bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engagement of visual fixation suppresses sensory responsiveness and multisensory integration in the primate superior colliculus
Authors: Bell A. H. , Corneil B. D. , Munoz D. P. , Meredith M. A. 
Published: November 2003

AbstractNeurons in the intermediate and deep layers of the superior colliculus (SC) often exhibit sensory‐related activity in addition to discharging for saccadic eye movements. These two patterns of activity can combine so that modifications of the sensory response can lead to changes in orienting behaviour. Can behavioural factors, however, influence sensory activity? In this study of rhesus monkeys, we isolate one behavioural factor, the state of visual fixation, and examine its influences on sensory processing and multisensory integration in the primate SC. Two interleaved fixation conditions were used: a FIX condition requiring exogenous fixation of a visible fixation point; and a FIX‐BLINK condition, requiring endogenous fixation in the absence of a visible fixation point. Neurons of the SC were influenced by fixation state, exhibiting both lower levels of sensory activity and reduced multisensory interactions when fixation was exogenously engaged on a visible fixation point. These results are consistent with active visual fixation suppressing responses to extraneous stimuli, and thus demonstrate that sensory processing and multisensory responses in the SC are not dependent solely on the physical properties of the sensory environment, but are also dynamically influenced by the behavioural state of the animal.
Dynamics of Ca2+ and Na+ in the dendrites of mouse cerebellar Purkinje cells evoked by parallel fibre stimulation
Authors: Kuruma Akinori , Inoue Takafumi , Mikoshiba Katsuhiko 
Published: November 2003

AbstractCa2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3–50‐times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached ∼100 µm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P‐type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients.
Synaptic and non‐synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activities
Authors: Klueva Julia , Munsch Thomas , Albrecht Doris , Pape Hans‐Christian 
Published: November 2003

AbstractLateral amygdala (LA) activity during synchronized‐epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple‐site extra‐ and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4‐aminopyridine (50 µm) induced epileptiform discharges in all regions under study. Slow interictal‐like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal‐like activity. Disconnection of the amygdala resulted in de‐synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal‐like activity was intracellularly reflected in LA projection neurons as γ‐aminobutyric acid (GABA)A/B receptor‐mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal‐like activity in all areas under study. We conclude that interictal‐like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons.
Modulation of neuronal activity by the endogenous pentapeptide QYNAD
Authors: Meuth Sven G. , Budde Thomas , Duyar Hüseyin , Landgraf Peter , Broicher Tilman , Elbs Martin , Brock Roland , Weller Michael , Weissert Robert , Wiendl Heinz 
Published: November 2003

AbstractInflammation and demyelination both contribute to the neurological deficits characteristic of multiple sclerosis. Neurological dysfunctions are attributable to inflammatory demyelination and, in addition, to soluble factors such as nitric oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in the cerebrospinal fluid of patients with demyelinating disorders, has been proposed to promote axonal dysfunction by blocking sodium channels. The present study aimed at characterizing the properties of QYNAD in acutely isolated thalamic neurons in vitro. QYNAD, but not a scrambled peptide (NYDQA), blocked sodium channels in neurons by shifting the steady‐state inactivation to more negative potentials. Blocking properties followed a dose–response curve with a maximum effect at 10 µm. A fluorescently labelled QYNAD analogue with retained biological activity specifically stained thalamic neurons, positive for type II sodium channels, thus demonstrating the specificity of QYNAD binding. Our study confirms and extends previous observations describing QYNAD as a potent sodium channel‐blocking agent. These data as well as our preliminary observations in in vivo experiments in an animal model of inflammatory CNS demyelination warrant further in vivo studies in order to clarify the exact pathogenetic role of QYNAD in inflammatory neurological diseases.
Correlated stage‐ and subfield‐associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy
Authors: Becker Albert J. , Chen Jian , Zien Alexander , Sochivko Dmitry , Normann Sabine , Schramm Johannes , Elger Christian E. , Wiestler Otmar D. , Blümcke Ingmar 
Published: November 2003

AbstractEpileptic activity evokes profound alterations of hippocampal organization and function. Genomic responses may reflect immediate consequences of excitatory stimulation as well as sustained molecular processes related to neuronal plasticity and structural remodeling. Using oligonucleotide microarrays with 8799 sequences, we determined subregional gene expression profiles in rats subjected to pilocarpine‐induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA;P < 0.05, twofold change,n = 3 per stage). Patterns of gene expression corresponded to distinct stages of epilepsy development. The highest number of differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx. 700 genes) was observed 3 days after status epilepticus. The majority of up‐regulated genes was associated with mechanisms of cellular stress and injury – 14 days after status epilepticus, numerous transcription factors and genes linked to cytoskeletal and synaptic reorganization were differentially expressed and, in the stage of chronic spontaneous seizures, distinct changes were observed in the transcription of genes involved in various neurotransmission pathways and between animals with low vs. high seizure frequency. A number of genes (n = 18) differentially expressed during the chronic epileptic stage showed corresponding expression patterns in hippocampal subfields of patients with pharmacoresistant temporal lobe epilepsy (n = 5 temporal lobe epilepsy patients; U133A microarrays, Affymetrix; covering 22 284 human sequences). These data provide novel insights into the molecular mechanisms of epileptogenesis and seizure‐associated cellular and structural remodeling of the hippocampus.
Pain processing within the primary somatosensory cortex in humans
Authors: Inui Koji , Wang Xiaohong , Qiu Yunhai , Nguyen Binh Thi , Ojima Shiro , Tamura Yohei , Nakata Hiroki , Wasaka Toshiaki , Tran Tuan Diep , Kakigi Ryusuke 
Published: November 2003

AbstractTo investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20‐ and 30‐ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS‐activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.
Single olfactory sensory neurons simultaneously integrate the components of an odour mixture
Authors: Duchamp‐Viret Patricia , Duchamp André , Chaput Michel A. 
Published: November 2003

AbstractMost odours are complex mixtures. However, the capacities of olfactory sensory neurons (OSNs) to process complex odour stimuli have never been explored in air‐breathing vertebrates. To face this issue, the present study compares the electrical responses of single OSNs to two odour molecules, delivered singly and mixed together, in rats in vivo. This work is the first aimed at demonstrating that single OSNs simultaneously integrate several chemical signals and which, furthermore, attempts to describe such processes for the whole concentration range over which single OSNs can work. The results stress that complex interactions occur between components in odour mixtures and that OSN responses to such mixtures are not simply predictable from the responses to their components. Three types of interactions are described. They are termed suppression, hypoadditivity and synergy, in accord with psychophysical terminology. This allows us to draw links between peripheral odour reception and central odour coding. Indeed, events occurring in single OSNs may account for the dominating or even the masking effects of odour molecules in complex mixtures, i.e. for the prevailing action of a minor component in the final qualitative perception of a mixture. We conclude that our observations with binary mixtures anticipate the complexity of processes which may rise at the level of a single OSN in physiological conditions. Following this hypothesis, a natural odour would induce a multi‐chemical integration at the level of single OSNs which may result in refining their individual odour‐coding properties, leading them to play a crucial role in the final performance of the olfactory system.
Seizures preferentially stimulate proliferation of radial glia‐like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis
Authors: Hüttmann Kerstin , Sadgrove Matthew , Wallraff Anke , Hinterkeuser Stefan , Kirchhoff Frank , Steinhäuser Christian , Gray William P. 
Published: November 2003

AbstractKainate‐induced seizures increase hippocampal neurogenesis. Glial fibrillary acidic protein‐positive astrocytes with radial processes in the dentate gyrus share many of the characteristics of radial glia and appear to act as precursor cells for adult dentate neurogenesis. Using the chemoconvulsant kainate and transgenic mice with human glial‐fibrillary acidic protein (hGFAP) promoter‐controlled enhanced green fluorescent protein (EGFP) expression, we examined the proliferation, morphology and electrophysiological properties of astrocytes in the neurogenic subgranular zone of the dentate gyrus in control animals and upon the induction of seizure‐induced cell proliferation, three days post‐kainate. EGFP‐positive cells with and without radial processes could easily be distinguished. Kainate treatment caused a significant increase in the total number of proliferating EGFP‐positive cells, particularly a tenfold elevation in the number of proliferating radial glia‐like astrocytes, and also caused a preferential shift in the dividing cell population towards cells expressing EGFP. Immunohistochemical analysis revealed a surprisingly low proportion of cells coexpressing the astroglial marker S100β and EGFP. Kainate increased the number of EGFP‐positive, S100β‐positive and S100β‐positive–EGFP‐positive astrocytes in the subgranular zone. We also report a subset of faintly EGFP‐positive cells expressing markers of early neuronal differentiation. Patch‐clamp analysis revealed the presence of three functionally different populations of EGFP‐positive cells in both kainate and control tissue. We conclude that there is an early increase in proliferating radial glia‐like astrocytes in the dentate after kainate‐induced seizures, consistent with a recruitment of precursors for seizure‐induced neurogenesis.
Sensorimotor memory and grip force control: does grip force anticipate a self‐produced weight change when drinking with a straw from a cup?
Authors: Nowak Dennis A. , Hermsdörfer Joachim 
Published: November 2003

AbstractWe examined whether self‐generated weight changes are anticipated by adequate grip force adjustments when repeatedly lifting an instrumented manipulandum. Subjects lifted a cup filled with 500 mL of water prior to and following drinking two portions of water with a straw without touching it. One half of the subjects drank from and lifted an uncovered cup receiving constant visual information about its filling level and the other half of the subjects drank from a covered cup without such visual feedback. During the lifts immediately following the drinking procedures, grip force scaling was erroneously programmed for the heavier weight of the preceding lift as was obvious from an inadequately high rate of grip force development. Vision had only a minor influence on the rate of grip force increase. The influence of vision on the scaling of peak grip force was more pronounced. More accurate force scaling was obtained with an increasing number of lifts performed under each weight condition, indicating an ongoing force adjustment process probably based on sensory feedback. We conclude that self‐generation of a change in the weight of an object to be lifted is not, in itself, sufficient to elicit a predictive grip force output. Rather, accurate feedback information associated with the self‐generated weight change is essential to update internal models related to the mechanical object properties. This assumption was confirmed in pilot experiments; when subjects lifted the cup after having poured water from it, they accurately scaled their fingertip force to the self‐produced weight change. Here, direct sensory feedback from the grasping fingers could signal the weight change and update internal models while pouring water from the cup. Our data support the hypothesis that the sensorimotor system planning and processing predictive fingertip force can operate independently of higher‐level cognitive and perceptual systems.
Glial cell line‐derived neurotrophic factor increases calcitonin gene‐related peptide immunoreactivity in sensory and motoneurons in vivo
Authors: Ramer Matt S. , Bradbury Elizabeth J. , Michael Gregory J. , Lever Isobel J. , McMahon Stephen B. 
Published: November 2003

AbstractCalcitonin gene‐related peptide (CGRP) is expressed at high levels in roughly 50% of spinal sensory neurons and plays a role in peripheral vasodilation as well as nociceptive signalling in the spinal cord. Spinal motoneurons express low levels of CGRP; motoneuronal CGRP is thought to be involved in end‐plate plasticity and to have trophic effects on target muscle cells. As both sensory and motoneurons express receptors for glial cell line‐derived neurotrophic factor (GDNF) we sought to determine whether CGRP was regulated by GDNF. Rats were treated intrathecally for 1–3 weeks with recombinant human GDNF or nerve growth factor (NGF) (12 µg/day) and dorsal root ganglia and spinal cords were stained for CGRP. The GDNF treatment not only increased CGRP immunoreactivity in both sensory and motoneurons but also resulted in hypertrophy of both populations. By combined in situ hybridization and immunohistochemistry we found that, in the dorsal root ganglia, CGRP was up‐regulated specifically in neurons expressing GDNF but not NGF receptors following GDNF treatment. Despite the increase in CGRP in GDNF‐treated rats, there was no increase in thermal or mechanical pain sensitivity, while NGF‐treated animals showed significant decreases in pain thresholds. In motoneurons, GDNF increased the overall intensity of CGRP immunoreactivity but did not increase the number of immunopositive cells. As GDNF has been shown to promote the regeneration of both sensory and motor axons, and as CGRP appears to be involved in motoneuronal plasticity, we reason that at least some of the regenerative effects of GDNF are mediated through CGRP up‐regulation.
Specific γ‐hydroxybutyrate‐binding sites but loss of pharmacological effects of γ‐hydroxybutyrate in GABAB(1)‐deficient mice
Authors: Kaupmann Klemens , Cryan John F. , Wellendorph Petrine , Mombereau Cedric , Sansig Gilles , Klebs Klaus , Schmutz Markus , Froestl Wolfgang , Van Der Putten Herman , Mosbacher Johannes , Bräuner‐Osborne Hans , Waldmeier Peter , Bettler Bernhard 
Published: November 2003

Abstractγ‐Hydroxybutyrate (GHB), a metabolite of γ‐aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. γ‐Hydroxybutyrate and its prodrug, γ‐butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high‐affinity [3H]GHB‐binding sites coupled to G‐proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)−/− mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB‐binding sites in brains of GABAB(1)−/− and wild‐type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9‐tetrahydro‐5‐hydroxy‐5H‐benzocyclohept‐6‐ylidene acetic acid (NCS‐382) appear unchanged in GABAB(1)−/− compared with wild‐type mice, demonstrating that GHB‐ are distinct from GABAB‐binding sites. In the presence of the GABAB receptor positive modulator 2,6‐di‐tert‐butyl‐4‐(3‐hydroxy‐2,2‐dimethyl‐propyl)‐phenol GHB induced functional GTPγ[35S] responses in brain membrane preparations from wild‐type but not GABAB(1)−/− mice. The GTPγ[35S] responses in wild‐type mice were blocked by the GABAB antagonist [3‐[[1‐(S)‐(3,4dichlorophenyl)ethyl]amino]‐2‐(S)‐hydroxy‐propyl]‐cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS‐382. Altogether, these findings suggest that the GHB‐induced GTPγ[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)−/− mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta‐wave induction seen in wild‐type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB‐binding sites remain elusive.
Inhibitory effect of mouse neocortex layer I on the underlying cellular network
Authors: Shlosberg Dan , Patrick Saundra L. , Buskila Yossi , Amitai Yael 
Published: November 2003

AbstractThe mammalian cortical layer I is a convergence site for axons of sub‐ and intracortical origin, and the apical dendritic tufts of pyramidal neurons. A prominent feature of layer I is an extensive plexus of inhibitory axons, which originate from stellate cells in all cortical laminae. The role of this inhibitory projection in the activity of cortical networks has yet to be determined. We investigated the degree to which inhibitory inputs within layer I affect the activity of the underlying cellular network. Field potentials (FPs) were recorded in layer II/III. Focal application of the GABAA blocker picrotoxin in layer I above the recording pipette or the removal of layer I resulted in larger FP amplitudes for stimulations at control‐equal intensities. When inhibition was partially blocked, the removal of layer I caused a significant reduction in the threshold stimulus intensity required for generating epileptiform events, and a rise in the propagation velocity of these events. Immunocytochemistry for chemical markers of interneurons proved that the inhibitory input to layer I is predominantly somatostatin immunoreactive (SM‐ir), such that layer I contains approximately one‐third of all SM‐ir axons in the cortex. Calretinin‐immunoreactive axons were also present in layer I at a lower density. We conclude that the impact of layer I on the cortical cellular network includes a significant inhibitory component. This inhibition confers a moderate restraining influence, and its removal increases the excitability of cortical circuits, but not sufficiently to induce epileptic phenomena.