bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple‐site optical recording for characterization of functional synaptic organization of the optic tectum of rainbow trout
Authors: Kinoshita Masae , Ueda Risa , Kojima Satoshi , Sato Katsushige , Watanabe Masahiko , Urano Akihisa , Ito Etsuro 
Published: March 2003

AbstractTo map the functional synaptic organization over a wide area in the optic tectum, we directly monitored two‐dimensional propagation of postsynaptic depolarization evoked by firing of retinotectal afferents in optic tectum slices prepared from rainbow trout (Oncorhynchus mykiss), using a voltage‐sensitive dye and a photodiode array system. The postsynaptic responses to afferent stimulation first propagated in the stratum opticum and stratum fibrosum et griseum superficiale in an anterograde fashion in the afferents and then expanded vertically into the deep layers. This vertical propagation appeared to occur along a bundle‐like structure that corresponded well with a cluster of neurons whose somata are located in the stratum periventriculare. Pharmacological studies showed that these postsynaptic responses were mediated by ionotropic glutamate receptors. On the other hand, the optical signals appeared to consist of at least two components (a transient signal and a slow signal). The second transient signal summated with the first slow signal by paired stimulation, suggesting that the transient and slow signals originated from different cell types. Taken together, these results showed that the functional synaptic organization of the teleost optic tectum comprises of two depolarization‐signal propagating paths along a horizontal layer structure and a vertical bundle‐like structure and that these synaptic responses occur via glutamatergic transmission.
Adaptive loss of ultraviolet‐sensitive/violet‐sensitive (UVS/VS) cone opsin in the blind mole rat (Spalax ehrenbergi)
Authors: David‐Gray Z. K. , Bellingham J. , Munoz M. , Avivi A. , Nevo E. , Foster R. G. 
Published: March 2003

AbstractIn previous studies, fully functional rod and long‐wavelength‐sensitive (LWS) cone photopigments have been isolated from the eye of the subterranean blind mole rat (Spalax ehrenbergisuperspecies).Spalaxpossesses subcutaneous atrophied eyes and lacks any ability to respond to visual images. By contrast this animal retains the ability to entrain circadian rhythms of locomotor behaviour to environmental light cues. As this is the only known function of the eye, the rod and LWS photopigments are thought to mediate this response. Most mammals are dichromats possessing, in addition to a single rod photopigment, two classes of cone photopigment, LWS and ultraviolet‐sensitive/violet‐sensitive (UVS/VS) with differing spectral sensitivities which mediate colour vision. In this paper we explore whetherSpalaxis a dichromat and has the potential to use colour discrimination for photoentrainment. Using immunocytochemistry and molecular approaches we demonstrate thatSpalaxis a LWS monochromat.Spalaxlacks a functional UVS/VS cone photopigment due to the accumulation of several deleterious mutational changes that have rendered the gene nonfunctional. Using phylogenetic analysis we show that the loss of this class of photoreceptor is likely to have arisen from the visual ecology of this species, and is not an artefact of having an ancestor which lacked a functional UVS/VS cone photopigment. We conclude that colour discrimination is not a prerequisite for photoentrainment in this species.
Simultaneous intracerebral EEG recordings of early auditory thalamic and cortical activity in human
Authors: Yvert Blaise , Fischer Catherine , Guénot Marc , Krolak‐Salmon Pierre , Isnard Jean , Pernier Jacques 
Published: March 2003

AbstractWe describe documented simultaneous intracerebral auditory evoked potentials from the auditory cortex and medial geniculate body (MGB) of a human patient. The MGB response lasted > 300 ms, with an initial negativity at 13.5 ms (N13), two positive peaks P21 and P29, and two broader negativities N50 and N200. P21 and N50 amplitudes were strongest for lowest tone frequencies, suggesting possible MGB tonotopic organization. Thalamic peaks were strongly interlaced with cortical activities recorded in Heschl's gyri before 30 ms: N13 preceded the first cortical component by 3.5 ms, then P21 and P29 preceded and lagged, respectively, the following two cortical polarity reversals by 1.5–2 ms. This study provides new functional data on the human MGB, and supports a more complex than simply relay‐like role of the thalamus in sound perception.
GABAergic and glycinergic synapses onto neurokinin‐1 receptor‐immunoreactive neurons in the pre‐Bötzinger complex of rats: light and electron microscopic studies
Authors: Liu Ying‐Ying , Wong‐Riley Margaret T. T. , Liu Jin‐Ping , Jia Yi , Liu Hui‐Ling , Jiao Xi‐Ying , Ju And Gong 
Published: March 2003

AbstractThe pre‐Bötzinger complex (preBötC) in the ventrolateral medulla is thought to be the kernel for respiratory rhythm generation. Neurons in the preBötC contain intense neurokinin‐1 receptor (NK1R) immunoreactivity. Some of these neurons in the adult preBötC are presumed to be the pre‐inspiratory interneurons that are essential for generating respiratory rhythm in the neonate. Chloride‐mediated synaptic inhibition is critical for rhythmogenesis in the adult. The present study used immunofluorescence histochemistry and immunogold‐silver staining to determine the inhibitory synaptic relationship between glutamic acid decarboxylase (GAD)‐ or glycine transporter 2 (GlyT2)‐immunoreactive (ir) boutons and NK1R‐ir neurons in the preBötC of adult rats. Under the confocal microscope, we found that GAD‐ and GlyT2‐ir boutons were in close apposition to NK1R‐ir somas and dendrites in the preBötC. Under the electron microscope, GAD‐ and GlyT2‐ir terminals were in close apposition to NK1R‐ir somas and dendrites. Symmetric synapses were identified between GAD‐ or GlyT2‐ir terminals and NK1R‐ir neurons. A total of 51.6% GAD‐ir and 38.2% GlyT2‐ir terminals were found to contact or make synapses with NK1R‐ir profiles, respectively. GAD‐ and GlyT2‐ir terminals synapsed not only upon NK1R‐ir neurons but also upon NK1R immuno‐negative neurons. NK1R‐ir neurons received both symmetric (presumed inhibitory) and asymmetric (presumed excitatory) synapses. Thus, the present findings provide the morphological basis for inhibitory inputs to NK1R‐ir neurons in the preBötC, consistent with the suggestion that chloride‐mediated synaptic inhibition may contribute importantly to rhythm generation by controlling the membrane potential trajectory and resetting rhythmic bursting of the kernel neurons in the adult.
Flicker in the visual background impairs the ability to process a moving visual stimulus
Authors: Churan Jan , Ilg Uwe J. 
Published: March 2003

AbstractFor the detection of a moving object, segregating the object from the background is a necessary first step. This segregation can be achieved by detection of differences in the spatial, temporal and spatio‐temporal properties of the object and background. Here we investigate how flicker influences the perception of a moving object in man and monkey, and we examine the neuronal responses in extrastriate medial temporal and medial superior temporal areas (MT and MST) of two rhesus monkeys. The performance of humans and monkeys in a direction discrimination task was impaired in the presence of flicker in the background compared to the static background condition. A similar effect was found in recordings from 155 single units in areas MT and MST during the discrimination task. The discriminability (d′) of the neuronal responses in preferred and nonpreferred directions was reduced by 33% on average in the presence of a flicker background compared to the static background. This reduction in discriminability was not caused by differences in variance of the neuronal activity for the two background conditions, but was due to a reduction of the difference between the activities in preferred and nonpreferred direction. This reduction in directional selectivity could be traced back to two different mechanisms: in 32 out of 155 neurons (21%), the decrease resulted from an increase in the response to the stimulus moving in the nonpreferred direction; in 62 out of 155 neurons (40%), the reduction in directional selectivity was due to a decrease in the response to the preferred direction. These results give deeper insights into how moving stimuli are processed in the presence of background flicker as present in natural visual scenes.
Change in bi‐directional plasticity at CA1 synapses in hippocampal slices taken from 6‐hydroxydopamine‐treated rats: the role of endogenous norepinephrine
Authors: Yang Hsiu‐Wen , Lin Yi‐Wen , Yen Chia‐De , Min Ming‐Yuan 
Published: March 2003

AbstractThe object of the present study is to investigate the role of endogenous adrenergic innervation in regulating bi‐directional synaptic plasticity in rat hippocampal CA1 synapses. The endogenous adrenergic system was eliminated by giving subcutaneous injection of 6‐hydroxydopamine (6‐OHDA) to rats immediately after birth, and the animals were killed for experiments at postnatal ages of 25–35 days. In hippocampal slices taken from 6‐OHDA‐treated animals, theta‐burst stimulation at 100 Hz failed to induce long‐term potentiation (LTP) at CA1 synapses. However, the induction of long‐term depression (LTD) by prolonged low frequency stimulation at 1 Hz was unaffected in slices from 6‐OHDA‐treated animals. Bath application of norepinephrine (NE) restored LTP to control levels and blocked LTD. This effect was mimicked by β‐ but not α‐adrenergic receptor agonists, i.e. by isoproterenol but not phenylephrine. The activators of adenylyl cyclase and protein kinase A (PKA), i.e. forskolin and 8‐bromoadenosine‐3′, 5′‐cyclic monophosphate, respectively, restored LTP in slices from 6‐OHDA‐treated animals. In addition, application of the D1/D5 receptor agonist, dihydrexidine, also restored LTP in slices from 6‐OHDA‐treated animals. These results suggest that physiologically the recruitment of catecholamine innervation may be important for induction of LTP at hippocampal CA1 synapses during tetanic stimulation, while it may not be essential for LTD induction by prolonged 1 Hz stimulation. The released NE and dopamine exert their role in modulating synaptic plasticity via activation of β‐adrenergic and D1/D5 receptors, respectively, which in turn increase the levels of cytoplasm adenosine‐3′,5′‐cyclic monophosphate and PKA.
Ephrin‐B3–EphA4 interactions regulate the growth of specific thalamocortical axon populations in vitro
Authors: Takemoto Makoto , Fukuda Tsuyoshi , Sonoda Rie , Murakami Fujio , Tanaka Hideaki , Yamamoto Nobuhiko 
Published: March 2003

AbstractThe role was studied of ephrin‐B3, a ligand of the Eph family of tyrosine kinase receptors, in the formation of cortical connectivity. In situ hybridization and immunohistochemistry showed that EphA4, a receptor of ephrin‐B3, was expressed in the lateral thalamus (visual and somaotosensory thalamus) of the developing rat brain, but not in the medial thalamic nuclei which project to the limbic cortex. Correspondingly, ephrin‐B3 was expressed strongly in the developing limbic cortex including amygdala, entorhinal cortex and hippocampus. To examine the action of ephrin‐B3 on thalamic axons, either lateral or medial thalamic explants were cultured on membranes obtained from ephrin‐B3‐expressing COS cells. Axonal growth was inhibited for cells from the lateral thalamus but not from the medial thalamus. These results suggest that ephrin‐B3 contributes to regional specificity by suppressing axonal growth of lateral thalamic neurons.
Chronic nicotine treatment changes the axonal distribution of 68 kDa neurofilaments in the rat ventral tegmental area
Authors: Sbarbati Andrea , Bunnemann Bernd , Cristofori Patrizia , Terron Andrea , Chiamulera Christian , Merigo Flavia , Benati Donatella , Bernardi Paolo , Osculati Francesco 
Published: March 2003

AbstractRegion‐specific decreases of neurofilament proteins (NF) were described in the ventral tegmental area (VTA) of rats treated chronically with morphine, cocaine or alcohol. In a previous study, we demonstrated that NF levels were also changed in the VTA after chronic treatment with nicotine. The aim of this study was to clarify the submicroscopic basis of decreased immunoreactivity for NF‐68, NF‐160 and NF‐200, as determined by using NR4, BF10 and RT97 antibodies, respectively. Microdensitometric analysis of brain sections showed that immunoreactivity for all NF was reduced in the VTA of animals exposed chronically to nicotine (0.4 mg/kg per day, 6 days of treatment), when compared to rats exposed to saline. Reduction in immunoreactivity was significant for NF‐68 (P < 0.05), NF‐160 (P < 0.01) and NF‐200 (P < 0.05), showing a relative reduction of 34%, 42% and 38%, respectively, when compared to saline‐treated rats. No difference was observed for any of the NF under study when immunoreactivity measurements in the substantia nigra were compared. Ultrastructural analysis was applied to evaluate changes in NF‐68, NF‐160 and NF‐200 immunoreactivity in regions of the VTA that contain dopaminergic neurons following chronic nicotine treatment. At the electron microscopic level, no degenerative changes were found in neurons or glial cells of the VTA. With ultrastructural immunohistochemistry, evaluation of the homogeneity parameter of NF distribution showed a loss of homogeneity for NF‐68 linked to the nicotine treatment. In areas in which NF organization appeared well preserved, analysis of the numerical density of NF revealed no significant difference for NF‐68 (897/µm2 vs. 990/µm2), NF‐160 (970/µm2 vs. 820/µm2) and NF‐200 (1107/µm2 vs. 905/µm2) in nicotine‐treated rats when compared to saline‐treated rats. These results confirm that nicotine shares the same properties with cocaine and morphine in reducing NF in the VTA, a key brain structure of the rewards system, and that chronic nicotine treatment changes the axonal distribution of 68 kDa neurofilaments in the rat VTA.
Multiple determinants in voltage‐dependent P/Q calcium channels control their retention in the endoplasmic reticulum
Authors: Cornet Véronique , Bichet Delphine , Sandoz Guillaume , Marty Isabelle , Brocard Jacques , Bourinet Emmanuel , Mori Yasuo , Villaz Michel , De Waard Michel 
Published: March 2003

AbstractSurface expression level of voltage‐dependent calcium channels is tightly controlled in neurons to avoid the resulting cell toxicity generally associated with excessive calcium entry. Cell surface expression of high voltage‐activated calcium channels requires the association of the pore‐forming subunit, Cavα, with the auxiliary subunit, Cavβ. In the absence of this auxiliary subunit, Cavα is retained in the endoplasmic reticulum (ER) through mechanisms that are still poorly understood. Here, we have investigated, by a quantitative method based on the use of CD8α chimeras, the molecular determinants of Cavα2.1 that are responsible for the retention, in the absence of auxiliary subunits, of P/Q calcium channels in the ER (referred to here as ‘ER retention’). This study demonstrates that the I–II loop of Cavα2.1 contains multiple ER‐retention determinants beside the β subunit association domain. In addition, the I–II loop is not the sole domain of calcium channel retention as two regions identified for their ability to interact with the I–II loop, the N‐ and C‐termini of Cavα2.1, also produce ER retention. It is also not an obligatory determinant as, similarly to low‐threshold calcium channels, the I–II loop of Cavα1.1 does not produce ER retention in COS7 cells. The data presented here suggests that ER retention is suppressed by sequential molecular events that include: (i) a correct folding of Cavα in order to mask several internal ER‐retention determinants and (ii) the association of other proteins, including the Cavβ subunit, to suppress the remaining ER‐retention determinants.
The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation
Authors: Zhang Yumin , Rosenberg Paul A. 
Published: March 2003

AbstractPyrroloquinoline quinone (PQQ) is a redox active essential nutrient that can generate or scavenge superoxide depending on its microenvironment. PQQ has been shown previously to be neuroprotective in a rodent stroke model. Here we test whether PQQ interacts with reactive nitrogen species, known to be involved in the pathogenesis of stroke. Using rat forebrain neurons in culture, we determined that the toxicity of SIN‐1 was mediated by peroxynitrite and that PQQ could block this toxic action. However, PQQ could not block the toxicity of peroxynitrite itself. Both SIN‐1 and peroxynitrite caused ATP depletion, but only SIN‐1 evoked ATP depletion was blocked by PQQ. In a cell‐free system, PQQ blocked nitration of bovine serum albumin produced by SIN‐1, but potentiated peroxynitrite‐induced nitration. PQQ was unable to block ATP depletion and cell death induced by NO· donors (DEA/NO, DPT/NO and DETA/NO), indicating that it does not directly interact with nitric oxide, and suggesting that it acts as a superoxide scavenger. PQQ significantly potentiated cGMP accumulation evoked by SIN‐1, similar to the effect of superoxide dismutase (SOD). However, unlike SOD, which potentiated neurotoxicity induced by SIN‐1, PQQ blocked its toxicity, arguing against the possibility that PQQ functions simply as a SOD mimetic. Indeed, substantially less H2O2 was produced by the incubation of SIN‐1 with PQQ, when compared to SOD. These results suggest that PQQ scavenges superoxide without forming toxic levels of H2O2. Therefore, the protective effect of PQQ on stroke might be due, at least in part, to the suppression of peroxynitrite formation.
Potentiation of inhibitory glycinergic neurotransmission by Zn2+: a synergistic interplay between presynaptic P2X2 and postsynaptic glycine receptors
Authors: Laube Bodo 
Published: March 2003

AbstractThe divalent cation zinc is known to modulate chloride currents carried by native and recombinant mammalian glycine receptors (GlyRs). To unravel the effect of Zn2+ on glycinergic neurotransmission, inhibitory postsynaptic currents (IPSC) of rat spinal neurons grown in culture were analysed in the absence and presence of Zn2+. Low concentrations of Zn2+ (0.5 and 5 µm) augmented the mean amplitude of miniature IPSCs by ≈ 40% over values obtained in the absence of zinc, whereas higher concentrations of Zn2+ (50 µm) significantly decreased mean amplitude values. Remarkably, low concentrations of Zn2+ also significantly increased the mean frequency of miniature IPSCs. This effect was blocked by the P2X receptor antagonists PPADS and suramin, indicating the presence of Zn2+‐sensitive presynaptic P2X receptors on glycinergic terminals. Immunostaining with antibodies against different P2X receptor subtypes revealed that P2X2 receptors partially colocalize with the GlyR. Potentiating concentrations of Zn2+ also affected the kinetics of miniature and evoked IPSCs by significantly prolonging their decay time constants. Electrophysiological analysis of heterologously expressed glycine transporters (GlyT) revealed for GlyT2 zero, and for GlyT1 a modest (< 20%), reduction of glycine uptake in the presence of 5 µm Zn2+, indicating that prolongation of glycinergic IPSCs by Zn2+ is not due to inhibition of glycine removal from the synaptic cleft. Together, these results suggest that Zn2+ is a potent modulator of glycinergic synaptic transmission which increases in a synergistic manner the agonist affinity of both presynaptic P2X2 receptors and postsynaptic GlyRs.
Characterization of large conductance Ca2+‐activated K+ channels in cerebellar Purkinje neurons
Authors: Womack Mary D. , Khodakhah Kamran 
Published: March 2003

AbstractWe investigated the role of large conductance, calcium‐activated potassium channels (BK channels) in regulation of the excitability of cerebellar Purkinje neurons. Block of BK channels by iberiotoxin reduced the afterhyperpolarization of spontaneous action potentials in Purkinje neurons in acutely prepared cerebellar slices. To establish the conditions required for activation of BK channels in Purkinje neurons, the dependence of BK channel open probability on calcium concentration and membrane voltage were investigated in excised patches from soma of acutely prepared Purkinje cells. Single channel currents were studied under conditions designed to select for potassium currents and in which voltage‐activated currents were largely inactivated. Micromolar calcium concentrations activated channels with a mean single channel conductance of 266 pS. BK channels were activated by both calcium and membrane depolarization, and showed no sign of inactivation. At a given calcium concentration, depolarization over a 60‐mV range increased the mean open probability (PO) from < 0.1 to > 0.8. Increasing the calcium concentration shifted the voltage required for half maximal activation to more hyperpolarized potentials. The apparent affinity of the channels for calcium increased with depolarization. At −60 mV the apparent affinity was ≈35 µm decreasing to ≈3 µM at +40 mV. These results suggest that BK channels are unlikely to be activated at resting membrane potentials and calcium concentrations. We tested the hypothesis that Purkinje cell BK channels may be activated by calcium entry during individual action potentials. Significant BK channel activation could be detected when brief action potential‐like depolarizations were applied to patches under conditions in which the sole source of calcium was flux across the plasma membrane via the endogenous voltage‐gated calcium channels. It is proposed that BK channels regulate the excitability of Purkinje cells by contributing to afterhyperpolarizations and perhaps by shaping individual action potentials.
Glucocorticoids alter calcium conductances and calcium channel subunit expression in basolateral amygdala neurons
Authors: Karst Henk , Nair Suresh , Velzing Els , Rumpff‐van Essen Lisette , Slagter Eelco , Shinnick‐Gallagher Patricia , Joëls Marian 
Published: March 2003

AbstractGlucocorticoid hormones, which are released in high amounts after stress, enter the brain where they bind to intracellular receptors that are abundant in limbic areas, in particular the hippocampus and amygdala nuclei. Behavioural studies indicate that glucocorticoids modulate learning and memory processes via receptors in the hippocampus and amygdala. So far, the effects of glucocorticoids on amygdala neurons have not been investigated at the cellular and molecular level. We report here that in vitro application of glucocorticoids for 20 min increases 1–4 h later the amplitude of sustained, high‐voltage‐activated calcium currents in principal neurons of the basolateral amygdala. In contrast, the transient, low‐voltage‐activated currents were decreased. We examined whether these functional changes in calcium conductance were accompanied by transcriptional regulation of calcium channel subunits. Analysis of the RNA – collected after recording and then linearly amplified – revealed that glucocorticoid‐mediated increases in sustained calcium currents are associated with a parallel shift in the relative expression of the α1 subunit constituting the pore of the sustained, high‐voltage‐activated (L‐type) calcium channel. These data indicate that glucocorticoids, probably by selectively targeting genes encoding calcium channel subunits, largely alter the calcium influx into basolateral amygdala neurons. These actions could modify amygdala network function and thus contribute to the behavioural effects exerted by the stress hormones via the basolateral amygdala.