos‐like immunoreactivity
Authors: Hermanson Ola , Telkov Miroslav , Geijer Thomas , Hallbeck Martin , Blomqvist Anders
Published: March 2003

The dorsal lateral subnucleus of the rat pontine parabrachial nucleus is a major target for ascending nociceptive information from the spinal cord. With in situ hybridization histochemistry, using a radiolabelled cRNA probe, we demonstrate that neurones in and near the dorsal lateral subnucleus express preprodynorphin mRNA. The cRNA probe was constructed from a PCR product amplified from rat genomic DNA. Sequencing of the PCR product revealed that it corresponded to the sequence 466–1101 of the rat preprodynorphin gene exon 4.

Tract tracing experiments, using injection of cholera toxin subunit B into the hypothalamic median preoptic nucleus, showed a retrograde labelling pattern of neurones in the parabrachial nucleus that was almost identical to that of the preprodynorphin mRNA expressing neurones. Double‐labelling, combining immunohistochemical detection of tracer and in situ hybridization, revealed that the retrogradely labelled neurones expressed preprodynorphin mRNA. A similar double‐labelling, combining in situ hybridization with immunohistochemical detection of noxious‐evoked fos following formalin injection into one hindpaw of awake animals, showed that almost all fos‐immunoreactive neurones in the dorsal lateral parabrachial subnucleus also expressed preprodynorphin mRNA. Quantitative analysis suggested that the evoked fos immunoreactivity was accompanied by an increased preprodynorphin mRNA expression.

The findings provide evidence that neurones in the dorsal lateral subnucleus produce dynorphin and project to the median preoptic nucleus, and that noxious stimulation in awake animals synaptically activates the dynorphinergic neurones in this subnucleus. These observations are consistent with the idea of a functional and chemical heterogeneity among different parabrachial subnuclei that serves to produce specific homeostatic responses to stimuli that changes the physiological status of the organism, including tissue damage.
Dominant GABAA receptor/Cl– channel kinetics correlate with the relative expressions of α2, α3, α5 and β3 subunits in embryonic rat neurones
Authors: Serafini  , Maric  , Maric  , Ma  , Fritschy  , Zhang  , Barker
Published: March 2003

The embryonic appearance of GABAergic cells and signals in the rat nervous system coincides with the appearance of transcripts encoding some but not all of the subunits forming GABAA receptor/Cl– channels. Quantitative in situ hybridization studies reveal higher variabilities in α2 and α3 subunit transcripts relative to others examined (α5, β2, β3 and γ2) in six spinal and supraspinal regions. Immunocytochemistry of cells dissociated from the embryonic CNS shows that α2 and α3 subunits are detectable in differentiating neurones. FACS analyses of dissociated cells immunostained with α2‐ or α3‐ antibodies reveal immunopositive subpopulations of variable size in each region. Whole‐cell recordings of acutely adherent neurones show that GABA activates Cl– currents whose fluctuations characteristically vary depending on a neurone’s region of origin. Spectral analyses indicate a predominance of the low frequency (< 5 Hz) components, which vary regionally. Regression analyses reveal that (i) channel properties correlate with subunit transcript levels and (ii) dominant channel kinetics correlate with α2 and α3 subunit transcripts indexed as a ratio and with coexpressions of α5 and β3. The correlations strongly suggest that α3 subunits in embryonic neurones are expressed in native receptor/channel complexes with slower kinetics than those containing α2 without α3 subunits. Thus, GABAA receptor/Cl– channels in these embryonic neurones may be encoded by the six transcripts (α2, α3, α5, and β2, β3, and γ2) with proportions of α2, α3, α5, and β3 subunits critical in determining their dominant kinetics.
Distribution of GABA receptor ρ subunit transcripts in the rat brain
Authors: Wegelius Katri , Pasternack Michael , Hiltunen Jukka O. , Rivera Claudio , Kaila Kai , Saarma Mart , Reeben Mati
Published: March 2003

The γ‐aminobutyric acid (GABA) receptor ρ subunits recently cloned from rat and human retina are thought to form GABA receptor channels belonging to a pharmacologically distinct receptor class, termed GABAC. In this work we have examined the distribution of ρ1, ρ2 and ρ3 subunits, and found expression of all three transcripts in several regions of the rat nervous system.

In situ hybridization revealed expression of ρ2 in the adult rat retina and some other parts of the visual pathways. A high local ρ2 expression was seen in the superficial grey layer of the superior colliculus, and in the dorsal lateral geniculate nucleus. Expression was also detected in the 6th layer of visual cortex and in the CA1 pyramidal cell layer of hippocampus. With reverse transcriptase–polymerase chain reaction, expression of ρ1 was mainly seen in the adult rat retina and dorsal root ganglia, as well as, at a significantly lower level, in the superior colliculus, hippocampus, brain stem, thalamus, postnatal day 8 (P8) superior colliculus and P8 hippocampus. Expression pattern of ρ3 mRNA was clearly different from that of ρ1 and ρ2, being strongest in the hippocampus, and significantly lower in the retina, dorsal root ganglia and cortex. No ρ3 expression was observed in adult or P8 superior colliculus or in P8 hippocampus.

The present results clearly demonstrate that expression of GABA receptor ρ subunits is not restricted to the retina, but significant expression can also be detected in many other brain regions, especially in those belonging to the visual pathways. The expression pattern of the ρ subunits may be helpful in solving the functional significance of the receptors formed from these subunits.
The rhythmicity of cells of the medial septum/diagonal band of Broca in the awake freely moving rat: relationships with behaviour and hippocampal theta
Authors: King C. , Recce M. , O’Keefe J.
Published: March 2003

Chronic extracellular recordings were obtained from cells of the medial septum and diagonal band of Broca in rats performing a simple behavioural task. The cells were found to display a variety of bursting patterns phase‐locked to hippocampal theta rhythm to a greater or lesser degree. Among phase‐locked cells, no systematic distribution in preferential phase could be found, and these cells were shown to maintain their preferential phase for extended periods. Cells were classified into those which showed signs of a broadening of the repolarization phase of their action potential (‘inflected’: putative cholinergic) and those without (‘non‐inflected’: putative GABAergic). Non‐inflected cells tended to fire rhythmic bursts while inflected cells mostly fired in an irregular fashion, although still significantly phase‐locked to hippocampal theta. In neither population did the phase‐locked cells show any coherent distribution of their preferential phase. Sixty‐five per cent of the rhythmically bursting cells showed a significant correlation between the interburst frequency and the animal’s running speed. Five cells displayed rhythmic activity only when the rat ran in a specific direction. These results have implications for models of septohippocampal function and the effects of variable septal rhythmicity on the production of hippocampal theta rhythm.
Footshock stress but not contextual fear conditioning induces long‐term enhancement of auditory‐evoked potentials in the basolateral amygdala of the freely behaving rat
Authors: Garcia René , Paquereau Joël , Vouimba Rose Marie , Jaffard Robert
Published: March 2003

In this study, rats were bilaterally implanted with electrodes in the amygdala for chronic recording. Auditory click stimulation evoked in the basolateral nucleus a field potential characterized by three positive components: P1, P2 and P3 (peak latencies around: 10, 20 and 30 ms, respectively) which were each followed by three negative components: N1, N2 and N3 (peak latencies around: 13, 30 and 50 ms, respectively). Animals were divided into three groups (context‐same, context‐different and control). Following footshock administration, animals were either re‐exposed to the same conditioning chamber (context‐same group) or placed in a different context (context‐different group) for electrophysiological and behavioural (evaluation of freezing response) recordings. The two early positive‐negative complexes (P1‐N1 and P2‐N2) increased in amplitude from 2 min to 24 h following footshock in both context‐same and context‐different groups. No significant difference was observed between these two groups. The demonstration of significantly larger freezing responses in context‐same subjects on exposure to the aversive conditioned environment indicated that this similarity of effects was not due to lack of conditioning of context under the experimental conditions chosen. We conclude that footshock stress produces general long‐lasting changes in amygdala auditory field potentials that are not significantly affected by contextual fear conditioning.
Neuronal expression of inducible nitric oxide synthase after oxygen and glucose deprivation in rat forebrain slices
Authors: Moro M.A. , De Alba J. , Leza J.C. , Lorenzo P. , Fernández A.P. , Bentura M.L. , Boscá L. , Rodrigo J. , Lizasoain I.
Published: March 2003

Nitric oxide (NO) overproduction has been postulated to contribute significantly to ischaemia‐reperfusion neurotoxicity. Inducible or type II NO synthase (iNOS) synthesizes NO in large quantities for long periods of time. Therefore we investigated the expression and localization of iNOS after oxygen and glucose deprivation in rat forebrain slices. In this experimental model, calcium‐independent NOS activity reached a maximum 180 min after the end of a 20 min oxygen–glucose deprivation period. During the same period of time, the calcium‐independent activity was absent in control forebrain slices. To test whether this calcium‐independent NOS activity was due to the expression of iNOS, the effects of the addition of dexamethasone, cycloheximide and pyrrolidine dithiocarbamate were determined. All of them inhibited the induction of the calcium‐independent NOS activity measured in the rat forebrain slices after oxygen and glucose deprivation. Furthermore, oxygen and glucose deprivation caused the expression of the gene encoding iNOS in rat forebrain slices, as assessed by the detection of iNOS message and protein in these samples. A sixfold increase in the iNOS mRNA levels was observed at 180 min and the time‐course of the expression of iNOS mRNA was in agreement with the temporal profile of iNOS enzymatic activity. Immunohistochemistry analysis revealed that iNOS was highly expressed in neurones, astrocytes and microglial cells. These results demonstrate for the first time that iNOS is expressed in neurones after oxygen and glucose deprivation, and that this expression occurs in short periods of time. These findings suggest that NO can play an important pathogenic role in the tissue damage that occurs after cerebral ischaemia.
Demarcation of prosencephalic regions by CD15‐positive radial glia
Authors: Mai J.K. , Andressen C. , Ashwell K.W.S.
Published: March 2003

A subpopulation of radial glial cells has been identified in the mouse prosencephalon during the second half of embryonic development. This subpopulation, specified by the putative cell adhesion molecule CD15 (Lex, FAL), is arranged in a segmented pattern within the telencephalon and diencephalon. Glial processes, spanning the prosencephalic wall, first appear at E10.5 and remain clearly visible until E19, when staining of discrete nuclei begins to appear. Registration of the correspondence between ventricular and pial surfaces, however, is still possible due to the persistence of individual CD15‐positive fibres. These can be traced even when the initial simple linear (radial) orientation between ventricular and pial surfaces becomes complicated and distorted. After birth, CD15 immunoreactivity is distributed in a mosaic pattern in the forebrain. Because radial glial cells provide a scaffolding system for postmitotic neurones, the pattern of CD15‐positive fibres in the embryonic prosencephalon may also demarcate future discrete regions of the postnatal brain.
Modulation of bradykinin‐induced mechanical hyperalgesia in the rat by activity in abdominal vagal afferents
Authors: Khasar Sachia G. , Miao Frederick J. ‐P. , Jänig Wilfrid , Levine Jon D.
Published: March 2003

Bradykinin‐induced plasma extravasation and mechanical hyperalgesia are sympathetic‐dependent components of inflammation. Noxious stimulation has been found to inhibit bradykinin‐induced plasma extravasation by activating the hypothalamo‐pituitary‐adrenal axis. The sensitivity of this nociceptive‐neuroendocrine feedback control of inflammation is modulated by activity in subdiaphragmatic vagal afferents. In the present study, we tested the hypothesis that activity in the subdiaphragmatic vagus also modifies bradykinin‐induced mechanical hyperalgesia in the rat, using the Randall–Selitto method.

Following subdiaphragmatic vagotomy, the baseline paw‐withdrawal threshold to mechanical stimulation decreased and bradykinin‐induced mechanical hyperalgesia was enhanced. Mechanical hyperalgesia produced by prostaglandin E2, a direct‐acting hyperalgesic agent, was not significantly affected by vagotomy. The effect of subdiaphragmatic vagotomy on bradykinin‐induced hyperalgesia, but not on baseline paw‐withdrawal threshold, was mimicked by coeliac branch vagotomy.

Indomethacin blocked the hyperalgesia in normal rats, but not in vagotomized rats, suggesting that bradykinin‐induced hyperalgesia in normal rats is mediated by prostaglandins, whose role was unexpectedly diminished after vagotomy.

Bradykinin‐induced hyperalgesia in normal rats was abolished by lumbar sympathectomy but not by sympathetic decentralization (cutting the preganglionic axons). In rats that were both vagotomized and sympathectomized, hyperalgesia induced by low‐dose bradykinin was no longer present.

These results demonstrate that vagotomy induces a decrease in baseline mechanical paw‐withdrawal threshold and an enhancement of bradykinin‐induced mechanical hyperalgesia and suggest that these phenomena are generated by actions in peripheral tissues.
Enhanced neurotransmitter release is associated with reduction of neuronal branching in a Drosophila mutant overexpressing frequenin
Authors: Angaut‐Petit D. , Toth P. , Rogero O. , Faille L. , Tejedor F.J. , Ferrús A.
Published: March 2003

Frequenin is a Drosophila Ca2+ binding protein whose overexpression causes a chronic facilitation of transmitter release at the larval neuromuscular junction and multiple firing of action potentials. These functional abnormalities are similar to those found in other hyperexcitable mutants (Shaker, ether‐a‐gogo, Hyperkinetic) which, in turn, exhibit increased branching at the motor nerve endings. We report here that mutants which overexpress frequenin have motor nerve terminals with reduced number and length of branches as well as number of synaptic boutons. Similar defects are observed in transgenic flies which have additional copies of the frequenin gene indicating that the phenotype can be adscribed to the overexpression of the protein. The ultrastructure of boutons, however, appears indistinguishable from wild type. In addition, we show here that frequenin overexpression leads also to a down regulation of Shaker proteins expression. The contrast between the observations in frequenin and the other hyperexcitable mutants indicates that nerve terminal morphology and enhanced transmitter release do not have a direct causal relationship.
Suppression of kindling epileptogenesis in rats by intrahippocampal cholinergic grafts
Authors: Ferencz I. , Kokaia M. , Elmér E. , Keep M. , Kokaia Z. , Lindvall O.
Published: March 2003

Selective immunolesioning of the basal forebrain cholinergic system by 192 IgG‐saporin, which leads to a dramatic loss of the cholinergic innervation in cortical and hippocampal regions, facilitates the development of hippocampal kindling in rats. The aim of the present study was to explore whether grafted cholinergic neurones are able to reverse the lesion‐induced increase of seizure susceptibility. Intraventricular 192 IgG‐saporin was administered to rats which 3 weeks later were implanted with rat embryonic, acetylcholine‐rich septal‐diagonal band tissue (‘cholinergic grafts’) or cortical tissue/vehicle (‘sham grafts’) bilaterally into the hippocampal formation. After 3 months, the grafted animals as well as non‐lesioned control rats were subjected to daily hippocampal kindling stimulations. In the animals with cholinergic grafts, which had reinnervated the hippocampus and dentate gyrus bilaterally, there was a marked suppression of the development of seizures as compared with the hyperexcitable, sham‐grafted rats. This effect was significantly correlated to the density of the graft‐derived cholinergic innervation of the host hippocampal formation. The kindling rate in the rats with cholinergic grafts was similar to that in non‐lesioned controls. These results provide further evidence that the intrinsic basal forebrain cholinergic system dampens kindling epileptogenesis and demonstrate that this function can be exerted also by grafted cholinergic neurones.
Stimulation of 5‐HT1A receptors in the dorsal raphe reverses the impairment of spatial learning caused by intrahippocampal scopolamine in rats
Authors: Carli Mirjana , Bonalumi Pierenrico , Samanin Rosario
Published: March 2003

This study investigated the effect of stimulating 5‐HT1A receptors in the dorsal raphe on the impairment of learning caused by 4 μg/μL scopolamine injected in the CA1 region of the dorsal hippocampus in rats performing a two‐platform spatial discrimination task. At 1 (but not 0.2) μg/0.5 μL administered in the dorsal raphe on each acquisition training day 5 min before bilateral intrahippocampal injection of 4 μg/μL scopolamine, 8‐hydroxy‐2‐ (di‐n‐propylamino) tetralin (8‐OH‐DPAT), a 5‐HT1A receptor agonist, had no effect on choice accuracy and latency or errors of omission but completely antagonized the impairment of choice accuracy by intrahippocampal scopolamine. Administered into the dorsal raphe at 0.2 and 1 μg/0.5 μL, WAY 100635, a 5‐HT1A receptor antagonist, had no effect on rats’ performance or on the impairment caused by intrahippocampal scopolamine but dose‐dependently antagonized the effect of 1 μg/0.5 μL 8‐OH‐DPAT on the scopolamine‐induced deficit. The results show that stimulation of presynaptic 5‐HT1A receptors in the dorsal raphe reverses the deficit caused by intrahippocampal scopolamine, probably by facilitating the transfer of facilitatory information from the entorhinal cortex to the hippocampus. Together with a previous study showing that blockade of postsynaptic hippocampal 5‐HT1A receptors antagonized the effect of intrahippocampal scopolamine in the two‐platform spatial discrimination task (
Carli et al. 1995b
), the results suggest that drugs with presynaptic stimulatory and postsynaptic blocking actions on 5‐HT1A receptors, such as partial agonists at these receptors, may be useful in the symptomatic treatment of human memory disturbances associated with loss of cholinergic innervation to the hippocampus.
Reduced adenosine uptake accelerates ischaemic block of population spikes in hippocampal slices from streptozotocin‐treated diabetic rats
Authors: Cassar Martin , Jones Martyn G. , Szatkowski Marek
Published: March 2003

We have used rats with streptozotocin‐induced diabetes to investigate the effects of hyperglycaemia‐mediated impaired nucleoside uptake on the actions of endogenous adenosine in hippocampal slices. In control tissue under conditions of anoxia and aglycaemia the rise in the extracellular adenosine concentration resulted in complete inhibition of synaptic activity in about 2 min. In slices from previously hyperglycaemic rats the inhibition of synaptically mediated responses occurred significantly faster, although this change could be prevented by insulin treatment. Application of the selective adenosine A1 receptor antagonist [8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX)] prevented the anoxia/aglycaemia‐mediated inhibition and, furthermore, abolished the differences in the electrophysiological responses between control and diabetic tissue. The effects of impaired nucleoside uptake could be mimicked in control slices by applying the nucleoside uptake blocker hydroxynitrobenzylthioinosine (HNBTI). This had the effect of speeding up the rate of anoxia/aglycaemia‐induced synaptic inhibition in control tissue to that seen in diabetic tissue. However, such treatment had no effect on the responses in diabetic tissue as expected if the HNBTI‐sensitive uptake process was already inhibited by the chronic hyperglycaemia.

The impairment of nucleoside uptake by chronic hyperglycaemia results in the potentiation of the modulatory actions of endogenous adenosine in the central nervous system. Such an alteration in adenosine function may be important in explaining behavioural and pathological changes associated with diabetes mellitus.
Functional GABAA receptors on human glioma cells
Authors: Labrakakis Charalampos , Patt Stephan , Hartmann Jana , Kettenmann Helmut
Published: March 2003

Glioma cells in acute slices and in primary culture, and glioma‐derived human cell lines were screened for the presence of functional GABAA receptors. Currents were measured in whole‐cell voltage clamp in response to γ‐aminobutyric acid (GABA). While cells from the most malignant glioma, the glioblastoma multiforme, did not respond to GABA, an inward current (under our experimental conditions with high Cl− concentration in the pipette) was induced in gliomas of lower grades, namely in 71% of oligodendroglioma cells and in 62% of the astrocytoma cells. Glioma cell lines did not express functional GABAA receptors, irrespective of the malignancy of the tumour they originate from. The currents elicited by application of GABA were due to activation of GABAA receptors; the specific agonist muscimol mimicked the response, the antagonists bicuculline and picrotoxin blocked the GABA‐activated current and the benzodiazepine receptor agonist flunitrazepam augmented the GABA‐induced current and the benzodiazepine inverse agonist DMCM decreased the GABA current. Cells were heterogeneous with respect to the direction of the current flow as tested in gramicidin perforated patches: in some cells GABA hyperpolarized the membrane, while in the majority it triggered a depolarization. Moreover, GABA triggered an increase in [Ca2+]i in the majority of the tumour cells due to the activation of Ca2+ channels. Our results suggest a link between the expression of GABA receptors and the growth of glioma cells as the disappearance of functional GABAA receptors parallels unlimited growth typical for malignant tumours and immortal cell lines.
Corneal innervation and sensitivity to noxious stimuli in trkA knockout mice
Authors: De Castro Fernando , Silos‐Santiago Inmaculada , De Armentia Mikel López , Barbacid Mariano , Belmonte Carlos
Published: March 2003

Most primary sensory neurones depend on neurotrophins for survival. Mutant mice in which TrkA, the high‐affinity receptor for nerve growth factor (NGF), has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli. The cornea of the eye is innervated by trigeminal neurones that are activated by noxious mechanical, thermal and chemical stimuli. In the human cornea, these stimuli evoke only sensations of pain. We have analysed the innervation pattern and the response to noxious stimulation of the cornea of trkA (–/–) mutant mice. Corneal nerves were stained with the gold chloride impregnation method. Corneal sensitivity to noxious stimuli was assessed by counting blinking movements evoked by von Frey hairs, topical application of saline at different temperatures and application of acetic acid and capsaicin at different concentrations. In the cornea of trkA (–/–) mutant animals, we observed a drastic reduction in the number of nerve trunks and branches in the corneal stroma. Furthermore, quantitative analysis of the number of thin nerve terminals revealed a marked decrease in the corneal epithelium of trkA (–/–) mice when compared to those present in wild type and trkA (+/–) animals. The blinking response of trkA (–/–) mice to mechanical, thermal and chemical noxious stimuli was also significantly reduced. These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (–/–) mutant mice. However, a small portion of corneal sensory neurones survive in these mice suggesting that they may be NGF independent. On the basis of our results, we propose that these surviving cells are polymodal nociceptive neurones, sensitive to mechanical stimulation, noxious heat and acid.
Block by picrotoxin of a GABAergic chloride channel expressed on crayfish muscle after axotomy
Authors: Adelsberger Helmuth , Brunswieck Sönke , Dudel Josef
Published: March 2003

Outside‐out patches containing a γ‐aminobutyric acid (GABA)‐activated chloride channel expressed after axotomy on crayfish deep extensor abdominal muscle were excised. GABA and the blocker picrotoxin (PTX) were applied to the patches using a liquid filament switch to study the effects of picrotoxin on the GABA‐elicited currents. Coapplication of GABA and PTX resulted in a reduction of the current amplitude compared with that elicited by the same GABA concentration alone. This reduction of the amplitude was dependent on both the GABA and PTX concentrations. The rise time of the current decreased after coapplication of GABA and PTX. Evaluation of the single channel currents and off‐currents in the presence of GABA and PTX showed a dramatic shortening of the burst duration of the channel. The open time distributions were not altered, whereas in the closed time distributions a new closed time was apparent in presence of PTX. Preincubation with PTX prior to the GABA pulse resulted in an increase of the rise time. This effect was dependent on the PTX concentration only. Possible mechanisms are discussed to explain the effects of PTX and are implemented into the existing molecular reaction scheme of the channel.
Effect of heparin‐binding growth‐associated molecule (HB‐GAM) on synaptic transmission and early LTP in rat hippocampal slices
Authors: Lauri  , Rauvala  , Kaila  , Taira
Published: March 2003

Heparin‐binding growth‐associated molecule (HB‐GAM) is an 18‐kDa developmentally regulated protein, which promotes neurite outgrowth, axonal guidance and synaptogenesis through interaction with cell‐surface heparan‐sulphate proteoglycans. We have studied the effect of HB‐GAM on synaptic transmission and long‐term potentiation (LTP) in the area CA1 of rat hippocampal slices, where HB‐GAM mRNA is expressed in an activity‐dependent manner. Injection of recombinant HB‐GAM into the dendritic area inhibited tetanus‐induced LTP without affecting baseline synaptic responses or the N‐methyl‐d‐aspartate (NMDA)‐receptor mediated transmission. HB‐GAM did not depotentiate tetanus‐induced LTP or prevent heterosynaptic LTP induced by application of tetraethylammonium (TEA), indicating that the effect was limited to early, synapse‐specific stages of LTP induction. These results suggest that HB‐GAM is involved in the regulation of synaptic plasticity in hippocampus.
Visuo‐motor transformations for arm reaching
Authors: Lacquaniti  , Caminiti
Published: March 2003

Visuomanual co‐ordination requires the merging of ocular and arm information in a common frame of reference. Here we consider behavioural evidence in humans for the use of a viewer‐centred frame in the specification of end point positions of reaching. We then review anatomical and neurophysiological data in the non‐human primate that indicate a prominent role of the parietal cortex in the process of multisensory fusion that leads to egocentric representations of space. Finally, we discuss the functional anatomy of the human parietal cortex in visuomanual co‐ordination as revealed by neuroimaging.
Somatostatin receptor subtypes sst1 and sst2 elicit opposite effects on the response to glutamate of mouse hypothalamic neurones: an electrophysiological and single cell RT‐PCR study
Authors: Lanneau Christophe , Viollet Cécile , Faivre‐Bauman Annie , Loudes Catherine , Kordon Claude , Epelbaum Jacques , Gardette Robert
Published: March 2003

We have previously shown that somatostatin can either enhance or decrease AMPA/kainate receptor‐mediated responses to glutamate in mouse‐dissociated hypothalamic neurones grown in vitro. To investigate whether this effect is due to differential activation of somatostatin (SRIF) receptor subtypes, we compared modulation of the response to glutamate by SRIF with that induced by CH‐275 and octreotide, two selective agonists of sst1 and sst2/sst5 receptors, respectively. Somatostatin either significantly decreased (49%) or increased (30%) peak currents induced by glutamate, and was ineffective in the remaining cells. Only the decreased response was obtained with octreotide, whereas only increased responses were elicited by CH‐275 (47 and 35% of the tested cells, respectively). Mean amplitude variations under somatostatin or octreotide on the one hand, and under somatostatin or CH‐275 on the other hand, were equivalent. Pertussis toxin pretreatment significantly decreased the number of cells inhibited by somatostatin or octreotide, but had no effect on the frequency of neurones showing increased sensitivity to glutamate during somatostatin or CH‐275 application. About half of the neurones tested by single cell reverse transcriptase polymerase chain reaction (RT‐PCR) expressed only one sst receptor (sst1 in 26% and sst2 in 22% of studied cells). Out of the remaining neurones, 34% displayed neither sst1 nor sst2 mRNAs, whereas 18% showed a simultaneous expression of both mRNA subtypes. Expression of sst1 or sst2 mRNA subtypes matched totally with the effects of somatostatin on sensitivity to glutamate in 79% of the neurones processed for PCR after recordings. These data show that pertussis toxin‐insensitive activation of the sst1 receptor subtype mediates somatostatin‐induced increase in sensitivity to glutamate, whereas decrease in the response to glutamate is linked to pertussis toxin‐sensitive activation of the sst2 receptor subtype.