bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential c‐fos expression in the rhinencephalon and striatum after enhanced sleep–wake states in the cat
Authors: Sastre J. P. , Buda C. , Lin J. S. , Jouvet M.
Published: March 2003

In order to delimit the supra‐brainstem structures that are activated during the sleep–waking cycle, we have examined c‐fos immunoreactivity in four groups of polygraphically recorded cats killed after 3 h of prolonged waking (W), slow‐wave sleep (SWS), or paradoxical sleep (PS), following microinjection of muscimol (a γ‐aminobutyric acid, GABA agonist) into the periaqueductal grey matter and adjacent areas [Sastre et al. (1996), Neuroscience, 74, 415–426]. Our results demonstrate that there was a direct relationship between a significant increase in c‐fos labelling and the amount of PS in the laterodorsalis tegmenti in the pons, supramamillary nucleus, septum, hippocampus, gyrus cingulate, amygdala, stria terminalis and the accumbens nuclei. Moreover, in all these structures, the number of Fos‐like immunoreactive neurons in the PS group was significantly higher (three to 30‐fold) than in the SWS and W groups. We suggest that the dense expression of the immediate‐early gene c‐fos in the rhinencephalon and striatum may be considered as a tonic component of PS at the molecular level and that, during PS, the rhinencephalon and striatum are the main targets of an excitatory system originating in the pons.
The serotonin 5‐HT2 receptor–phospholipase C system inhibits the induction of long‐term potentiation in the rat visual cortex
Authors: Edagawa Yoshikuni , Saito Hiroshi , Abe Kazuho
Published: March 2003

The effect of serotonin 5‐HT2 receptor stimulation on long‐term potentiation (LTP) in the primary visual cortex was investigated by using rat brain slices in vitro. Field potentials evoked by stimulation of layer IV were recorded in layer II/III. The 5‐HT2 receptor agonist 1‐(2,5‐dimethyl‐4‐iodophenyl)‐2‐aminopropane (DOI) did not affect baseline synaptic potentials evoked by single‐pulse test stimulation, but significantly inhibited the induction of LTP in a concentration‐dependent manner (0.1–10 μm). The LTP‐inhibiting effect of DOI (10 μm) was blocked by the 5‐HT2,7 receptor antagonist ritanserin (10 μm), but not by the 5‐HT1A receptor antagonist NAN‐190 (10 μm) nor by the 5‐HT3,4 receptor antagonist MDL72222 (10 μm). The inhibitory effect of DOI was also blocked by the phospholipase C inhibitor U73122, but not by its inactive analogue U73343. These results suggest that visual cortex LTP is inhibited by activation of the 5‐HT2 receptor–phospholipase C system. In addition, the LTP‐inhibiting effect of DOI was abolished by the presence of the GABAA receptor antagonist bicuculline (10 μm), suggesting that 5‐HT2 receptor‐mediated inhibition of visual cortex LTP is dependent on GABAergic inhibition.
The distribution of the mRNA and protein products of the melanin‐concentrating hormone (MCH) receptor gene, slc‐1, in the central nervous system of the rat
Authors: Hervieu G. J. , Cluderay J. E. , Harrison D. , Meakin J. , Maycox P. , Nasir S. , Leslie R. A.
Published: March 2003

Melanin‐concentrating hormone (MCH), a 19 amino acid cyclic peptide, is largely expressed in the hypothalamus. It is implicated in the control of general arousal and goal‐orientated behaviours in mammals, and appears to be a key messenger in the regulation of food intake. An understanding of the biological actions of MCH has been so far hampered by the lack of information about its receptor(s) and their location in the brain. We recently identified the orphan G‐protein‐coupled receptor SLC‐1 as a receptor for the neuropeptide MCH. We used in situ hybridization histochemistry and immunohistochemistry to determine the distribution of SLC‐1 mRNA and its protein product in the rat brain and spinal cord. SLC‐1 mRNA and protein were found to be widely and strongly expressed throughout the brain. Immunoreactivity was observed in areas that largely overlapped with regions mapping positive for mRNA. SLC‐1 signals were observed in the cerebral cortex, caudate‐putamen, hippocampal formation, amygdala, hypothalamus and thalamus, as well as in various nuclei of the mesencephalon and rhombencephalon. The distribution of the receptor mRNA and immunolabelling was in good general agreement with the previously reported distribution of MCH itself. Our data are consistent with the known biological effects of MCH in the brain, e.g. modulation of the stress response, sexual behaviour, anxiety, learning, seizure production, grooming and sensory gating, and with a role for SLC‐1 in mediating these physiological actions.
Acetylcholine stimulates cortical precursor cell proliferation in vitro via muscarinic receptor activation and MAP kinase phosphorylation
Authors: Ma Wu , Maric Dragan , Li Bing‐sheng , Hu Qian , Andreadis Joanne D. , Grant Geraldine M. , Liu Qi‐Ying , Shaffer Kara M. , Chang Yoong H. , Zhang Lei , Pancrazio Joseph J. , Pant Harish C. , Stenger David A. , Barker Jeffery L.
Published: March 2003

Increasing evidence has shown that some neurotransmitters act as growth‐regulatory signals during brain development. Here we report a role for the classical neurotransmitter acetylcholine (ACh) to stimulate proliferation of neural stem cells and stem cell‐derived progenitor cells during neural cell lineage progression in vitro. Neuroepithelial cells in the ventricular zone of the embryonic rat cortex were found to express the m2 subtype of the muscarinic receptor. Neural precursor cells dissociated from the embryonic rat cortical neuroepithelium were expanded in culture with basic fibroblast growth factor (bFGF). reverse transcriptase‐polymerase chain reaction (RT‐PCR) revealed the presence of m2, m3 and m4 muscarinic receptor subtype transcripts, while immunocytochemistry demonstrated m2 protein. ACh and carbachol induced an increase in cytosolic Ca2+ and membrane currents in proliferating (BrdU+) cells, both of which were abolished by atropine. Exposure of bFGF‐deprived precursor cells to muscarinic agonists not only increased both cell number and DNA synthesis, but also enhanced differentiation of neurons. These effects were blocked by atropine, indicating the involvement of muscarinic ACh receptors. The growth‐stimulating effects were also antagonized by a panel of inhibitors of second messengers, including 1,2‐bis‐(O‐aminophenoxy)‐ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA‐AM) to chelate cytosolic Ca2+, EGTA to complex extracellular Ca2+, pertussis toxin, which uncouples certain G‐proteins, the protein kinase C inhibitor H7 and the mitogen‐activated protein kinase (MAPK) inhibitor PD98059. Muscarinic agonists activated MAPK, which was significantly inhibited by atropine and the same panel of inhibitors. Thus, muscarinic receptors expressed by neural precursors transduce a growth‐regulatory signal during neurogenesis via pathways involving pertussis toxin‐sensitive G‐proteins, Ca2+ signalling, protein kinase C activation, MAPK phosphorylation and DNA synthesis.
Interleukin‐6 inhibits neurotransmitter release and the spread of excitation in the rat cerebral cortex
Authors: D'arcangelo Giovanna , Tancredi Virginia , Onofri Franco , D'antuono Margherita , Giovedì Silvia , Benfenati Fabio
Published: March 2003

Cytokines are extracellular mediators that have been reported to affect neurotransmitter release and synaptic plasticity phenomena when applied in vitro. Most of these effects occur rapidly after the application of the cytokines and are presumably mediated through the activation of protein phosphorylation processes. While many cytokines have an inflammatory action, interleukin‐6 (IL‐6) has been found to have a neuroprotective effect against ischaemia lesions and glutamate excitotoxicity, and to increase neuronal survival in a variety of experimental conditions. In this paper, the functional effects of IL‐6 on the spread of excitation visualized by dark‐field/infrared videomicroscopy in rat cortical slices and on glutamate release from cortical synaptosomes were analysed and correlated with the activation of the STAT3, mitogen‐activated protein kinase ERK (MAPK/ERK) and stress‐activated protein kinase/cJun NH2‐terminal kinase (SAPK/JNK) pathways. We have found that IL‐6 depresses the spread of excitation and evoked glutamate release in the cerebral cortex, and that these effects are accompanied by a stimulation of STAT3 tyrosine phosphorylation, an inhibition of MAPK/ERK activity, a decreased phosphorylation of the presynaptic MAPK/ERK substrate synapsin I and no detectable effects on SAPK/JNK. The effects of IL‐6 were effectively counteracted by treatment of the cortical slices with the tyrosine kinase inhibitor lavendustin A. The inhibitory effects of IL‐6 on glutamate release and on the spread of excitation in the rat cerebral cortex indicate that the protective effect of IL‐6 on neuronal survival could be mediated by a downregulation of neuronal activity, release of excitatory neurotransmitters and MAPK/ERK activity.
Dynorphins directly inhibit neuronal nicotinic acetylcholine receptors in PC12 cells
Authors: Itoh Hideki , Andoh Tomio , Watanabe Itaru , Sasaki Tosio , Kamiya Yoshinori , Okumura Fukuichiro
Published: March 2003

The authors have previously reported that dynorphin A (1–17), an endogenous kappa opioid agonist, inhibits the current mediated through neuronal nicotinic acetylcholine receptors (nAChRs) without the involvement of opioid receptors or G‐proteins. We have further characterized this action to elucidate the mechanisms. The nicotine‐induced current was studied in PC12 cells using patch‐clamp techniques. In the whole‐cell configuration, four kinds of dynorphins with different lengths, dynorphin A (1–17) (1–13) (2–13) and (1–8), similarly inhibited the nicotine‐induced inward current at 1 μm and accelerated the current decay. The inhibition by dynorphin A (1–17) was not antagonized by the increasing concentrations of nicotine. The current–voltage relationship revealed that dynorphin's inhibition was voltage independent at the membrane potentials from −30 to −70 mV. The inhibition was not affected by pretreatment with pertussis toxin (PTX) or inclusion of staurosporine into the pipette solution. The inhibitory effect of dynorphin A (1–17) was well preserved in the outside‐out patch configuration. Analysis of the nicotine‐induced noise and single‐channel kinetics revealed that dynorphin A(1–17) reduced open time without changing the amplitude of the unitary current. We found that the inhibitory effect on neuronal nAChRs is shared by all four dynorphins studied. The inhibition appears to be non‐competitive and voltage independent. The outside‐out recording together with other experiments indicated that a major part of this inhibition is not mediated through cytoplasmic messengers, but based on the direct action of dynorphins on neuronal nAChRs leading to the reduction of open time.
Synaptotagmin I and IV define distinct populations of neuronal transport vesicles
Authors: Berton Frédérique , Cornet Véronique , Iborra Cécile , Garrido Juan , Dargent Bénédicte , Fukuda Mitsunori , Seagar Michael , Marquèze Béatrice
Published: March 2003

Mammalian synaptotagmins constitute a multigene family of at least 11 membrane proteins. We have characterized synaptotagmin IV using antibodies directed against the C2A domain of the protein. Antibodies reacted specifically with a protein band that migrated as a 41–44 kDa doublet. Synaptotagmin IV expression was regulated throughout development. A strong decrease in the amount detected by Western blotting occurred between postnatal day 5 and adulthood, in agreement with studies on the expression of synaptotagmin IV transcripts. In subcellular fractionation, synaptotagmin IV was not detected in the synaptic vesicle‐enriched fraction. Immunofluorescence microscopy was concordant with this finding. In 6‐day‐old rat cerebellum and cultured hippocampal neurons the subcellular distribution of synaptotagmin IV was clearly different from that of synaptotagmin I. Synaptotagmin IV displayed a punctate non‐polarized distribution on neuronal extensions, whereas synaptotagmin I staining was essentially synaptic. Synaptotagmin IV staining was also observed in the soma in strong perinuclear fluorescent puncta superimposed on that of Golgi/TGN markers. Furthermore, synaptotagmin IV was seen in the proximal part of the growth cone domain and not in the microfilament‐rich region which includes filopodia. Co‐localizations with the adhesion molecules vinculin and zyxin at the proximal part of growth cones were observed. Synaptotagmin IV may thus be involved in the regulation of specific membrane‐trafficking pathways during brain development.
Trk B signalling controls LTP but not LTD expression in the developing rat visual cortex
Authors: Sermasi Edoardo , Margotti Elisa , Cattaneo Antonino , Domenici Luciano
Published: March 2003

Neurotrophins have been suggested to act as liaison molecules between activity‐dependent synaptic plasticity and the establishment of patterns of synaptic connectivity during postnatal developmental in different brain areas, including the visual cortex. In particular, recent studies have shown that Trk B ligands are involved in the formation of the ocular dominance columns during postnatal development. Here, we examined the contribution of endogenous Trk B activation to the regulation of different forms of synaptic plasticity including long‐term potentiation (LTP), long‐term depression (LTD) and LTP after LTD in the developing visual cortex. Rat cortical slices were incubated with a soluble form of Trk B receptor (TrkB IgG) preventing Trk B activation by endogenous ligands. LTP expression was also studied at P23 (postnatal), when the expression of brain‐derived neurotrophic factor (BDNF) reaches a peak and the LTP expression is normally downregulated. The present results demonstrate that Trk B activation is required for the long‐term maintenance, > 30 min, of both LTP and LTP after LTD at P17. At P23, a higher concentration of TrkB IgG was necessary to impair LTP. In contrast, neither amplitude nor duration of LTD were affected by Trk B ligands blockade. Taken together, these results indicate that endogenous Trk B ligands are necessary for the expression of LTP but not LTD at a critical time during postnatal cortical development.
Free radical production correlates with cell death in an in vitro model of epilepsy
Authors: Frantseva Marina V. , Velazquez Jose L. Perez , Hwang Paul A. , Carlen Peter L.
Published: March 2003

Free radical (FR) production, a major step in calcium‐dependent neurodegeneration, has been linked to the generation of epileptiform activity and seizure‐induced cell death. However, direct evidence of FR production in neurons during seizures has never been presented. Using hippocampal cultured slices we demonstrate that FRs are produced in CA3 but not CA1 pyramidal neurons during the rhythmic synchronous activity induced by the GABAA receptor antagonist bicuculline. The production of FRs (measured as changes in the fluorescence emission of dihydrorhodamine 123) was correlated with an increase in the baseline levels of intracellular calcium ([Ca2+]i) estimated by fluo‐3 injected into individual neurons via a patch pipette. [Ca2+]i increased during spike bursting and returned to baseline levels after the burst termination in CA1, but not in CA3, pyramidal neurons where ‘interburst’ calcium concentrations progressively increased. Measurement of cell death, performed with propidium iodide 48 h after a 30‐min exposure to bicuculline, revealed most prominent degeneration of pyramidal neurons in the CA3 pyramidal layer. The FR scavengers vitamin E and glutathione significantly reduced the seizure‐induced neurodegeneration without supressing spontaneous epileptiform activity. These observations indicate that FR overproduction is related to seizure‐induced neuronal death.
Age‐dependent changes in projections from locus coeruleus to hippocampus dentate gyrus and frontal cortex
Authors: Ishida Y. , Shirokawa T. , Miyaishi O. , Komatsu Y. , Isobe K.
Published: March 2003

Age‐dependent changes in noradrenergic innervations of the hippocampal dentate gyrus (DG) and the frontal cortex (FC) have been studied in male F344 rats. The projections from the nucleus locus coeruleus (LC) to DG or FC with advancing age (from 7 to 27 months) in rats have been quantified by electrophysiological and immunohistochemical methods. In the electrophysiological study, we observed that the percentage of LC neurons activated antidromically by electrical stimulation (P‐index) of DG or FC decreased with age. We found that the percentage of LC neurons showing multiple antidromic latencies (M‐index), which suggests axonal branching of individual LC neurons, increased markedly between 15 and 17 months in DG or FC. In DG, the M‐index increased steadily between 15 and 24 months. In contrast, the increased M‐index in FC was maintained until 24 months. The increased M‐index in both targets declined at 27 months. These results suggest that LC neurons give rise to axonal branching following the loss of projections to DG or FC with age. In the immunohistochemical study, the density of dopamine‐β‐hydroxylase‐positive axonal varicosities was measured in molecular, granule cell and polymorphic layers of DG. The density in the polymorphic layer significantly decreased in the earlier stage of ageing (7–19 months), whilst the density in the molecular and granule cell layers decreased in the later stage (27 months). These findings suggested that a layer‐specific decline occurred with age in the noradrenergic axon terminals in DG.
Bilateral blockade of NMDA receptors in anterior thalamus by dizocilpine (MK‐801) injures pyramidal neurons in rat retrosplenial cortex
Authors: Tomitaka Shinichiro , Tomitaka Midori , Tolliver Bryan K. , Sharp Frank R.
Published: March 2003

Non‐competitive N‐methyl‐ d‐aspartate (NMDA) receptor antagonists, ketamine, phencyclidine (PCP) and dizocilpine (MK‐801), produce psychosis in people. In rodents they produce cytoplasmic vacuoles in injured retrosplenial cortical neurons that express HSP70 heat shock protein. This study examined possible circuits and receptors that mediate this neuronal injury. Bilateral, but not unilateral, injection of dizocilpine (5, 10, 15, 20 μg/μL per side) into the anterior thalamus induced HSP70 protein in pyramidal neurons in deep layer III of rat retrosplenial cortex 24 h later. In contrast, bilateral dizocilpine injections (5, 10, 15, 20 μg/μL per side) into the retrosplenial cortex or into the diagonal band of Broca did not induce HSP70. Bilateral injections of muscimol (0.1, 1, 10 μg/μL per side), a GABAA (γ‐aminobutyric acid) agonist, into the anterior thalamus blocked HSP70 induction in the retrosplenial cortex produced by systemic dizocilpine (1 mg/kg). Bilateral thalamic injections of baclofen (0.1, 1, 10 μg/μL per side), a GABAB agonist, were ineffective. Anterograde tracer studies confirmed that neurons in the anterior thalamus project to superficial layer III of the retrosplenial cortex where the dendrites of HSP70‐immunostained neurons in deep layer III reside. Bilateral blockade of NMDA receptors on GABA neurons in the reticular nuclei of the thalamus is proposed to decrease GABA neuronal firing, decrease GABA release and decrease activation of GABAA receptors. This activates thalamic projection neurons that damage retrosplenial cortical neurons presumably via unblocked cortical glutamate α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA) and kainate receptors. The increases of blood flow that occur in the thalamus and retrosplenial cortex of people that have psychosis produced by NMDA antagonists could be related to thalamic excitation of the retrosplenial cortex produced by these drugs.
Repeated long‐term potentiation induces mossy fibre sprouting and changes the sensibility of hippocampal granule cells to subconvulsive doses of pentylenetetrazol
Authors: Hassan Hadir , Pohle Wulf , Rüthrich Heinz , Brödemann Rudolf , Krug Manfred
Published: March 2003

Electrical and chemical kindling induces sprouting of the mossy fibre system and potentiation of evoked field potentials in the dentate gyrus. It has been postulated that such changes may also be induced by repeated induction of long‐term potentiation (LTP) with tetanic stimulation of the perforant pathway. LTP was induced in rats chronically implanted with stimulation electrodes in the ipsilateral and contralateral angular bundles and with a recording electrode in the ipsilateral dorsal dentate gyrus. The animals were stimulated 10 times on 10 consecutive days but with different tetanization strengths. Sprouting of the mossy fibres terminating in the CA3 region was significantly induced only in the group of ‘strongly’ tetanized animals, but not in that of ‘weakly’ tetanized animals, or in low‐frequency stimulated animals. Additionally, a novel form of potentiation which was previously found in pentylenetetrazol (PTZ)‐kindled animals was also observed in the group of ‘strongly’ and ‘weakly’ tetanized rats. Differences in duration of this potentiation were found between the two groups of animals tetanized with different strengths. The results further demonstrate that morphological and functional changes in the hippocampus, similar to those seen after kindling, can also occur in an activation paradigm leading to long‐lasting synaptic plasticity but not accompanied by seizure activity.
Relationships between image structure and gamma oscillations and synchronization in visual cortex of cats
Authors: Molotchnikoff Stéphane , Shumikhina Svetlana
Published: March 2003

The relationships between visual object configurations and interneuronal spike synchronization and gamma oscillations are examined in the present investigation. Cells were initially stimulated with moving, optimally oriented, single 20°‐long bars of light, centred on the compound receptive field of a pool of cortical neurons. When this kind of stimulus evoked intrinsic gamma oscillations and/or synchronization, we gradually fractured the original target. In addition, colinearity was ruptured by forming L‐ and T‐shaped configurations. All fractures and discontinuities were introduced well outside the excitatory receptive field. Multiunit activity in the visual cortex (areas 17 and 18) was recorded in anaesthetized cats. Recording sites were separated by 0.4–1.2 mm. The data analysis indicates that gamma oscillations follow a rule by which unfractured bars yielded the highest S/N ratios. Synchronization strength, as revealed by the central peak in cross‐correlograms, also seemed to depend upon stimulus configuration. However, the magnitude of the central peak failed to follow a consistent trend. For instance, the greatest magnitude of the central peak occurred for both colinear and orthogonal types of target. Our results support the notion that both gamma oscillations and neuronal synchronization are stimulus‐dependent.
Serotoninergic and noradrenergic axonal contacts associated with premotor interneurons in spinal pathways from group II muscle afferents
Authors: Maxwell D. J. , Riddell J. S. , Jankowska E.
Published: March 2003

We investigated the possibility that monoaminergic axons make contacts with spinal interneurons which project to motor nuclei and are monosynaptically activated by group II muscle afferents. Interneurons in midlumbar spinal segments of adult cats were characterized electrophysiologically and intracellularly labelled with tetramethylrhodamine dextran. Serotoninergic and noradrenergic axons were identified with immunofluorescence in sections containing labelled cells. Contacts between monoaminergic axons and interneurons were investigated with three‐colour confocal laser scanning microscopy and analysed with a computer reconstruction program. Cell bodies and dendritic trees of five cells were reconstructed and putative contacts were plotted. The average number of contacts formed by serotoninergic axons was 140 and the average number of noradrenergic contacts was 38. The majority (95%) of contacts were formed with dendrites; these were distributed over the entire dendritic tree, even on the most distal branches. These findings provide a morphological basis for the modulatory actions of monoamines on premotor spinal interneurons in pathways from group II muscle afferents.
(+)‐MCPG induces PKCε translocation in cortical synaptosomes through a PLD‐coupled mGluR
Authors: Pastorino L. , Colciaghi F. , Gardoni F. , Albani‐Torregrossa S. , Pellegrini‐Giampietro D. E. , Moroni F. , De Graan P. N. E. , Cattabeni F. , Di Luca M.
Published: March 2003

We have tested whether different agonists of metabotropic glutamate receptors could induce translocation of selective protein kinase C isozymes in nerve terminals. In rat cortical synaptosomes 1S,3R‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD; 100 μm) induced an increase in translocation to 124.6 ± 5.7% of basal unstimulated conditions of the Ca++‐independent protein kinase Cε, but not of the Ca++‐dependent isozyme β. This effect was counteracted by 1‐aminoindan‐1,5‐dicarboxylic acid (100 μm), an antagonist of metabotropic glutamate receptor 1. On the other hand, (+)‐α‐methyl‐4‐carboxyphenylglycine [(+)‐MCPG], an antagonist of metabotropic glutamate receptors group I and II, did not antagonize the effect of 1S,3R‐ACPD, and per se induced a translocation of protein kinase Cε of 164 ± 17.7% of basal unstimulated conditions. Because the (+)‐MCPG induction of protein kinase Cε translocation was not antagonized by 1‐aminoindan‐1,5‐dicarboxylic acid, it is suggested that 1S,3R‐ACPD and (+)‐MCPG activate this signal transduction pathway through distinct membrane receptors. Indeed (2‐[2′′‐carboxy‐3′‐phenylcyclopropyl]glycine)‐13 (300 nm), a new compound known to antagonize metabotropic glutamate receptors coupled to phospholipase D, was able to antagonize protein kinase Cε translocation induced by (+)‐MCPG. Moreover (+)‐MCPG directly induced phospholipase D activity, measured as [3H]phosphoethanol production in cortical synaptosomes. These data suggest that in cortical nerve terminals (i) distinct metabotropic glutamate receptors, coupled to different signal transduction pathways, are present, (ii) (+)‐MCPG is able to induce protein kinase Cε translocation, and that (iii) a metabotropic glutamate receptor associated to phospholipase D might influence translocation of protein kinase C in a calcium‐independent manner.
Association of neuropeptide Y Y1 receptors with glutamate‐positive and NPY‐positive neurons in rat hippocampal cultures
Authors: St‐Pierre Jacques‐André , Nouel Dominique , Dumont Yvan , Beaudet Alain , Quirion Rémi
Published: March 2003

The hippocampus is particularly enriched with neuropeptide tyrosine (NPY) and NPY receptors including the Y1, Y2 and Y5 subtypes. We have previously reported on the enrichment of cultured rat hippocampal neurons in specific [125I][Leu31,Pro34]PYY/BIBP3226‐sensitive (Y1) binding sites and Y1 receptor mRNAs [St‐Pierre et al. (1998) Br. J. Pharmacol., 123, p183]. We have now identified which cell types express the Y1 receptor. The majority of Y1 receptors, visualized using either the radiolabeled probe [125I][Leu31,Pro34]PYY or two antibodies directed against distinct domains of the Y1 receptor, was expressed in neurons as revealed by neuron‐specific enolase (NSE) immunostaining. One antibody was directed against the second extracelllular loop of the Y1 receptor (amino acids 185–203) whereas the second was directed against the intracellular C‐terminal loop (amino acids 355–382). The labelling was evident over both perikarya and processes. Neurons labelled by the various Y1 receptor probes were mostly glutamate‐positive as revealed by double immunostaining. Most interestingly, a number of NPY‐positive cultured hippocampal neurons were also enriched with the Y1 receptor, suggesting that this subtype may act as an autoreceptor to regulate NPY release in the hippocampus. These results thus provide an anatomical basis for the modulation of glutamate and NPY release by the Y1 receptor in the hippocampus.
Fast oscillations display sharper orientation tuning than slower components of the same recordings in striate cortex of the awake monkey
Authors: Frien Axel , Eckhorn Reinhard , Bauer Roman , Woelbern Thomas , Gabriel Andreas
Published: March 2003

We wanted to know whether fast oscillations (≈ 30–80 Hz) in striate cortex of awake monkeys show sharper orientation selectivity than (i) slower components, including spike rate modulations, and (ii) broad‐band signals of the same recordings. As fast oscillations are probably of cortical origin this may further clarify whether cortical network mechanisms are substantially involved in generating orientation selectivity. We recorded multi unit activity (MUA) and local field potentials (LFP, 1–140 Hz) by the same microelectrodes from upper layers of macaque striate cortex during visual stimulation with grating textures of different orientations. An orientation index (OI) was derived from the cortical responses in three frequency ranges (low, 0–11.7 Hz; medium, 11.7–31.3 Hz; and fast oscillations, 31.3–62.5 Hz) and for the broad‐band LFP and MUA power. (i) Both LFP and MUA fast oscillations reveal a higher orientation index than signal components in the low and medium frequency ranges. (ii) For MUA the orientation index was significantly higher with fast oscillations than for the lower frequency ranges and the initial broad‐band transient responses. (iii) LFPs show a significantly higher orientation index only for the fast oscillations during sustained activation compared with their broad‐band power during the transient responses. Thus, our main result is the sharper orientation tuning of fast oscillations in spike activities of local populations compared with slower components of the same broad‐band recordings. As fast oscillations occur synchronized in the awake monkey's striate cortex we assume that they have enhanced probability of activating successive stages of visual processing and hence contribute to the perception of orientation.
Functional coupling shows stronger stimulus dependency for fast oscillations than for low‐frequency components in striate cortex of awake monkey
Authors: Frien Axel , Eckhorn Reinhard
Published: March 2003

It has been argued that coupling among the neural signals activated by a visual object supports binding of local features into a coherent object perception. During visual stimulation by a grating texture we studied functional coupling by calculating spectral coherence among pairs of signals recorded in the striate cortex of awake monkeys. Multiple unit activity (MUA) and local field potentials (LFP, 1–140 Hz) were extracted from seven parallel broad band recordings. Spectral coherence was dominated by high‐frequency oscillations in the range 35–50 Hz and often by additional low‐frequency components (0–12 Hz). Functional coupling among separate cortical sites was more stimulus specific for MUA than for LFP: MUA coherence at high and low frequencies depended highly significantly on: (i) the similarity of the preferred orientations at the two sites − the more similar the higher the coherence; (ii) the orientation of the stimulus grating − with highest coherence at half angle between the preferred orientations at the two sites; (iii) cortical distance − coherence decreases to noise levels at ∼ 3 mm (MUA) and 6 mm (LFP). Coherence of fast oscillations did not depend on the degree of coaxiality of the orientation‐sensitive receptive fields, whereas low frequencies showed significant dependency. This indicates that different frequency components can engage different coupling networks in the striate cortex which probably support different coding tasks. Changes in average oscillation frequency with stimulus orientation were highly significant for fast oscillations while there was no dependency for low frequencies. Finally, stimulus‐related spectral power and coherence of fast oscillations were considerably higher than of low frequency components. Fast oscillations may therefore contribute more to feature binding and coding of object continuity than low‐frequency components, at least for texture surfaces as analysed here.
Developmental changes in astrocyte density in the macaque perifoveal region
Authors: Distler C. , Kopatz K. , Telkes I.
Published: March 2003

We studied astrocyte density both in the perifoveal region and in extrafoveal regions within the same distance of the optic disc (OD) over a time period from foveal pit formation (embryonic day E112) until 2 months after birth. The study was prompted by earlier observations that the adult macaque displays an almost astrocyte‐free region around the fovea which, however, at birth is occupied by astrocytes. Thus, we wanted to determine if the perifoveal region is invaded by astrocytes during early development to the same degree as other regions in the central retina, and how the reduction in density can be explained. From the earliest age we studied (embryonic day 112), less astrocytes were found in the perifovea than in other regions equidistant from the OD. In addition, the number of astrocytes steadily declined both in the perifovea and outside until birth. During the first week after birth, there was a further dramatic decline in perifoveal astrocyte density. Double‐labelling with glial fibrillary acidic protein (GFAP) immunocytochemistry and the TUNEL method showed that during the whole observation period astrocytes undergo DNA fragmentation and presumably die. However, the rate of TUNEL‐positive astrocytes did not significantly differ between perifovea and other regions equidistant to the OD, and at no time did we find a significant peak of apoptosis rate. Thus, the reduction in perifoveal astrocyte density cannot be explained by missing invasion or by selectively elevated apoptosis rates in the foveal and perifoveal regions. Alternative hypotheses are discussed.
Ageing alters intrahypothalamic release patterns of vasopressin and oxytocin in rats
Authors: Keck Martin E. , Hatzinger Martin , Wotjak Carsten T. , Landgraf Rainer , Holsboer Florian , Neumann Inga D.
Published: March 2003

The ageing process has been shown to have a profound impact on the hypothalamo–neurohypophysial system (HNS) and the hypothalamo–pituitary–adrenocortical (HPA) axis in humans as well as in rodents. Therefore, in this study, the intracerebral and peripheral release patterns of both vasopressin and oxytocin have been studied in aged male Wistar rats under basal conditions and in response to ethologically relevant stressors, using intracerebral microdialysis and chronic blood sampling techniques, respectively. Approximately a twofold higher basal release of arginine vasopressin (AVP) within the hypothalamic paraventricular nucleus (PVN), but not within the supraoptic nucleus (SON), was found in aged rats, whereas basal oxytocin (OXT) release did not differ in comparison with young rats. With increasing age the rise in intra‐PVN release of both AVP and OXT was blunted in response to forced swimming. In contrast, the intra‐SON release of AVP was unrelated to age. Simultaneously recorded basal secretion of both AVP and OXT from the neurohypophysis into blood was increased in aged rats, with a blunted OXT response to swim stress. Opposed to that, plasma AVP levels remained unchanged in both groups. Basal plasma levels of corticotropin (ACTH) and corticosterone were elevated in aged rats, whereas stress‐elicited ACTH and corticosterone responses were indistinguishable. These results indicate age‐related changes in the HNS and HPA axis with an enhanced basal activity opposed to a blunted response to stressors with increasing age. The increased basal release of AVP within the PVN suggests a role of intracerebral AVP in age‐associated alterations of HPA axis regulation.
Lack of glucocorticoids attenuates the self‐stimulation‐induced increase in the in vivo synthesis rate of dopamine but not serotonin in the rat nucleus accumbens
Authors: Nakahara Daiichiro , Nakamura Masato , Oki Yutaka , Ishida Yasushi
Published: March 2003

Our previous study demonstrated that intracranial self‐stimulation of the medial forebrain bundle can increase the in vivo synthesis turnover rate of dopamine (DA) and serotonin (5‐HT) in the nucleus accumbens of adrenal‐intact rats. The present study examined using microdialysis whether such increases in DA and 5‐HT syntheses are influenced by adrenal hormones, which are also activated following intracranial self‐stimulation. A decarboxylase inhibitor, NSD‐1015, was perfused through reversed microdialysis which enabled the simultaneous measurement of 3,4‐dihydroxyphenylalanine (DOPA) and 5‐hydroxytryptophan (5‐HTP) as an index of the in vivo turnover rate of DA and 5‐HT syntheses. Adrenalectomy (ADX) attenuated significantly the self‐stimulation‐induced increase in dialysate levels of DOPA but not 5‐HTP. Corticosterone (Cort) replacement reversed the attenuation in DOPA levels in adrenalectomized rats. The finding indicates that activation of DA synthesis in vivo in the nucleus accumbens during intracranial self‐stimulation is dependent on, whereas that of 5‐HT synthesis is independent of glucocorticoid modulation.
NFI in the development of the olfactory neuroepithelium and the regulation of olfactory marker protein gene expression.
Authors: Behrens M. , Venkatraman G. , Gronostajski R. M. , Reed R. R. , Margolis F. L.
Published: March 2003

Nuclear factor I (NFI) proteins are DNA‐binding transcription factors that participate in the tissue specific expression of various genes. They are encoded by four different genes (NFI‐A, B, C, and X) each of which generates multiple isoforms by alternative RNA splicing. NFI‐like binding sites have been identified in several genes preferentially expressed in olfactory receptor neurons. Our prior demonstration that NFI binds to these elements led to the hypothesis that NFI is involved in the regulation of these genes. To analyse the role of NFI in the regulation of olfactory neuron gene expression we have performed transient transfection experiments in HEK 293 cells using constructs that place luciferase expression under the control of an olfactory marker protein (OMP)‐promoter fragment containing the NFI binding site. In vitro mutagenesis of this site revealed a negative modulation of luciferase expression by endogenous NFI proteins in HEK 293 cells. In addition, we have used in situ hybridization to analyse the tissue and cellular distribution of the four NFI gene transcripts during pre‐ and postnatal mouse development. We have simultaneously characterized the expression of Pax‐6, and O/E‐1, transcription factors known to regulate the phenotype of olfactory receptor neurons. We demonstrate that all of these transcription factors vary in specific spatio–temporal patterns during the development of the olfactory system. These data on NFI activity, and on transcription factor expression, provide a basis to understand the role of NFI in regulating gene expression in olfactory receptor neurons.
Neurite morphogenesis of identified visual interneurons and its relationship to photoreceptor synaptogenesis in the flies, Musca domestica and Drosophila melanogaster
Authors: Meinertzhagen I. A. , Piper S. T. , Sun X. ‐J. , Fröhlich A.
Published: March 2003

The first neuropile, or lamina, of the fly's optic lobe comprises a model set of identified neurons that are arrayed in cylindrical modules, called cartridges. The cartridge acquires adult form only in the second half of the fly's pupal life. All cells are by then correctly located within each of the lamina's cartridges (Drosophila, Musca), becoming invested by glial cells after 75% of pupal development (P + 75%). In adult cartridges, two lamina cells, L1 and L2, receive input from photoreceptor terminals R1–R6, at so‐called tetrad synapses that form in the pupa when these cells' dendrites contact R1–R6. Single‐section electron microscopy (EM, Drosophila) and serial‐EM reconstructions of L1 and L2 (Musca) reveal relationships between the morphogenesis of L1/L2 dendrites and the formation of tetrads. Neurite outgrowth is initially (P + 55%) random and neurites are unbranched; many neurites invaginate surrounding terminals of R1–R6 but, later, embrace the outer surfaces of these. The maximum profusion of neurites at P + 74% coincides with peak numbers of nascent tetrads; neurites then branch vertically, in the lamina's depth. Later, neurites failing to reach R1–R6's outer surfaces regress. Down the length of their axons, L1 and L2's neurites initially form a random sequence, L1 partnering L1 as often as L2, etc., but beginning at P + 74%, L1 partners L2, and L2 partners L1, with progressive strictness. L1 has more neurites overall than L2. These observations are consistent with the following hypotheses: a neurite only survives if it contacts a presynaptic site; a synapse only survives if it progressively acquires the appropriate number and combination of postsynaptic neurites, culminating in a tetrad; an interaction exists between the neurites of L1 and L2, so that the growth of one respects the pattern of growth of the other.
Neuropsin regulates an early phase of Schaffer‐collateral long‐term potentiation in the murine hippocampus
Authors: Komai Shoji , Matsuyama Tomohiro , Matsumoto Kazumasa , Kato Keiko , Kobayashi Masayuki , Imamura Kazuyuki , Yoshida Shigetaka , Ugawa Shinya , Shiosaka Sadao
Published: March 2003

We found that neuropsin, an extracellular matrix serine protease, has a regulatory effect on Schaffer‐collateral long‐term potentiation (LTP) in the mouse hippocampus. Bath application of 1–170 n m recombinant neuropsin modulated early phase LTP in the Schaffer‐collateral pathway with a ‘bell‐shape’ dose–response curve. The maximum enhancing activity (134% of control LTP) was found at ∼ 2.5 nm. Bath application of a neutralizing antibody against neuropsin in the hippocampal slice resulted in a marked inhibition of the tetanus‐induced early phase of LTP. The in vivo continuous intraventricular infusion of an antisense oligonucleotide against neuropsin significantly reduced the amplitude of the tetanus‐induced early phase of LTP in vitro. Neuropsin did not directly change the N‐methyl d‐aspartate (NMDA) current. Thus, neuropsin appears to act as a regulatory molecule in the early phase of LTP via its proteolytic function on extracellular matrix rather than affecting NMDA receptor‐mediated calcium increase.
Previous experience of withdrawal from chronic diazepam ameliorates the aversiveness of precipitated withdrawal and reduces withdrawal‐induced c‐fos expression in nucleus accumbens
Authors: Dunworth Sarah J. , Mead Andy N. , Stephens David N.
Published: March 2003

Flumazenil (20 mg/kg, i.p.)‐precipitated withdrawal from chronic treatment with diazepam (DZP, 15 mg/kg, s.c. in sesame oil for 21 days) resulted in a decreased seizure threshold to the convulsant, pentylenetetrazole (PTZ), infused into the tail vein; withdrawal from 21‐day chronic diazepam treatment, interspersed with two periods of drug withdrawal, resulted in a greater decrease in convulsant threshold. A separate experiment showed that consumption of a sucrose solution immediately prior to precipitated withdrawal resulted in a decreased subsequent consumption of the sucrose solution; no such evidence of a conditioned taste aversion (CTA) was seen in mice given prior experience of withdrawal. Thus, prior experience of withdrawal enhanced the effects of a subsequent precipitated withdrawal in increasing seizure sensitivity, but weakened the ability of this withdrawal to serve as an aversive unconditioned stimulus (US). The weakening of the aversive properties of precipitated withdrawal may reflect habituation to the withdrawal stimulus, and was accompanied by a loss of the ability of withdrawal to induce c‐fos expression in the shell of the nucleus accumbens, an area sensitive to both novel, and stressful, as well as rewarding stimuli.
Involvement of the medial septum in stress‐induced relapse to heroin seeking in rats
Authors: Highfield David , Clements Alison , Shalev Uri , McDonald Robert , Featherstone Robert , Stewart Jane , Shaham Yavin
Published: March 2003

Intermittent footshock stress has been shown to reinstate extinguished drug‐taking behaviour in rats, but the brain areas involved in this effect are to a large degree unknown. Here we studied the role of the septum in stress‐induced reinstatement of heroin seeking. Rats were trained to self‐administer heroin for 9–10 days (three 3‐h sessions per day, 0.1 mg/kg per infusion). Following training, extinction sessions were given for 8–13 days by substituting saline for heroin, and then tests for reinstatement of heroin seeking were carried out. Reversible inactivation of the medial septum with tetrodotoxin (TTX; 1–5 ng, infused 25–40 min before the test sessions) reliably reinstated heroin seeking, mimicking the effect of 15 min of intermittent footshock. This effect of TTX was not observed after infusions made 1.5 mm dorsally into the lateral septum. In other experiments, it was found that infusions of a low, subthreshold dose of TTX (0.5 ng) into the medial septum, when combined with 2 min of footshock that in itself was ineffective, reinstated heroin seeking. Furthermore, electrical stimulation (400 μA pulses, 100 μs duration, 100 Hz frequency) of the medial septum during exposure to 10 min of intermittent footshock attenuated footshock‐induced reinstatement of heroin seeking. These data suggest a role for the medial septum in stress‐induced relapse to drug seeking. The septum is thought to be involved in neuronal processes underlying behavioural inhibition, thus we speculate that stressors provoke relapse by interfering with these processes.
Response properties of PMLS and PLLS neurons to simulated optic flow patterns
Authors: Li Bing , Li Bao‐Wang , Chen Yao , Wang Lian‐Hong , Diao Yun‐Cheng
Published: March 2003

The processing of optic flow information has been extensively investigated in the medial superior temporal area (MST) of the macaque. In the cat, the posteromedial area and the posterolateral area in the lateral suprasylvian cortex (PMLS and PLLS, respectively) have been suggested as likely participants according to their direction preferences to moving objects. In the present study, 203 PMLS and 123 PLLS neurons were tested with simulated optic flow patterns composed of random dots (including expansion and contraction, clockwise and counter‐clockwise rotation, and translation) and moving bar stimuli. About 90% of the neurons were found to be excited by the optic flow stimuli and most of them were multiple‐responsive to different flow patterns. Only 20–25% of the cells were selective to different optic flow modes, and in general, the direction preference was fairly modest. The selective cells showed stronger directionality to both flow field and moving bar than nonselective cells. However, the optic flow response properties in the PMLS and PLLS were not well correlated with the direction preference to moving bars. In accordance with previous findings, the PMLS was analogous to the middle temporal area of the macaque in many respects. As for the PLLS cells, they were sensitive to fewer types of stimuli, but responded better and more selectively to radial motion. All these results suggest that the two lateral suprasylvian areas are unlikely to be specialized for the analysis or discrimination of different flow patterns, but may play some kind of relay role in optic flow information processing.