bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cortically evoked secondary depolarization affects the integrative properties of thalamic reticular neurons
Authors: Fuentealba Pablo , Crochet Sylvain , Steriade Mircea 
Published: November 2004

AbstractCorticothalamic terminals on thalamic reticular (RE) neurons account for most synapses from afferent pathways onto this nucleus and these inputs are more powerful than those from axon collaterals of thalamocortical neurons. Given the supremacy of cortical inputs, we analysed here the characteristics and possible mechanisms underlying a secondary component of the cortically elicited depolarization in RE neurons, recorded in cats under barbiturate anesthesia. Electrical stimulation of corticothalamic axons in the internal capsule evoked fixed and short‐latency excitatory postsynaptic potentials (EPSPs) that, by increasing stimulation intensity and at hyperpolarized levels (< −70 mV), developed into low‐threshold spikes and spindle oscillations. The threshold for spindle oscillations was 60% higher than that required for evoking minimal EPSPs. The evoked EPSPs included a secondary depolarizing component, which appeared ∼ 5 ms after the peak of the initial component and was voltage dependent, i.e. most prominent between −70 mV and −85 mV, while being greatly reduced or absent at more hyperpolarized levels. The secondary depolarizing component was sensitive to QX‐314 in the recording micropipette. We suggest that the secondary component of cortically evoked EPSPs in RE neurons is due to the dendritic activation of T‐currents, with a probable contribution of the persistent Na+ current. This late component affected the integrative properties of RE neurons, including their spiking output and temporal summation of incoming cortical inputs.
Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition
Authors: Vaynman Shoshanna , Ying Zhe , Gomez‐Pinilla Fernando 
Published: November 2004

AbstractWe found that a short exercise period enhanced cognitive function on the Morris water maze (MWM), such that exercised animals were significantly better than sedentary controls at learning and recalling the location of the platform. The finding that exercise increased brain‐derived neurotrophic factor (BDNF), a molecule important for synaptic plasticity and learning and memory, impelled us to examine whether a BDNF‐mediated mechanism subserves the capacity of exercise to improve hippocampal‐dependent learning. A specific immunoadhesin chimera (TrkB‐IgG), that mimics the BDNF receptor, TrkB, to selectively bind BDNF molecules, was used to block BDNF in the hippocampus during a 1‐week voluntary exercise period. After this, a 2‐trial‐per‐day MWM was performed for 5 consecutive days, succeeded by a probe trial 2 days later. By inhibiting BDNF action we blocked the benefit of exercise on cognitive function, such that the learning and recall abilities of exercising animals receiving the BDNF blocker were reduced to sedentary control levels. Inhibiting BDNF action also blocked the effect of exercise on downstream systems regulated by BDNF and important for synaptic plasticity, cAMP response‐element‐binding protein (CREB) and synapsin I. Specific to exercise, we found an association between CREB and BDNF expression and cognitive function, such that animals who were the fastest learners and had the best recall showed the highest expression of BDNF and associated CREB mRNA levels. These findings suggest a functional role for CREB under the control of BDNF in mediating the exercise‐induced enhancement in learning and memory. Our results indicate that synapsin I might also contribute to this BDNF‐mediated mechanism.
Intrinsic and spontaneous neurogenesis in the postnatal slice culture of rat hippocampus
Authors: Kamada Maki , Li Ren‐Yong , Hashimoto Mika , Kakuda Masaaki , Okada Hiroshi , Koyanagi Yoshio , Ishizuka Toru , Yawo Hiromu 
Published: November 2004

AbstractOrganotypic slice culture preserves the morphological and physiological features of the hippocampus of live animals for a certain time. The hippocampus is one of exceptional regions where neurons are generated intrinsically and spontaneously throughout postnatal life. We investigated the possibility that neurons are generated continuously at the dentate granule cell layer (GCL) in slice culture of the rat hippocampus. Using 5‐bromodeoxyuridine (BrdU) labelling and retrovirus vector transduction methods, the phenotypes of the newly generated cells were identified immunohistochemically. At 4 weeks after BrdU exposure, BrdU‐labelled cells were found in the GCL and were immunoreactive with a neuronal marker, anti‐NeuN. There were fibrils immunoreactive with anti‐glial fibrillary acidic protein (GFAP), an astrocyte marker, in the layer covering the GCL and occasionally encapsulated BrdU‐labelled nuclei. When the newly divided cells were marked with the enhanced green fluorescent protein (EGFP) using a retrovirus vector, these cells had proliferative abilities throughout the following 4‐week cultivation period. Four weeks after the inoculation, the EGFP‐expressing cells consisted of various phenotypes of both early and late stages of differentiation; some were NeuN‐positive cells with appearances of neurons in the GCL and some were immunoreactive with anti‐Tuj1, a marker of immature neurons. Some EGFP‐expressing cells were immunoreactive with anti‐GFAP or anti‐nestin, a marker of neural progenitors. The present study suggests that slice cultures intrinsically retain spontaneous neurogenic abilities for their cultivation period. The combination of slice culture and retrovirus transduction methods enable the newly divided cells to be followed up for a long period.
Are switches in perception of the Necker cube related to eye position?
Authors: Einhäuser Wolfgang , Martin Kevan A. C. , König Peter 
Published: November 2004

AbstractThe issue of the relation of eye position to perceptual reversals of the ambiguous figure of the ‘Necker cube’ dates back to Necker's original article [L.A. Necker (1832) The London & Edinburgh Philosophical Magazine and Journal of Science, 1, 329–337]. Despite the investigations of many distinguished psychophysicists since then, the question of whether perceptual switching is a cause or a consequence of associated changes in eye position has remained a matter of debate. In the present study we overcame methodological problems that have bedevilled many previous studies. We avoided any instruction that could interfere with the human subjects' free viewing of the Necker cube, tracked the eye position precisely and used biased versions of the cube that produced unambiguous percepts to determine how each subject actually looked at the cube. We show that, under these free‐viewing conditions, there is a close link between the perception of the Necker cube and eye position. The average eye position of most subjects is at an extreme value at about the time when the subject's perception switches. From the biased cube trials we can infer that the polarity of the extreme corresponds to the percept which the subject had before the switch. These data indicate a bidirectional coupling between eye position and perceptual switching so that, after a subject's perceptual state changes, their eye position shifts to view the newly established percept. When the eye position approaches the corresponding extreme, the percept, in turn, becomes more and more likely to switch. This result suggests that the changed eye position itself might provide a negative feedback signal that suppresses the percept.
BM88 is an early marker of proliferating precursor cells that will differentiate into the neuronal lineage
Authors: Koutmani Yassemi , Hurel Catherine , Patsavoudi Evangelia , Hack Michael , Gotz Magdalena , Thomaidou Dimitra , Matsas Rebecca 
Published: November 2004

AbstractProgression of progenitor cells towards neuronal differentiation is tightly linked with cell cycle control and the switch from proliferative to neuron‐generating divisions. We have previously shown that the neuronal protein BM88 drives neuroblastoma cells towards exit from the cell cycle and differentiation into a neuronal phenotype in vitro. Here, we explored the role of BM88 during neuronal birth, cell cycle exit and the initiation of differentiation in vivo. By double‐ and triple‐labelling with the S‐phase marker BrdU or the late G2 and M‐phase marker cyclin B1, antibodies to BM88 and markers of the neuronal or glial cell lineages, we demonstrate that in the rodent forebrain, BM88 is expressed in multipotential progenitor cells before terminal mitosis and in their neuronal progeny during the neurogenic interval, as well as in the adult. Further, we defined at E16 a cohort of proliferative progenitors that exit S phase in synchrony, and by following their fate for 24 h we show that BM88 is associated with the dynamics of neuron‐generating divisions. Expression of BM88 was also evident in cycling cortical radial glial cells, which constitute the main neurogenic population in the cerebral cortex. In agreement, BM88 expression was markedly reduced and restricted to a smaller percentage of cells in the cerebral cortex of the Small eye mutant mice, which lack functional Pax6 and exhibit severe neurogenesis defects. Our data show an interesting correlation between BM88 expression and the progression of progenitor cells towards neuronal differentiation during the neurogenic interval.
A role for ERKII in synaptic pattern selectivity on the time‐scale of minutes
Authors: Ajay Sriram M. , Bhalla Upinder S. 
Published: November 2004

AbstractStimulus reinforcement strengthens learning. Intervals between reinforcement affect both the kind of learning that occurs and the amount of learning. Stimuli spaced by a few minutes result in more effective learning than when massed together. There are several synaptic correlates of repeated stimuli, such as different kinds of plasticity and the amplitude of synaptic change. Here we study the role of signalling pathways in the synapse on this selectivity for spaced stimuli. Using the in vitro hippocampal slice technique we monitored long‐term potentiation (LTP) amplitude in CA1 for repeated 100‐Hz, 1‐s tetani. We observe the highest LTP levels when the inter‐tetanus interval is 5–10 min. We tested biochemical activity in the slice following the same stimuli, and found that extracellular signal‐regulated kinase type II (ERKII) but not CaMKII exhibits a peak at about 10 min. When calcium influx into the slice is buffered using AM‐ester calcium dyes, amplitude of the physiological and biochemical response is reduced, but the timing is not shifted. We have previously used computer simulations of synaptic signalling to predict such temporal tuning from signalling pathways. In the current study we consider feedback and feedforward models that exhibit temporal tuning consistent with our experiments. We find that a model incorporating post‐stimulus build‐up of PKM zeta acting upstream of mitogen‐activated protein kinase is sufficient to explain the observed temporal tuning. On the basis of these combined experimental and modelling results we propose that the dynamics of PKM activation and ERKII signalling may provide a mechanism for functionally important forms of synaptic pattern selectivity.
Cellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neurons
Authors: Baloui Hasna , Von Boxberg Ysander , Vinh Joëlle , Weiss Stefan , Rossier Jean , Nothias Fatiha , Stettler Olivier 
Published: November 2004

AbstractThe 67‐kDa LR protein was originally discovered as a non‐integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67‐kDa LR and its related ‘precursor’ form 37‐kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie‐infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67‐kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin‐1 but also with brain regions classically associated with prion‐related neurodegeneration. In contrast to LR, the 37‐kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane‐associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin‐immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt‐Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions.
Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia
Authors: Sessa Giuseppina , Podini Paola , Mariani Margherita , Meroni Alessandra , Spreafico Roberto , Sinigaglia Francesco , Colonna Marco , Panina Paola , Meldolesi Jacopo 
Published: November 2004

AbstractTogether with its adaptor protein, the adaptor protein of 12 kDa also known as KARAP and TYROBP (DAP12), triggering r (TREM2) is a stimulatory membrane receptor of the immunoglobulin/lectin‐like superfamily, well known in myeloid cells. In humans, however, loss‐of‐function mutations of TREM2/DAP12 leave myeloid cells unaffected but induce an autosomal recessive disease characterized, together with bone cysts, by a spectrum of pathological lesions in the cortex, thalamus and basal ganglia with clinical symptoms of progressive dementia (polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy). Nothing was known about the role of TREM2/DAP12 in brain cell biology and physiology. By confocal immunocytochemistry we demonstrate that, in both human and mouse cerebral cortex, TREM2/DAP12, strongly expressed by microglia, is also present in a fraction of neurons but not in astrocytes and oligodendrocytes. In contrast, in the hippocampal cortex TREM2‐expressing neurons are rare. Both in neurons and microglia the receptor appears to be located mostly intracellularly in a discrete compartment(s) partially coinciding with (or adjacent to) the Golgi complex/trans‐Golgi network. Four nerve cell lines were identified as expressing the intracellular receptor system. In living human microglia CHME‐5 and glioblastoma T98G cells, activation of TREM2 by its specific antibody induced [Ca2+]i responses, documenting its surface expression and functioning. Surface expression of TREM2, low in resting CHME‐5 and T98G cells, increases significantly and transiently (60 min) when cells are stimulated by ionomycin, as revealed by both surface biotinylation and surface immunolabeling. Our results provide the first information about the expression, distribution (mostly intracellular) and functioning of TREM2/DAP12 system in nerve cells, a necessary step in the understanding of the cellular mechanisms affected in polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy.
Altered morphological and electrophysiological properties of Cajal–Retzius cells in cerebral cortex of embryonic Presenilin‐1 knockout mice
Authors: Kilb Werner , Hartmann Dieter , Saftig Paul , Luhmann Heiko J. 
Published: November 2004

AbstractMutations of Presenilin‐1 are the major cause of familial Alzheimer's disease. Presenilin‐1 knockout (PS1–/–) mice develop severe cortical dysplasia related to human type 2 lissencephaly. This overmigration syndrome has been attributed to the premature loss of Cajal–Retzius cells (CRcs), pioneer neurons required for the termination of radial neuronal migration. To elucidate the potential cellular mechanisms responsible for this premature neuronal loss, we investigated the morphological and electrophysiological properties of visually identified CRcs of wild‐type (WT) and PS1–/– mouse brains at embryonic day 16.5. The density of CRcs was substantially reduced in the cerebral cortex of PS1–/–. In PS1–/– CRcs the number of axonal branches was significantly increased to 12.5 ± 4.9 (n = 8; WT, 4.0 ± 1.4, n = 12), while no differences in dendritic branching and total length of dendritic and axonal compartments were observed. Additionally, the resting membrane potential of PS1–/– CRcs was significantly depolarized (−48.3 ± 1.7 mV; n = 23) in contrast to WT CRcs (−57.9 ± 2.1 mV; n = 38). Active membrane properties were not affected by PS1 deficiency. CRcs of both genotypes showed spontaneous postsynaptic currents that could be completely blocked by 100 µm bicuculline and were unaffected by glutamatergic antagonists, suggesting that they were mediated by GABAA receptors. These results demonstrate that axonal branching and resting membrane potential of CRcs was affected in embryonic cerebral cortex of PS1–/– mice. The depolarized membrane potential observed in PS1–/– CRcs may increase the susceptibility to neuronal death, thus facilitating the premature loss of CRcs in PS1–/– mice.
Acute improvement of hand sensibility after selective ipsilateral cutaneous forearm anaesthesia
Authors: Björkman Anders , Rosén Birgitta , Lundborg Göran 
Published: November 2004

AbstractThe cortical representation of body parts is constantly modulated in response to the afferent input, and acute deafferentation of a body part results in bilateral cortical reorganization. To study the effects on hand function of right forearm anaesthesia, we investigated ten human subjects (group 1) for perception of touch, tactile discrimination and grip strength in the right (ipsilateral) and left (contralateral) hand before, during and 24 h after forearm skin anaesthesia with a local anaesthetic cream (EMLA®). Ten age‐matched controls (group 2) were investigated in the same way but received placebo. In group 1 a significant improvement was seen in tactile discrimination in the ipsilateral hand compared to base line (P = 0.009) and compared to group 2 (P = 0.006). The improvement in tactile discrimination remained for at least 24 h after anaesthesia. Perception of touch, was improved during anaesthesia compared to baseline values in group 1 (P = 0.046) and remained for at least 24 h. Grip strength did not change. These findings suggest that transient selective deafferentation of an extremity results in enhanced sensory functions of the functionally preserved parts of the same extremity, presumably as a result of expansion of adjacent cortical territories. Such rapid functional changes suggest unmasking of pre‐existing synaptic connections as the mechanism underlying the acute modulation of sensory functions in the hand. Our findings open new perspectives for sensory re‐education and rehabilitation following injury to the peripheral and central nervous system.
Post‐training intrabasolateral amygdala infusions of dopamine modulate consolidation of inhibitory avoidance memory: involvement of noradrenergic and cholinergic systems
Authors: LaLumiere Ryan T. , Nguyen Linda T. , McGaugh James L. 
Published: November 2004

AbstractThere is extensive evidence that several neurotransmitter systems within the basolateral amygdala (BLA) influence memory consolidation. The present study investigated the influence of dopamine (DA) in the BLA on the consolidation of memory for inhibitory avoidance (IA) training. Male Sprague–Dawley rats (≈300 g) were trained on a step‐through IA task and, 48 h later, tested for retention as indexed by their latencies to enter the shock compartment on the test day. Drugs were infused into the BLA or central amygdala nucleus (CEA) immediately or 3 h after training via bilateral cannulae. DA infused into the BLA immediately after training enhanced retention, whereas DA infused into the BLA 3 h after training or into the CEA did not affect retention. Infusions of the dopaminergic antagonist cis‐Flupenthixol together with DA blocked the DA‐induced memory enhancement. Immediate post‐training intra‐BLA infusions of the D1 receptor antagonist SCH 23390 or the D2 receptor antagonist sulpiride impaired retention. β‐adrenergic or muscarinic cholinergic receptor antagonists coinfused into the BLA with DA blocked the memory enhancing effects of DA. These findings indicate that dopaminergic activation within the BLA modulates memory consolidation and that the modulation involves activation of both D1 and D2 receptors and concurrent activation of β‐adrenergic and cholinergic influences within the BLA.
Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis
Authors: Amendola Julien , Verrier Bernard , Roubertoux Pierre , Durand Jacques 
Published: November 2004

AbstractMost neurodegenerative diseases become manifest at an adult age but abnormalities or pathological symptoms appear earlier. It is important to identify the initial mechanisms underlying such progressive neurodegenerative disease in both humans and animals. Transgenic mice expressing the familial amyotrophic lateral sclerosis (ALS)‐linked mutation (G85R) in the enzyme superoxide dismutase 1 (SOD1) develop motor neuron disease at 8–10 months of age. We address the question of whether the mutation has an early impact on spinal motor networks in postnatal mutant mice. Behavioural tests showed a significant delay in righting and hind‐paw grasping responses in mutant SOD1G85R mice during the first postnatal week, suggesting a transient motor deficit compared to wild‐type mice. In addition, extracellular recordings from spinal ventral roots in an in vitro brainstem–spinal cord preparation demonstrated different pharmacologically induced motor activities between the two strains. Rhythmic motor activity was difficult to evoke with N‐methyl‐dl‐aspartate and serotonin at the lumbar levels in SOD1G85R mice. In contrast to lumbar segments, rhythmic activity was similar in the sacral roots from the two strains. These results strongly support the fact that the G85R mutation may have altered lumbar spinal motor systems much earlier than previously recognized.