bluuebunny/crossref_metadata_2025 huggingface dataset:
Transection of Corticostriatal Afferents Reduces Amphetamine‐ and Apomorphine‐induced Striatal Fos Expression and Turning Behaviour in Unilaterally 6‐Hydroxydopamine‐lesioned Rats
Authors: Cenci M. A. , Björklund A.
Published: April 2006

Corticofugal fibres from the prefrontal, prelimibic and anterior sensorimotor cortices were transected by a wide coronal knife‐cut through the forceps minor. The cut was performed on the dopamine‐depleted side of unilaterally 6‐hydroxydopamine‐lesioned rats, or on either the right or the left side of intact rats. Sham‐lesioned controls received a superficial cortical cut at the same level. Seven days after surgery, apomorphine (0.25 mg/kg s.c.) was administered to 6‐hydroxydopamine‐lesioned animals and D‐amphetamine (5 mg/kg i.p.) was administered to the non‐dopamine‐denervated ones. Two hours later, the animals were perfusion‐fixed for the immunohistochemical detection of the nuclear protein Fos. A computerized image analysis technique was used to quantify, bilaterally, striatal Fos expression in 11 areas of the striatum. The frontocortical transection reduced both apomorphine‐ and amphetamine‐induced Fos expression by 33 – 66% within the ipsilateral caudate‐putamen. The effect was observed throughout the rostral portion of the striatal complex, where the lesioned cortical fibres terminate most densely. A separate batch of unilaterally 6‐hydroxydopamine‐lesioned rats was used to test the effect of frontocortical transection on amphetamine‐and apomorphine‐induced turning behaviour. Two groups of rats, showing similar rates of contralateral turning (7 – 8 turns/min) in response to apomorphine (0.25 mg/kg s.c.), were subjected to either a complete frontocortical transection or a sham lesion on the dopamine‐denervated side. An additional two groups, showing comparable rates of ipsilateral turning (15 turns/min) in response to amphetamine (5 mg/kg i. p.), received similar lesions, but now on the side ipsilateral to the intact dopaminergic innervation. The frontocortical transection reduced both apomorphine‐ and amphetamine‐induced turning by, on average, 40%, while the sham lesion had no effect. The present findings suggest that the full expression of dopamine‐receptor‐induced Fos activation and turning behaviour depends on an intact glutamatergic corticostriatal input.
C‐fos mRNA is Spontaneously Induced in the Rat Brain During the Activity Period of the Circadian Cycle
Authors: Grassi‐Zucconi G. , Menegazzi M. , De Prati A. Carcereri , Bassetti A. , Montagnese P. , Mandile P. , Cosi C. , Bentivoglio M.
Published: April 2006

The basal expression of the proto‐oncogene c‐fos was studied by Northern blot analysis in different regions of the rat brain during 24 h. A striking spontaneous oscillation of c‐fos mRNA expression was detected in animals kept in basal conditions with a 12 h light/12 h dark cycle. In these animals c‐fos mRNA was just detectable during the rest hours (morning through afternoon), and was high during the activity hours (night). The periodicity of this oscillation persisted and became free‐running when the animals were exposed for 6 consecutive days to constant light or darkness. It was thus demonstrated that the fluctuation of c‐fos expression is circadian and is not created by the light‐dark cycle, but the latter exerts a synchronizing effect. The oscillation of c‐fos mRNA was modified by manipulations of the rest‐activity cycle. In particular, the fluctuation observed in basal conditions was inverted, keeping the animals awake during the rest hours (diurnal) and allowing them to sleep in the activity period (nocturnal). These data indicated a close relationship between the oscillation of c‐fos expression and the rest‐activity cycle. Finally, electroencephalographic (EEG) monitoring was performed under behavioural control for 3 h before the animals were killed. These experiments confirmed that, irrespective of the time of day, the EEG pattern typical of a state of sleep (including both slow waves and paradoxical sleep) was associated with low or undetectable c‐fos levels, whereas the protracted EEG desynchronization corresponding to wakefulness was associated with high c‐fos expression. Altogether these results indicate that c‐fos mRNA undergoes during the circadian cycle spontaneous oscillations related to the activation of genomic expression subserving the behavioural and electrical correlates of wakefulness. On the other hand, the behavioural and electrical correlates of sleep are associated with low c‐fos expression.
Long‐term Depression Requires Nitric Oxide and Guanosine 3′:5’Cyclic Monophosphate Production in Rat Cerebellar Purkinje Cells
Authors: Daniel H. , Hemart N. , Jaillard D. , Crepel F.
Published: April 2006

In patch‐clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG‐methyl‐l‐arginine consistently prevents the induction of long‐term depression (LTD) of parallel fibre‐mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8‐bromoguanosine 3′:5’cyclic monophosphate is able to reproduce an LTD‐like phenomenon. LTD of parallel fibre‐mediated EPSPs also occurs when nitric oxide donors or guanosine 3′:5’cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.
Distribution of Gephyrin Transcripts in the Adult and Developing Rat Brain
Authors: Kirsch J. , Malosio M.‐L. , Wolters I. , Betz H.
Published: April 2006

The peripheral membrane protein gephyrin copurifies with the inhibitory glycine receptor of mammalian spinal cord. It binds with high affinity to polymerized tubulin and has been implicated in the anchoring of the glycine receptor to cytoskeletal elements. Recently, cDNA cloning has identified variants of the gephyrin mRNA, which originate from alternative splicing of four exonic regions (cassettes 1 – 4). In this study, the expression patterns of gephyrin splice variants were determined in the adult and developing rat brain byin situhybridization with synthetic oligonucleotide probes. Gephyrin transcripts were detected throughout the brain and spinal cord, with mRNAs containing cassette 2 (C2 transcripts) being predominant in adult animals. C3 and C4 transcripts were seen in cerebellar granule cells and in the dentate gyrus, whereas a C1 probe did not produce detectable hybridization signals. During development, C2 and C3 mRNAs were found in most brain regions. Generally, the spatial and temporal distribution of gephyrin transcripts is similar to that of the glycine receptor β subunit mRNA reported previously.
Changes in DNA Synthesis Rate in the Schwann Cell Lineage In Vivo Are Correlated With the Precursor – Schwann Cell Transition and Myelination
Authors: Stewart Helen J. S. , Morgan Louise , Jessen Kristjan R. , Mirsky Rhona
Published: April 2006

During the development of the rat sciatic nerve extensive proliferation of glial cells occurs, and there is a very substantial rearrangement of the cytoarchitecture as axons and Schwann cells assume relationships which lead to the formation of the myelinated and unmyelinated axons characteristic of adult nerve. The maturation of Schwann cells from Schwann cell precursors and the matching of Schwann cell numbers to axons is an important part of this process. We have therefore studied the proliferation of Schwann cell precursors and Schwann cells during the development of the rat sciatic nerve from embryonic day 14 to postnatal day 28 by combining bromodeoxyuridine injections of rats with double‐label immunohistochemical techniques. The results reveal that DNA synthesis occurs in both Schwann cell precursors and Schwann cells throughout early nerve development. The labelling index is already substantial at embryonic day 14, but from embryonic day 17, when essentially all the glial cells have converted from precursor to Schwann cell phenotype, it rises sharply, peaking between embryonic day 19 and 20 before declining precipitously in the early postnatal period. This rapid decline in DNA synthesis coincides with the appearance of the myelin protein Po, and in individual cells DNA synthesis is incompatible with the expression of Po protein. Non‐myelin‐forming Schwann cells, which mature later in development, continue to synthesize DNA until at least postnatal day 15, but by day 28 essentially all Schwann cells in the nerve are quiescent.
Sprouting and Regeneration of Lesioned Corticospinal Tract Fibres in the Adult Rat Spinal Cord
Authors: Schnell L. , Schwab M. E.
Published: April 2006

We have studied the effects of tissue transplants and antibodies (IN‐1) against the myelin‐associated neurite growth inhibitory proteins on sprouting and regeneration of the rat corticospinal tract (CST). Transplantation of embryonic spinal cord tissue into bilateral transection lesions of the lower thoracic spinal cord in young adult rats resulted in a marked increase of the sprouting of the lesioned CST. This sprouting effect was probably elicited by soluble factors released from the transplants, and was enhanced by the IN‐1 antibodies. The retraction of lesioned CST fibres normally observed with prolonged survival times was also reduced by the presence of transplants. In spite of these growth‐promoting effects of the transplants, the regenerative elongation of CST sprouts into the caudal spinal cord was dependent upon the neutralization of the myelin‐associated inhibitory proteins. In the controls (no antibodies or control antibodies) only 27% of the animals showed elongation of CST fibres exceeding the sprouting distance of 0.7 mm. These fibres grew to a maximal length of 1.8 mm (mean±SEM, 1.2±0.1). In contrast, 60% of the IN‐1‐treated, transplant‐containing rats showed elongations of >0.7 mm, and these fibres grew up to 10.1 mm (4.6±0.5). Regenerating fibres crossed the lesion site through remaining tissue bridges. Neither embryonic spinal cord transplants nor a variety of implanted bridge materials could serve as a substrate for the regenerating CST axons.
Two Signal Transduction Mechanisms of Substance P‐induced Depolarization in Locus Coeruleus Neurons
Authors: Koyano K. , Velimirovic B. M. , Grigg J. J. , Nakajima S. , Nakajima Y.
Published: April 2006

Effects of substance P on cultured neurons of the locus coeruleus of the rat were studied using the whole‐cell patch clamp technique. In some cells substance P produced a decrease in a K conductance which showed an inwardly rectifying property. In other cells substance P produced an initial inward current which was accompanied by a conductance increase. The rest of the cells showed responses which were mixtures of the above two responses. The measurement of the reversal potential of the initial inward current after suppressing the voltage‐gated Ca and K conductances suggests that it is caused by an increase in a non‐selective ionic conductance. In cells loaded with 260 μM GTPγS, application of substance P produced an irreversible reduction of the K conductance, while the initial inward current could still be recorded, suggesting that the former is mediated by a G protein, whereas the latter may be activated by a different signal transduction mechanism. The initial inward current was not eliminated by external application of high concentrations of tetrodotoxin, d‐tubocurarine or amiloride. Nor was it affected by the intracellular application of cyclic GMP or cyclic AMP.
Fos Immunoreactivity after Stimulation or Inhibition of Muscarinic Receptors Indicates Anatomical Specificity for Cholinergic Control of Striatal Efferent Neurons and Cortical Neurons in the Rat
Authors: Bernard Véronique , Dumartin Brigitte , Lamy Eliette , Bloch Bertrand
Published: April 2006

Cholinergic neurons play a major role in the control of striatal activity via muscarinic receptors. The action of acetylcholine also appears to be dependent on the striosome – matrix compartmentalization of the striatum. This study was designed to find out whether modification of acetylcholine tone activates neurons in the striatum and forebrain of the rat. We looked for the appearance of immunoreactivity to Fos, a regulatory protein that is thought to convert synaptic signals into changes in gene expression. Pharmacological manipulation of muscarinic receptors was found to induce specific patterns of Fos immunoreactivity in distinct neuronal populations of the forebrain, including the striatum. Oxotremorine, a non‐selective muscarinic agonist, induced Fos immunoreactivity in the striatum with a large predominance in striosomes (mostly in enkephalinergic neurons), in layers 4 and 6 of the cortex, and also in the piriform cortex and septum. The muscarinic agonist pilocarpine had an identical effect in the cortex, but the striosomal prevalence was less clear‐cut than that observed after oxotremorine. Treatment with dopamine‐depleting agents (6‐hydroxydopamine or reserpine) and inhibitors of glutamate and opiate receptor (MK‐801 and naloxone respectively) had no effect on the action of oxotremorine. This suggests that the induction of Fos provoked by oxotremorine does not involve dopamine, glutamate or opiates. Atropine, a non‐specific muscarinic antagonist, also induced Fos immunoreactivity in the striatum but with matrix predominance (mostly in substance P neurons), as well as in the cingulate cortex, and the olfactory tubercle. Scopolamine, a muscarinic antagonist, induced Fos in both striosomal and matrix compartments in the striatum. No Fos immunoreactivity was observed after change in acetylcholine tone in cholinergic or somatostatinergic neurons of the striatum, or in dopaminergic neurons of the substantia nigra. Our results demonstrate that stimulation or inhibition of muscarinic receptors induces Fos activation in striatal efferent neurons with topological (striosome/matrix) and phenotypical (enkephalin/substance P) prevalence and specificity and also in cortical neurons with also topological prevalence. These data suggest that in humans, direct or indirect modifications of the cholinergic neurotransmission induced by pathological states or by drugs may lead to neuronal events in the forebrain triggered by Fos activation.
The Role of Serotonin Receptor Subtypes in the Behavioural Effects of Neuroleptic Drugs. A Paw Test Study in Rats
Authors: Ellenbroek Bart A. , Prinssen Eric P. M. , Cools Alexander R.
Published: April 2006

The present study was designed to evaluate the roles of serotonin 5‐HT1A and 5‐HT2 receptors in the effects of neuroleptic drugs in the paw test. This behavioural test has been shown to model both the antipsychotic efficacy as well as the extrapyramidal side‐effect liability of neuroleptic drugs. Whereas the 5‐HT1A receptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OHDPAT) reduced the effects of the classical neuroleptic haloperidol, it increased the effects of the atypical neuroleptic clozapine. The 5‐HT2 receptor antagonist ketanserin as well as the 5‐HT1C/5‐HT2 receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5‐HT1C/5‐HT2 receptor agonist 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOl) reduced the effects of clozapine. The most important finding, however, was that the behavioural effects of different (putative) neuroleptics (fluphenazine, SCH‐39166, remoxipride, prothipendyl, thioridazine and risperidone) were differentially influenced by both 8‐OHDPAT and DOl, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subclasses of classical and atypical neuroleptics.
Heterogeneity Among Neuroepithelial Cells in the Chick Retina Revealed by Immunostaining with Monoclonal Antibody PM1
Authors: Hernández‐Sánchez Catalina , Frade José M. , de La Rosa Enrique J.
Published: April 2006

Neuroepithelial cells appear as a homogeneous population of cells in the cell cycle that seem to behave as pluripotent neural precursors. The study of the intrinsic heterogeneity and subtle developmental changes among neuroepithelial cells has been hindered by the lack of specific markers. To address that study, a panel of monoclonal antibodies was produced against early developing chick retina. The monoclonal antibody precursor marker 1 (PM1) labels most, if not all, of the early neuroepithelial cells in embryonic day 4 retinal sections. This pattern is transient since the labelling becomes restricted to the peripheral retina as development proceeds and eventually disappears from the neuroepithelial cells. However, apparently in parallel, the differentiating retinal ganglion cells become PM1‐positive. The expression of the PM1 antigen, a 73 × 103Mr protein, as shown by western blotting, also decreases with development. In addition, a chick retina dissociated‐cell culture system, where retinal neuroepithelial cells actively proliferate and undergo differentiation under defined conditions, in combination with monoclonal antibody PM1, allowed us to characterize and quantify the proliferating and differentiating neuroepithelial cells. Interestingly, the fraction of total neuroepithelial cells that are stained with PM1 sharply decreases as retinal development proceeds, in correlation with the staining pattern in sections from matched stages. These data thus reveal that the pluripotent neural precursors in the chick retina already represent an intrinsically heterogeneous population, and that this population changes with development.
Lamellar Organization of Pontocerebellar Neuronal Populations. A Multi‐tracer and 3‐D Computer Reconstruction Study in the Cat
Authors: Nikundiwe Alfeo M. , Bjaalie Jan G. , Brodal Per
Published: April 2006

This study deals with the three‐dimensional arrangement of populations of pontocerebellar cell bodies projecting to the parafloccular complex. The fluorescent tracers rhodamine B isothiocyanate, fluoro‐gold and fast blue were injected in either adjacent or separated cerebellar folia. A set of coordinates (x, y, z) was assigned to each retrogradely labelled cell and the total distribution reconstructed and displayed on a graphics workstation. At a large scale, we found that the majority of the cells of each labelled population (all projecting to the same folium) were confined to a lamella‐shaped tissue volume. Each lamella extended from medial to lateral, and accordingly followed the curving of the pontine grey around the corticospinal and corticobulbar fibre tracts. At a smaller scale, i.e. within each lamellar subspace, the neurons belonging to one labelled population were distributed in aggregates of various shapes. To enable further analysis of the shapes of the intralaminar aggregates, we developed a computer program for unfolding of the lamellae, based on cubic B‐spline approximation. The flattened reconstructions were three‐dimensional polygonal windows, circumscribing the large majority of the labelled cell swarm (usually 70–80% of the total number of labelled cells in one population). The present findings, taken together with previous data on a gradual, rather than disjunctive, shift of pontocerebellar neuronal position in relation to a gradual shift of target region (Bjaalie et al., Anat Rec, 231, 510–523, 1991), suggest that the cerebropontocerebellar system may be organized according to a set of fairly simple topographic rules.
Release of Acetylcholine and Noradrenaline from the Cholinergic and Adrenergic Afferents in Rat Hippocampal CA1, CA3 and Dentate Gyrus Regions
Authors: Milusheva E. , Baranyi M. , Zelles T. , Mike Á. , Vizi E. S.
Published: April 2006

An attempt was made to study the release of acetylcholine (ACh) and noradrenaline and their presynaptic modulation in isolated slice preparations dissected from different subfields of the hippocampus: CA1, CA3 and the dentate gyrus. The slices were perfused and loaded with [3H]choline or with [3H]noradrenaline. The release in response to field stimulation was determined radiochemically and the content of transmitters was assayed by a chemiluminescent method or by HPLC combined with electrochemical detection. After 30 min of loading with [3H]choline there were marked subregional differences in the specific activity of [3H]ACh content. The highest concentration was measured in the dentate gyrus and the lowest in CA3. Evidence was obtained that in all three subfields the cholinergic axon terminals are equipped with inhibitory muscarinic autoreceptors and the noradrenergic terminals with α2‐autoreceptors, as indicated by an increase in transmitter release when the tissue was exposed to selective muscarinic or α2‐adrenoceptor antagonists. In contrast, the cholinergic boutons are not equipped with α2‐adrenoceptors, and noradrenergic terminals do not possess inhibitory muscarinic receptors. It is therefore concluded that while the release of both ACh and noradrenaline is controlled by negative feedback modulation, there is no possibility of establishing a presynaptic inhibitory interaction between the two.
Temporal Structure of a Bimanual Goal‐directed Movement Sequence in Monkeys
Authors: Kazennikov O. , Wicki U. , Corboz M. , Hyland B. , Palmeri A. , Rouiller E. M. , Wiesendanger M.
Published: April 2006

The aim of the present investigation was to assess a bimanual goal‐oriented movement sequence with particular emphasis on its temporal structure. The three monkeys (Macaca fascicularis) used in this study chose the left arm as the leading and more postural arm to reach out and pull back a spring‐loaded drawer containing a food morsel. The right arm followed the left and picked up the food with a precision grip. Video recordings, trajectory recordings of the two index fingers, drawer displacement and the measurements of discrete events of the left and right hand revealed a considerable trial‐by‐trial variability in the temporal and spatial domain. The variability of latencies progressively increased from the initiation of the bimanual sequence to the left‐hand and right‐hand events defining goal achievement. The main result was that, in spite of this variability in each of the two limbs, there was an invariant left‐right goal‐related synchronization. The timing of the goal‐related event pairs covaried and showed high correlation coefficients. Covariation of the two hands resulting in an invariant synchronization was particularly striking when monkeys performed the task without vision, and timing of right and left movement components was delayed with further increase in variability. The results indicate that, in the present bimanual skill, kinaesthetic signals may be sufficient to coordinate the two limbs in a goal‐oriented unitary action in accord with a memorized plan.
trkC‐like Immunoreactivity in the Primate Descending Serotoninergic System
Authors: Arvidsson Ulf , Risling Mårten , Frisén Jonas , Piehl Fredrik , Fried Kaj , Hökfelt Tomas , Cullheim Staffan
Published: April 2006

In the search for substances with a potential role in plastic responses of spinal motoneurons we have studied the distribution of trkC‐like immunoreactivity in the spinal cord of adult monkeys (Macaca fascicularis). The presence of trkC, which is a signal‐transducing receptor for neurotrophin‐3, was detected by the use of indirect immunofluorescence with a rabbit polyclonal antibody raised against a synthetic peptide corresponding to the carboxy‐terminal domain of the mouse trkC‐encoded protein, thus detecting only full‐length signal‐transducing receptors.trkC‐immunoreactive fibres/varicosities could be found at all spinal cord levels and the densest innervation was found in the autonomic intermediolateral and Onuf's nuclei, but somatic motoneuron pools also received a significant contribution of trkC‐immunoreactive fibres. Terminals immunoreactive for trkC were also seen in the dorsal horn. Double‐labelling experiments revealed a high degree of coexistence between trkC‐ and 5‐hydroxytryptamine (serotonin)‐like immunoreactivity in all areas except in the dorsal horn. The results of the present study suggest that neurotrophic signalling with an influence on serotoninergic as well as non‐serotoninergic inputs to the adult monkey spinal cord is at hand.
Blockade of Prefronto‐cortical α1‐Adrenergic Receptors Prevents Locomotor Hyperactivity Induced by Subcortical D‐Amphetamine Injection
Authors: Blanc G. , Trovero F. , Vezina P. , Hervé D. , Godeheu A.‐M. , Glowinski J. , Tassin J.‐P.
Published: April 2006

The stimulation of cortical dopaminergic D1 receptors can counteract the increased locomotor activity evoked by D‐amphetamine application in the nucleus accumbens (Vezina et al., Eur. J. Neurosci., 3, 1001–1007, 1991). Moreover, an α1 antagonist, prazosin, prevents the locomotor hyperactivity induced by electrolytic lesions of the ventral tegmental area (Trovero et al., Neuroscience, 47, 69–76, 1992). Attempts were thus made to see whether blockade of α1‐adrenergic receptors in the rat prefrontal cortex could reduce nucleus accumbens D‐amphetamine‐evoked locomotor activity. Rats implanted chronically and bilaterally with cannulae into the medial prefrontal cortex and the nucleus accumbens were used for this purpose and locomotor activity was monitored in circular corridors. Preliminary experiments indicated that intraperitoneal injection of prazosin (0.06 mg/kg) reduces the locomotor hyperactivity induced by the peripheral administration of D‐amphetamine (0.75 mg/kg). This effect of prazosin was not observed when locomotor hyperactivity was obtained by an intraperitoneal injection of scopolamine (0.8 mg/kg). Bilateral nucleus accumbens injections of D‐amphetamine (4.0 nmol/side) markedly increased locomotor activity, as estimated in a 30 min period. Prior (20 min) bilateral injections of either prazosin or WB‐4101 (0.16 pmol) into the medial prefrontal cortex abolished the nucleus accumbens D‐amphetamine‐evoked response. The recovery of the nucleus accumbens D‐amphetamine‐evoked response was closely dependent on the amount of prazosin used, very prolonged inhibitory effects of the drug being seen with a high amount (>4 days with 160 pmol). In contrast, whatever the amount of WB‐4101 used (0.16–160 pmol), recovery occurred within 3 days. It is suggested that the blockade of cortical d‐adrenergic receptors facilitates locally dopaminergic D1 transmission. This latter effect may counteract the increased locomotor activity induced by the application of D‐amphetamine into the nucleus accumbens.
Increases in Neuronal Bursting Recorded From the Chick Lobus Parolfactorius After Training Are Both Time‐dependent and Memory‐specific
Authors: Gigg John , Patterson Teresa A. , Rose Steven P. R.
Published: April 2006

Day‐old‐chicks can be trained in one trial to avoid a methylanthranilate‐coated bead (methyl‐chicks). The lobus parolfactorius of the chick forebrain is an important structure for memory of this avoidance response. To examine training‐induced electrophysiological changes in this structure, spontaneous neuronal bursting activity was measured from the lobus parolfactorius of anaesthetized, day‐old methyl‐ and water‐chicks (the latter chicks trained to peck at a water‐coated bead) over the period 1 – 10 h post‐test. Bursting was significantly higher in methyl‐chicks over this period. This post‐test increase was time‐dependent: bursting in methyl‐chicks was significantly higher only during the period 4–7 h post‐test. In a second experiment, methyl‐chicks were subjected to brief, subconvulsive electroshock 5 min post‐training. When tested 1 h later about half of these chicks showed recall (avoided the bead) and half were amnesic (pecked the bead). These chicks were anaesthetized and bursting was recorded from the lobus parolfactorius. Chicks that showed recall exhibited a significantly higher level of bursting over the period 1 – 10 h post‐test when compared to chicks that were amnesic. The time course of bursting was similar to that seen in non‐electroshocked methyl‐chicks. These results suggest that passive avoidance training induces a memory‐specific, time‐dependent increase in neuronal activity within the lobus parolfactorius of day‐old chicks. This increase may be directly associated with long‐term consolidation of memory for the task.
Altered Calcitonin Gene‐related Peptide, Substance P and Enkephalin Immunoreactivities and Receptor Binding Sites in the Dorsal Spinal Cord of the Polyarthritic Rat
Authors: Kar S. , Rees R. G. , Quirion R.
Published: April 2006

The dorsal horn of the spinal cord, which forms the locus of first synapses in pain pathways, is an important site of interaction between calcitonin gene‐related peptide (CGRP), substance P and enkephalin—the neuropeptides considered to be especially involved in the regulation of pain perception. Since adjuvant‐induced arthritic rats provide a suitable model for peripheral inflammation and hyperalgesia, the possible alterations of immunoreactive CGRP, substance P and enkephalin as well as the binding sites for [125I]hCGRPα, [125I]substance Plneurokinin‐1, (NK1) and [125I]FK‐33‐824/μ‐opioid receptors were studied in the dorsal horn of the spinal cord receiving projections from the inflamed limbs. In arthritic rats compared to control animals, a bilateral increase in CGRP‐ and substance P‐immunoreactive fibres and the presence of enkephalin‐immunoreactive cell bodies were noted in the dorsal horn of the spinal cord. As for receptors, while a significant decrease in [125I]hCGRPα and [125I]substance P/NK1 binding sites was observed in selective layers, no measurable alteration in [125I]FK‐33‐824/μ‐opioid binding sites was noted in any regions of the arthritic rat dorsal horn compared to the unaffected control rats. Following unilateral section of the peripheral nerve prior to induction of arthritis, CGRP‐ and substance P‐immunoreactive fibres were markedly depleted and no enkephalin‐positive neurons were observed in the ipsilateral dorsal horn. Analysis of receptor binding sites in denervated arthritic rats, however, exhibited differential responses, i.e. a significant increase in [125I]hCGRPα, a marked decrease in [125I]FK‐33‐824/μ‐opioid and apparently no alteration in [125I]substance P/NK1 receptor binding sites were observed in the ipsilateral dorsal horn compared to the intact contralateral side. These results taken together provide anatomical evidence for a concerted role of these peptides in the regulation of adjuvant‐induced hyperalgesia accompanying peripheral inflammation.
Relationship Between Tyrosine Hydroxylase Content and Noradrenergic Cell ‐Reactivity to Piperoxane: an In Vivo Voltammetric Approach in the Rat Locus Coeruleus
Authors: Vachette Cédric , Debure Laure , Rousset Colette , Pujol Jean‐François , Renaud Bernard
Published: April 2006

A previous electrochemical study showed that the increase in the tyrosine hydroxylase (TH) content of the locus coeruleus (LC) produced by RU24722 administration was associated with a relative decrease in the catecholaminergic metabolic reactivity of this nucleus to a hypotensive stimulus. Since α2 receptors participate in the regulation of the activity of both LC neurons and TH, the aim of the present work was to evaluate the possible involvement of the autoinhibition mediated by α2, autoreceptors in the inverse relationship between the reactivity of the LC and its TH content. Our study was divided into two successive steps: (i) the electrochemical measurement of the in vivo metabolic activation of LC cells in response to α2,‐adrenergic receptor blockade, and (ii) the evaluation of the quantity of TH every 100 μm along the caudo‐rostra1 axis in each recorded LC. The capacity of TH protein to be activated was evaluated by the measurement, using differential normal pulse voltammetry, of the in vivo variations of the extracellular 3, 4‐dihydroxyphenylacetic acid concentrations in response to six cumulated doses of the α2,‐antagonist piperoxane. The corresponding dose‐response curves, determined in control‐and RU24722‐treated rats, were expressed as a function of the quantity of TH contained either in the whole recorded LC or in the 100 μm‐wide coronal interval surrounding the recording site. It was established that the slopes of the dose‐response curves were significantly (P < 0.01) and inversely related to the quantity of TH at the level of the recording site. This result suggests that the negative control of the catecholaminergic metabolic reactivity in a restricted area of the LC could be directly or indirectly dependent on the level of expression of TH protein in this particular area.
Further Studies on Motor and Sensory Nerve Regeneration in Mice With Delayed Wallerian Degeneration
Authors: Brown M. C. , Perry V. H. , Hunt S. P. , Lapper S. R.
Published: April 2006

The axons of both peripheral and central neurons in C57BL/Wlds (C57BL/Ola) mice are unique among mammals in degenerating extremely slowly after axotomy. Motor and sensory axons attempting to regenerate are thus confronted with an intact distal nerve stump rather than axon‐and myelin‐free Schwann cell‐filled endoneurial tubes. Surprisingly, however, motor axons in the sciatic nerve innervating the soleus muscle regenerate rapidly, and there is evidence that they may use Schwann cells associated with unmyelinated fibres as a pathway. If this is so, motor axon regeneration might be impaired in C57BL/Wlds mice in the phrenic nerve, which has very few unmyelinated fibres. We found that as long as the myelinated axons in the distal stump of the phrenic nerve remained intact (up to 10 days), regeneration of motor axons did not occur, in spite of vigorous production of sprouts at the crush site. In contrast to motor axons, myelinated sensory axons regenerate very poorly in C57BL/Wlds mice, even in the presence of unmyelinated axons. We showed that this was also due to adverse local conditions confronting nerve sprouts, for the dorsal root ganglion cell bodies responded normally to injury with a rapid induction of Jun protein‐like immunoreactivity and when the saphenous nerve was forced to degenerate more rapidly by multiple crush lesions sensory axons regrew much more successfully. The findings show that motor and sensory axons in C57BL/Wlds mice, although very atypical in the way that they degenerate, are able to regenerate normally but only in an appropriate environment. The results also give support to the view that intact peripheral nerves either fail to encourage or actively inhibit axon growth, and that an unsuitable local environment can prevent regeneration even if the cell body is reacting normally to injury.
Differential Foci and Synaptic Organization of the Principal and Spinal Trigeminal Projections to the Thalamus in the Rat
Authors: Williams Matthew N. , Zahm Daniel S. , Jacquin Mark F.
Published: April 2006

The thalamus is known to receive single‐whisker ‘lemniscal’ inputs from the trigeminal nucleus principalis (Prv) and multiwhisker ‘paralemniscal’ inputs from the spinal trigeminal nucleus (Spv), yet the responses of cells in the thalamic ventroposteromedial nucleus (VPM) are most similar to and contingent upon inputs from PrV. This may reflect a differential termination pattern, density and/or synaptic organization of PrV and SpV projections. This hypothesis was tested in adult rats using anterograde double‐labelling with fluorescent dextrans, horseradish peroxidase (HRP) and choleragenoid, referenced against parvalbumin and calbindin immunoreactivity. The results indicated that Prv's most robust thalamic projection is to the whisker‐related barreloids of VPM. The SpV had robust projections to non‐barreloid thalamic regions, including the VPM ‘shell’ encapsulating the barreloid area, a caudal and ventral region of VPM that lacks barreloids and PrV inputs, the posterior thalamic nucleus, nucleus submedius and zona incerta. Within the barreloid portion of VPM, SpV projections were sparse relative to those from PrV, and most terminal labelling occurred in the peripheral fringes of whisker‐related patches and in inter‐barreloid septae. Thus, PrV and SpV have largely complementary projection foci in the thalamus. Intra‐axonal staining of a small sample of trigeminothalamic axons with whisker or guard hair receptive fields revealed highly localized and somatotopic terminal aggregates in VPM that spanned areas no larger than that of a single barreloid. In the electron microscopic component of this study, HRP transport to the barreloid region of VPM from left SpV and right PrV in the same cases revealed PrV terminals contacting dendrites with a broad range of minor axis diameters (mean ± SD: 1. 51 ± 0. 10 μm). SpV terminals were indistinguishable from those of PrV, but they had a disproportionate number of contacts on narrow dendrites (1. 27 ± 0. 07 μm, P 0. 01). PrV endings were also more likely to contact VPM somata (11. 0 ± 4. 2% of all labelled terminals) than those from SpV (3. 0 ± 1. O%, P 0. 01). Insofar as primary dendrites are thicker than distal dendrites in VPM, these data suggest a differential distribution of PrV and SpV inputs onto VPM cells that may account for their relative efficacies in dictating the responses of VPM cells to whisker stimulation. Multiwhisker receptive fields in VPM may also reflect direct transmission of convergent inputs from PrV.
LGN‐projecting Neurons of the Cat's Pretectum Express Glutamic Acid Decarboxylase mRNA
Authors: Wahle Petra , Stuphorn V. , Schmidt M. , Hoffmann K.‐P.
Published: April 2006

There have been conflicting reports on the chemical nature of the projection of the pretectal nuclei [nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract (NOT DTN complex) and posterior pretectal nucleus] to the lateral geniculate nucleus and inferior olive. There is evidence that the pretecto‐geniculate pathway is inhibitory. However, most attempts to verify the GABAergic nature of the projection neurons have failed. In order to answer this question, we employed a combination of retrograde transport and in situ hybridization. Rhodamine‐labelled latex microspheres were injected into the electrophysiologically identified lateral geniculate nucleus. In addition, fluorescein‐labelled latex microspheres were injected into the inferior olive. Retrograde axonal transport labelled large pretectal neurons. We then applied riboprobes specific for glutamic acid decarboxylase mRNA. We were able to demonstrate glutamic acid decarboxylase mRNA expression in up to 70% of lateral geniculate nucleus‐projecting NOT‐DTN and posterior pretectal nucleus neurons but in none of the pretecto‐olivary projection neurons. The results suggest that the pretecto‐geniculate projection is GABAergic in nature, which would confirm previous electrophysiological and morphological observations. The pretecto‐olivary projection is not GABAergic.
The Effect of Cycloheximide and Ganglioside GM1 on the Viability of Retinotectally Projecting Ganglion Cells Following Ablation of the Superior Colliculus in Neonatal Rats
Authors: Harvey A. R. , Cui Q. , Robertson D.
Published: April 2006

The time‐course and extent of death of retinal ganglion cells (RGCs) following ablation of the superior colliculus (SC) in neonatal Wistar rats has recently been described [Harvey, A. R. and Robertson, D. (1992) J. Comp. Neurol., 325, 83–94]. Normal and pyknotic nuclei of retinotectally projecting ganglion cells were visualized using the fluorescent retrograde tracer diamidino yellow (DY), which had been injected into the SC at P2 (day of birth = P0), 2 days prior to tectal removal. The present report sets out to determine whether cycloheximide, an inhibitor of protein synthesis, or ganglioside GM1 reduced this lesion‐induced RGC death. All surgery was carried out under ether anaesthesia; DY was injected into the left SC at P2 and the injected area was removed at P4. Cycloheximide (20‐500 ng) was injected into the vitreous chamber of the right eye immediately after the lesion and again 11 ‐12 h later. In some rats, cycloheximide administration was delayed until 12 h after the SC ablation. Control rats received SC lesions alone or lesions plus sham eye injections of saline. Different doses of GM1 were applied i.p. or intraocularly. Rats were perfused 24 h after the SC lesion, at the time of peak RGC death. Retinae of lesion only or sham eye injected rats contained ‐11% pyknotic RGCs and the density of normal RGCs was ‐3400/mm2. The rate of pyknosis in cycloheximide treated retinae was reduced to ‐3%. Normal RGC density in these retinae was ∼5500/mm2, similar to that found in retinae of unlesioned animals. Delaying the application of cycloheximide significantly reduced its effectiveness in preventing RGC death. GM1 treatments had no, or only minor, impact on RGC pyknosis 24 h after SC removal. The data are consistent with the proposal that RGC death after neonatal loss of central target sites is an active process that requires protein synthesis. It is therefore possible that, in the developing mammalian visual system, target‐derived neurotrophic factors maintain RGC viability by suppressing some form of endogenous suicide program within the neurons.
Inhibition of Neuronal Activity in the Nucleus of the Optic Tract due to Electrical Stimulation of the Medial Terminal Nucleus in the Rat
Authors: van der Togt Chris , Schmidt Matthias
Published: April 2006

Morphologically, a GABAergic connection between the medial terminal nucleus of the accessory optic system and the nucleus of the optic tract, two primary visual nuclei involved in the optokinetic reflex, has been demonstrated. In this study it was investigated if the medial terminal nucleus forms an inhibitory input to movement direction selective units in the nucleus of the optic tract. Neurons in the nucleus of the optic tract were visually stimulated with moving large random square patterns in their preferred and non‐preferred direction, and their activity was recorded extracellularly. Concomitantly, bipolar electrical stimulation was applied to the medial terminal nucleus and its effect was studied on the visual responses of units in the nucleus of the optic tract. Units in the nucleus of the optic tract were strongly inhibited during electrical stimulation of the medial terminal nucleus. The role of GABA in mediating this inhibition was investigated by applying bicuculline, a GABAA receptor antagonist, iontophoretically to the recorded units in the nucleus of the optic tract. However, although average spike rate levels of units in the nucleus of the optic tract increased with bicuculline, bicuculline did not reduce inhibition invoked by electrical stimulation of the medial terminal nucleus. A possible explanation for this observation is that this inhibition is GABAB receptor mediated.
Distribution of Glutamatergic Receptors and GAD mRNA‐Containing Neurons in the Vestibular Nuclei of Normal and Hemilabyrinthectomized Rats
Authors: de Waele C. , Abitbol M. , Chat M. , Menini C. , Mallet J. , Vidal P. P.
Published: April 2006

Vestibular compensation is an attractive model for investigations of cellular mechanisms underlying post‐lesional plasticity in the adult central nervous system. Immediately after hemilabyrinthectomy, the spontaneous activity in the deafferented second‐order vestibular neurons falls to zero, resulting in a strong asymmetry between the resting discharge of the vestibular complexes on the lesioned and intact sides. This asymmetry most probably causes the static and dynamic vestibular deficits observed in the acute stage. After ∼50 h, the deafferented vestibular neurons recover a quasi‐normal resting activity which is thought to be the key of the compensation of the static vestibular syndromes. However, the molecular mechanisms underlying this recovery are unknown. In this study, we investigate possible changes in the distribution of glutamatergic N‐methyl‐d‐aspartate (NMDA) and glutamate metabotropic receptors and of glutamate decarboxylase 67k (GAD 67k) mRNAs in the deafferented vestibular neurons induced by the labyrinthine lesion. Specific radioactive oligonucleotides were used to probe sections of rat vestibular nuclei according to in situ hybridization methods. Animals were killed at different times (5 h, 3 days and 3 weeks) following the lesion. Signal was detected by means of film or emulsion autoradiography. In the normal animals, several brainstem regions including the medial, lateral, inferior and superior vestibular nuclei were densely labelled by the antisense oligonucleotide NMDAR1 probe. However, the vestibular nuclei were not labelled by the glutamate metabotropic oligonucleotide antisense probe (mGluR 1). The GAD 67k antisense oligonucleotide probe labelled numerous small‐ to medium‐sized central vestibular neurons but not the larger cell bodies in the lateral vestibular nucleus. This agrees with previous studies. In the hemilabyrinthectomized rats, no asymmetry could be detected, at either the autoradiographic or cellular levels, between the two medial vestibular nuclei whatever the probe used and whatever the delay following the lesion. However, for the NMDAR1 probe, the mean density of silver grains in both the deafferented and intact medial vestibular neurons was 20% lower 5 h after the lesion. Three days and 3 weeks later, the intensity of labelling over all cells was the same as in the control group. Further studies are necessary to confirm the relatively weak modification of the NMDAR1 mRNAs expression and to exclude a change of GAD 65 and of other NMDA subunit mRNAs during the vestibular compensation process.
Morphological and Molecular Characterization of the Response of Differentiated PC12 Cells to Calcium Stress
Authors: Michel Patrick P. , Vyas Sheela , Anglade Philippe , Ruberg Merle , Agid Yves
Published: April 2006

The mechanisms that lead ultimately to neuronal death in pathological ageing of the brain remain mostly unknown as in the case of Parkinson's disease where there is a progressive and selective loss of dopaminergic neurons within the substantia nigra. Dopamine‐expressing PC12 cells that were neuronally differentiated by nerve growth factor treatment were chosen as a culture model in which to study some of the changes that may occur during the course of the degenerative process. They were exposed to the calcium ionophore A23187 in order to produce a sustained rise in cytoplasmic calcium, a phenomenon related to various pathological conditions. The degenerative effects of the ionophore were dose‐ and time‐dependent. They were characterized by early fragmentation of the neurites followed ultimately by a loss in cell viability. Biochemical changes, such as a decrease in [3H]dopamine uptake and modulations of the tyrosine hydroxylase gene, were detected before macroscopic evidence of cell suffering (e.g. neurite fragmentation) could be observed. Although an ongoing degenerative process was occurring in cell somata, PC12 cells were able to recover upon ionophore withdrawal. Characteristics of apoptosis such as chromatin condensation and DNA fragmentation were detectable in a small population of dying cells. DNA fragmentation could be prevented by the endonuclease inhibitor aurintricarboxylic acid. New protein synthesis was not required, as cycloheximide failed to prevent degeneration. Taken together, these results suggest that differentiated PC12 cells react to calcium stress through a sequence of regulatory processes which appears to be independent of the apoptotic pathway.