bluuebunny/crossref_metadata_2025_split huggingface dataset:
Firing rate and theta‐phase coding by hippocampal pyramidal neurons during ‘space clamping’
Authors: Hirase Hajime , Czurkó András , Csicsvari Jozsef , Buzsáki György 
Published: March 2003

AbstractIn the hippocampus, spatial representation of the environment has been suggested to be coded by either the firing rate of pyramidal cell assemblies or the relative timing of the action potentials during the theta EEG cycle. Here, we used a behavioural ‘space clamp’ method, which involved the confinement of the actively running animal in a defined position in space (running wheel) to examine how ‘spatial’ and other inputs affect firing rate and timing of hippocampal CA1 pyramidal cells and interneurons. Nineteen per cent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel in a given direction (‘wheel’ cells). Spatial rotation of the apparatus showed that selective discharge of pyramidal cells in the wheel was under the combined influence of distal and apparatus cues. During steady running, both discharge rate and theta phase were constant. Rotation of the wheel apparatus resulted in a shift of both firing rate and preferred theta phase. The discharge frequency of ‘wheel’ cells increased threefold (on average) with increasing running velocity. In contrast, change in running speed had relatively little effect on the theta phase‐related discharge of ‘wheel’ cells. Our findings indicate that mechanisms that regulate rate and phase of spikes are overlapping but not necessarily identical.
Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys
Authors: Meunier Martine , Bachevalier Jocelyne , Murray Elisabeth A. , Málková Ludiše , Mishkin Mortimer 
Published: March 2003

AbstractAll previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibres of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala with those induced by fibre‐sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of defence, aggression, submission and approach responses. In unoperated controls, defence and approach behaviours were elicited by all four stimuli, ‘social’ and inanimate alike, whereas aggression and submission responses occurred only in the presence of the two ‘social’ stimuli. Furthermore, all defence reactions were reduced with an attractive inanimate item, while freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioural changes as those with aspiration lesions, i.e. reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two‐thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, because some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fibre damage.
Doc2α is an activity‐dependent modulator of excitatory synaptic transmission
Authors: Sakaguchi Gaku , Manabe Toshiya , Kobayashi Katsunori , Orita Satoshi , Sasaki Takuya , Naito Akira , Maeda Miki , Igarashi Hisanaga , Katsuura Goro , Nishioka Hideo , Mizoguchi Akira , Itohara Shigeyoshi , Takahashi Tomoyuki , Takai Yoshimi 
Published: March 2003

AbstractDoc2α is a synaptic vesicle‐associated Ca2 + ‐binding protein. To study the role of Doc2α in synaptic transmission and modulation, we generated homozygous null Doc2α mutant mice. In the CA1 region of hippocampal slices in the mutant mice, excitatory synaptic responses evoked with prolonged 5 Hz stimulation showed a significantly larger frequency facilitation followed by a steeper depression than those in wild‐type mice, whereas there was no difference in synaptic transmission at lower frequencies or in paired‐pulse facilitation. These results suggest that Doc2α regulates synaptic transmission when high Ca2 +  concentrations in the presynaptic terminal are sustained. Furthermore, the mutant mice showed impairment in long‐term potentiation and passive avoidance task. Thus, Doc2α may regulate transmitter release during repetitive synaptic activation, thereby contributing to memory formation.
Activity‐dependent formation of perforated synapses in cultured hippocampal neurons
Authors: Neuhoff Henrike , Roeper Jochen , Schweizer Michaela 
Published: March 2003

AbstractThe study investigated the formation of perforated synapses in rat hippocampal cell cultures. Perforated synapses are defined by their discontinuous postsynaptic densities (PSDs) and are believed to occur in parallel with changes in synaptic activity and possibly also synaptic efficacy. Several in vivo studies have demonstrated an increase in the frequency of perforated synapses induced by development and environmental stimulation as well as long‐term potentiation (LTP). Also in in vitro brain slices, LTP was associated with an elevated number of perforated spine synapses. Our study demonstrated for the first time that the formation of perforated synapses can be induced by a short‐term increase in spontaneous neural activity in a hippocampal cell culture model. Stimulation with the GABAA‐antagonist picrotoxin (PTX) induced a significant increase in the percentage of perforated synapses. This strong increase was blocked when APV was added together with PTX, indicating that the formation of perforated synapses depended on the activation of NMDA receptors. We also showed that inhibition of the tissue type plasminogen activator (tPA‐stop/PAI‐1) significantly interfered with the activity‐induced increase in perforated synapses. This implies that the proteolytic activities of tPA might be involved in steps which are downstream from the NMDA receptor‐mediated synaptic plasticity leading to structural changes at synaptic contacts. In contrast, even long‐term inhibition of electrical network activity by tetrodotoxin had no effect on the number of perforated synapses, but almost completely abolished the formation of spine synapses. These results indicate that a short‐term increase in neural activity via NMDA receptors and a proteolytic cascade involving tPA lead to the formation of perforated synapses.
Age‐related behavioural deficits in transgenic mice expressing the HIV‐1 coat protein gp120
Authors: D'Hooge R. , Franck F. , Mucke L. , De Deyn P. P. 
Published: March 2003

AbstractTransgenic mice expressing HIV‐1 coat glycoprotein gp120 in brain glial cells were previously shown to display AIDS dementia‐like neuropathological changes and reduced hippocampal long‐term potentiation. In this report, neuromotor and cognitive performance in 3‐ and 12‐month‐old gp120‐expressing mice was compared with wildtype controls. Rotarod and cage activity measures showed no significant differences between transgenic animals and controls of either age. Open field activity was slightly altered in 12‐month‐old gp120 animals (reduced corner crossings and dwell in centre), but not in the 3‐month‐olds. Cognitive assessment using the Morris water maze showed unimpaired performance in 3‐month‐old mice during acquisition and (no‐platform) probe trials. In 12‐month‐old gp120 animals, escape latency and swimming velocity during the acquisition trials were significantly reduced, but performance improved at roughly the same rate as in control animals. However, the probe trials revealed a highly significant reduction in spatial retention in transgenic mice of this age. This demonstration of age‐dependent impairments in open field activity and spatial reference memory may relate to cognitive and neuromotor deficits seen in a proportion of HIV‐1‐infected individuals.
Contrasting mechanisms of action and sensitivity to antipsychotics of phencyclidine versus amphetamine: importance of nucleus accumbens 5‐HT2A sites for PCP‐induced locomotion in the rat
Authors: Millan M. J. , Brocco M. , Gobert A. , Joly F. , Bervoets K. , Rivet J. ‐M. , Newman‐Tancredi A. , Audinot V. , Maurel S. 
Published: March 2003

AbstractIn the present study, the comparative mechanisms of action of phencyclidine (PCP) and amphetamine were addressed employing the parameter of locomotion in rats. PCP‐induced locomotion (PLOC) was potently blocked by the selective serotonin (5‐HT)2A vs. D2 antagonists, SR46349, MDL100,907, ritanserin and fananserin, which barely affected amphetamine‐induced locomotion (ALOC). In contrast, the selective D2 vs. 5‐HT2A antagonists, eticlopride, raclopride and amisulpride, preferentially inhibited ALOC vs. PLOC. The potency of these drugs and 12 multireceptorial antipsychotics in inhibiting PLOC vs. ALOC correlated significantly with affinities at 5‐HT2A vs. D2 receptors, respectively. Amphetamine and PCP both dose dependently increased dialysate levels of dopamine (DA) and 5‐HT in the nucleus accumbens, striatum and frontal cortex (FCX) of freely moving rats, but PCP was proportionally more effective than amphetamine in elevating levels of 5‐HT vs. DA in the accumbens. Further, whereas microinjection of PCP into the accumbens elicited locomotion, its introduction into the striatum or FCX was ineffective. The action of intra‐accumbens PCP, but not intra‐accumbens amphetamine, was abolished by SR46349 and clozapine. Parachloroamphetamine, which depleted accumbens pools of 5‐HT but not DA, likewise abolished PLOC without affecting ALOC. In contrast, intra‐accumbens 6‐hydroxydopamine (6‐OHDA), which depleted DA but not 5‐HT, abolished ALOC but only partially attenuated PLOC. In conclusion, PLOC involves (indirect) activation of accumbens‐localized 5‐HT2A receptors by 5‐HT. PLOC is, correspondingly, more potently blocked than ALOC by antipsychotics displaying marked affinity at 5‐HT2A receptors.
Genetic and epigenetic regulation of NMDA receptor expression in the rat visual cortex
Authors: Nase Gabriele , Weishaupt Jochen , Stern Peter , Singer Wolf , Monyer Hannah 
Published: March 2003

AbstractThe susceptibility of cortical networks to use‐dependent modifications declines with age (critical period) and this decline of neuronal plasticity during development is paralleled by the shortening of NMDA receptor EPSCs. We showed previously in the somatosensory cortex that the shortening of NMDA receptor kinetics correlates with a developmentally‐regulated increase in the NR2A subunit expression. Here we examine whether this developmental regulation of NR2A expression is related to the duration of critical periods and whether it is influenced by experience. Functional NMDA receptors and their molecular characteristics are studied in identified layer IV neurons of rat visual cortex. In this structure the time course of the critical period differs from that in the somatosensory cortex and can be changed by sensory deprivation, thus permitting examination of correlations between the time course of receptor expression and the duration of the critical period. We find that the developmental expression of the NR2A subunit is delayed compared with the somatosensory cortex, in agreement with the prolonged critical period in the visual cortex. Moreover, sensory deprivation further delays the developmental change in the NMDA receptor subunit composition, demonstrating the activity dependence of this process and strengthening the correlation between changes in subunit composition and the time course of the critical period.
Hippocampal Cajal–Retzius cells project to the entorhinal cortex: retrograde tracing and intracellular labelling studies
Authors: Ceranik Katja , Deng Jinbo , Heimrich Bernd , Lübke Joachim , Zhao Shanting , Förster Eckart , Frotscher Michael 
Published: March 2003

AbstractCajal–Retzius (CR) cells are characteristic horizontally orientated, early‐generated transient neurons in the marginal zones of the neocortex and hippocampus that synthesize the extracellular matrix protein reelin. They have been implicated in the pathfinding of entorhino‐hippocampal axons, but their role in this process remained unclear. Here we have studied the axonal projection of hippocampal CR cells. Following injection of the carbocyanine dye DiI into the entorhinal cortex of aldehyde‐fixed rat embryos and young postnatal rats, neurons in the outer molecular layer of the dentate gyrus and stratum lacunosum‐moleculare of the hippocampus proper with morphological characteristics of CR cells were retrogradely labelled. In a time course analysis, the first retrogradely labelled CR cells were observed on embryonic day 17. This projection of hippocampal CR cells to the entorhinal cortex was confirmed by retrograde tracing with Fast Blue in new‐born rats and by intracellular biocytin filling of CR cells in acute slices from young postnatal rat hippocampus/entorhinal cortex and in entorhino‐hippocampal slice cocultures using infrared videomicroscopy in combination with the patch‐clamp technique. In double‐labelling experiments CR cells were identified by their immunocytochemical staining for reelin or calretinin, and their interaction with entorhino‐hippocampal axons labelled by anterograde tracers was analysed. Future studies need to investigate whether this early transient projection of hippocampal CR cells to the entorhinal cortex is used as a template by the entorhinal axons growing to their target layers in the hippocampus.
Sensorimotor transformation in cat nociceptive withdrawal reflex system
Authors: Levinsson Anders , Garwicz Martin , Schouenborg Jens 
Published: March 2003

AbstractThe withdrawal reflex system of higher vertebrates has been extensively used as a model for spinal sensorimotor integration, nociceptive processing and plasticity. In the rat, the nociceptive withdrawal reflex system appears to have a modular organization. Each reflex module controls a single muscle or a few synergistic muscles, and its cutaneous receptive field corresponds to the skin area withdrawn upon contraction of the effector muscle(s) when the limb is in the standing position. This organization principle is at odds with the ‘flexion reflex’ concept postulated from cat studies. To assess the generality of the modular organization principle we have therefore re‐examined the cutaneous input to the withdrawal reflex system of the cat. The cutaneous receptive fields of hindlimb and forelimb muscles were mapped using calibrated noxious pinch stimulation and electromyographic recording technique in barbiturate anaesthetized animals. The investigated muscles had specific cutaneous receptive fields that appeared to correspond to the area of the skin withdrawn upon contraction of the muscle when the limb is in the standing position. The spatial organization of receptive fields in the cat was similar to that in the rat. However, differences in gain properties of reflexes to some anatomically equivalent muscles in the two species were observed, possibly reflecting adaptations to the biomechanics characteristic of the digitigrade and plantigrade stance in cats and rats, respectively. Implications of the findings for the generality of the modular organization of the withdrawal reflex system and for its adaptive properties are discussed.
Short‐lasting conditioned stimulus applied to the middle cerebellar peduncle elicits delayed conditioned eye blink responses in the decerebrate ferret
Authors: Svensson P. , Ivarsson M. 
Published: March 2003

AbstractIn delay eye blink conditioning, the conditioned stimulus (CS) ends at the time of the unconditioned stimulus (US). If the CS duration is decreased, there will be a ‘trace’ period with no ongoing CS before the onset of the US. During this period some neural activity has to continue after the CS offset to: (i) permit association between the CS and the US; and (ii) elicit a conditioned response appearing after the CS offset. In this study we test the role of the cerebellum in maintaining CS activity required for eliciting a conditioned response after the CS offset. Decerebrate ferrets were trained in a delay conditioning paradigm with an electrical stimulation of the forelimb as CS and of the periorbital area as US. The conditioned responses in the upper eyelid were monitored with electromyographical techniques. In well‐trained animals, test CSs of short duration down to 0.2 ms were applied to the forelimb or the middle cerebellar peduncle, while the interstimulus interval between CS onset and US onset was kept constant at 300 ms. Test CSs of short duration applied to the forelimb elicited conditioned responses. More importantly, also a short‐lasting CS to the middle cerebellar peduncle could elicit conditioned responses. The results indicate that precerebellar CS pathways are not required for maintaining the neural activity that elicits conditioned responses after the CS offset. It is suggested that neurons maintaining such activity are located in the cerebellum, either the cortex alone or the cortex and the deep nuclei.
Orientation topography of layer 4 lateral networks revealed by optical imaging in cat visual cortex (area 18)
Authors: Yousef Tagrid , Bonhoeffer Tobias , Kim Dae‐Shik , Eysel Ulf T. , Tóth Éva , Kisvárday Zoltán F. 
Published: March 2003

AbstractThe functional specificity of corticocortical connections with respect to the topography of orientation selectivity was studied by optical imaging of intrinsic signals and bulk injections of fluorescent latex beads (green and red) and biocytin into layer 4. The distributions of retrogradely labelled cells and anterogradely labelled axon terminals were histologically reconstructed from all cortical laminae, and the resulting anatomical maps compared with the optically imaged functional maps. Layer 4 injections produced extensive horizontal labelling up to 2–3 mm from the injection centres albeit without the clear patchy pattern described after layer 2/3 injections (Gilbert & Wiesel 1989, J. Neurosci., 9, 2432–2442; Kisvárday et al. 1997, Cerebral Cortex, 7, 605–618). The functional (orientation) distribution of the labelled projections was analysed according to laminar location and lateral spread. With regard to the former, no major difference in the orientation topography between supragranular‐ (upper tier), granular‐ (middle tier) and infragranular (lower tier) layers was seen. Laterally, proximal and distal projections were distinguished and further dissected into three orientation categories, iso‐ (± 30°), oblique‐ (± 30–60°) and cross‐orientations (± 60–90°) with respect to the orientation preference at the injection sites. The majority of distal connections (retrograde and anterograde) was equally distributed across orientations (35.4% iso‐, 33.7% oblique‐, and 30.9% cross‐orientations) that are equivalent with a preponderance to dissimilar orientations (oblique‐ and cross‐orientations, 64.6%). In one case, distal excitatory and inhibitory connections could be morphologically distinguished. For both categories, a marked bias to dissimilar orientations was found (excitatory, 63.7%; inhibitory, 86.6%). Taken together, these results suggest that the long‐range layer 4 circuitry has a different functional role from that of the iso‐orientation biased (52.9%, Kisvárday et al. 1997, Cerebral Cortex, 7, 605–618) layer 2/3 circuitry, and is perhaps involved in feature difference‐based mechanisms, e.g. figure ground segregation.
Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes
Authors: Honnorat Jérôme , Byk Tamara , Kusters Inca , Aguera Michèle , Ricard Damien , Rogemond Véronique , Quach Tam , Aunis Dominique , Sobel André , Mattei Marie‐Geneviève , Kolattukudy Pappachan , Belin Marie‐Françoise , Antoine Jean Christophe 
Published: March 2003

AbstractAnti‐CV2 autoantibodies have recently been discovered in patients with paraneoplastic neurological diseases (PND). These disorders are associated with neuronal degeneration, mediated by autoimmune processes, in patients with systemic cancer. Anti‐CV2 autoantibodies recognize a brain protein of 66 kDa developmentally regulated and specifically expressed by a subpopulation of oligodendrocytes in the adult brain. Here, we demonstrate that anti‐CV2 sera recognize several post‐translationally modified forms of Ulip4/CRMP3, a member of a protein family related to the axonal guidance and homologous to the Unc‐33 gene product in Caenorhabditis elegans. The sequence of the human Ulip4/CRMP3 was determined and the gene localized to chromosome 10q25.2–q26, a region mutated in glioblastomas and containing tumour suppressor genes. The identification of the Ulip/CRMP proteins as recognized by anti‐CV2 sera should provide new insights into the role of Ulip/CRMPs in oligodendrocytes and into pathophysiology of PND.
Activity‐dependent neurotransmitter release kinetics: correlation with changes in morphological distributions of small and large vesicles in central nerve terminals
Authors: Leenders A. G. Miriam , Scholten Greet , Wiegant Victor M. , Da Silva Fernando H. Lopes , Ghijsen Wim E. J. M. 
Published: March 2003

AbstractIn central nerve terminals transmitter release is tightly regulated and thought to occur in a number of steps. These steps include vesicle mobilization and docking prior to neurotransmitter release. Intrasynaptic changes in vesicle distribution were determined by electron microscopical analysis and neurotransmitter release was monitored by biochemical measurements. We correlated K + ‐induced changes in distribution of small and large vesicles with the release of their transmitters. For small synaptic vesicles, amino acid release as well as recruitment to and docking at the active zone were activated within 1 s of depolarization. In contrast, the disappearance of large dense‐cored vesicles and the release of the neuropeptide cholecystokinin were much slower, and no docking was observed. Studies with diverse Ca2 +  channel blockers indicated that mobilization and neurotransmitter release from both vesicle types were regulated by multiple Ca2 +  channels, although in different ways. Neurotransmitter release from small synaptic vesicles was predominantly regulated by P‐type Ca2 +  channels, whereas primarily Q‐type Ca2 +  channels regulated neurotransmitter release from large dense‐cored vesicles. The different Ca2 +  channnel types directly regulated mobilization of and neurotransmitter release from small synaptic vesicles whereas, by their cooperativity in raising the intracellular Ca2 +  concentration above release threshold, they more indirectly regulated large dense‐cored vesicle exocytosis.