bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature and PMA affect different phases of exocytosis in bovine chromaffin cells
Authors: Gil Anabel , Viniegra Salvador , Gutiérrez Luis M. 
Published: March 2003

AbstractAmperometry was used to study secretory kinetics of single bovine chromaffin cells stimulated by transient depolarizations at different temperatures. The initial rate of release was moderately enhanced when the temperature was raised from 18 to 22 and 37 °C. Secretion increased drastically at a later period, 5–10 s after the initiation of stimulus. Interestingly, incubation of the cells with phorbol 12‐myristate 13‐acetate (PMA) clearly enhanced fast secretory components. In addition, the rate of secretion of the slower component recruited by prolonged depolarizations (t > 30 s) was unaffected at the range of temperatures normally used in secretory experiments (22–37 °C). A ‘counting events’ analysis of secretion, which avoids the influence of event charge changes, showed specific increases in a population of vesicles fusing between 7 and 12 s over the same range of temperatures, and a marked increase in vesicles fusing during the initial phase (1–5 s), of PMA‐treated cell secretion. An analysis of temperature influence on transient components released by high sucrose, the secretion elicited by cell permeabilization with digitonin, and studies of the individual characteristics of amperometric events, allow us to conclude that an increase in the size of a secondary‐released vesicle population is the main factor contributing to temperature‐dependent enhancement of secretion, in clear contrast to the enhancement of fast releasable pools caused by phorbol esters.
Corticotropin‐releasing factor triggers neurite outgrowth of a catecholaminergic immortalized neuron via cAMP and MAP kinase signalling pathways
Authors: Cibelli Giuseppe , Corsi Patriza , Diana Gennaro , Vitiello Francesco , Thiel Gerald 
Published: March 2003

AbstractCorticotropin‐releasing factor (CRF), a neuropeptide of 41 amino acids, acts as the major physiological regulator of the basal and stress‐induced release of corticotropin (ACTH), β‐endorphin and other proopiomelanocortin‐derived peptides from the anterior pituitary gland. In addition to its endocrine activity, CRF displays extrahypophysiotropic effects, mainly as a regulator of stress responses. We show here that CRF may additionally function as a differentiating factor in immortalized noradrenergic neuronal CATH.a cells that express CRF receptor type I and resemble locus coeruleus‐derived neurons. CRF triggers morphological changes in CATH.a cells including the appearence of extended long, slender neurites with prominent growth cones. CRF‐treated CATH.a cells exhibit a morphology similar to locus coeruleus neurons in primary culture. CRF‐induced neurite outgrowth of CATH.a cells was blocked by addition of inhibitors for cAMP‐dependent protein kinase or extracellular signal‐regulated protein kinase (ERK), a subtype of the mitogen‐activated protein kinases. The participation of ERK within the CRF signalling cascade was further confirmed by Western blot experiments, with antibodies directed against the phosphorylated form of ERK, and also with transcription‐based assays. We conclude that CRF functions as a differentiating factor of CATH.a cells via the cAMP and the MAP kinase signalling pathways.
Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose‐dependent manner
Authors: Nagano Seiichi , Satoh Masahiko , Sumi Hisae , Fujimura Harutoshi , Tohyama Chiharu , Yanagihara Takehiko , Sakoda Saburo 
Published: March 2003

AbstractWe previously reported that abnormal copper release from mutated Cu, Zn‐superoxide dismutase (SOD1) proteins might be a common toxic gain‐of‐function in the pathogenesis of familial amyotrophic lateral sclerosis (FALS) [Ogawa et al. (1997) Biochem. Biophys. Res. Commun., 241, 251–257.]. In the present study, we first examined metallothioneins (MTs), known to bind copper ions and decrease oxidative toxicity, and found a twofold increase in MTs in the spinal cord of the SOD1 transgenic mice with a FALS‐linked mutation (G93A), but not in the spinal cord of wild‐type SOD1 transgenic mice. We then investigated whether the clinical course of FALS mice could be modified by the reduced expression of MTs, by crossing the FALS mice with MT‐I‐ and MT‐II‐deficient mice. FALS mice clearly reached the onset of clinical signs and death significantly earlier in response to the reduction of protein expression. These results indicated that the copper‐mediated free radical generation derived from mutant SOD1 might be related to the degeneration of motor neurons in FALS and that MTs might play a protective role against the expression of the disease.
Perinatal changes of Ih in phrenic motoneurons
Authors: Di Pasquale Eric , Tell Fabien , Ptak Krzysztof , Monteau Roger , Hilaire Gérard 
Published: March 2003

AbstractThe hyperpolarization‐activated cationic current (Ih) was characterized and its maturation studied on phrenic motoneurons (PMNs), from reduced preparations of foetal (E18 and E21) and newborn (P0–P3) rats, using the whole‐cell patch‐clamp technique. In voltage‐clamp mode, 2‐s hyperpolarizing steps (5‐mV, −50 to −110 mV) elicited a noninactivating inward current, blocked by external application of Cs+ or ZD 7288. At −110 mV, Ih current density averaged 0.67 ± 0.41 pA/pF at E18, reached a transient peak at E21 (1.38 ± 0.11 pA/pF) and decreased at P0–P3 (0.77 ± 0.22 pA/pF). V1/2 was similar at E18 and E21 (−79 mV) but was significantly hyperpolarized at P0–P3 (−90 mV). The time constant of activation was voltage‐dependent, and significantly faster at E21. Reversal potential was similar at all ages when estimated by extrapolation or tail current procedures. It was positively shifted by 25 ± 6 mV when external potassium was raised from 3 to 10 mm, suggesting a similar sensitivity to K+ from E18 to P0–3. Cs+ or ZD 7288 applications on PMNs at rest in current‐clamp mode, in a partitioned chamber, induced a 10 ± 2 mV hyperpolarization at E18 and E21, and an 8 ± 2 mV hyperpolarization at P0–3. The area of the central respiratory drive potential or current was increased by 33 and 31%, respectively, at E21, but was not significantly modified at E18 and P0–3. Our data suggest a critical period during the perinatal maturation of Ih during which it is transiently upregulated and attenuates the influence of the central respiratory drive on PMNs just prior to birth.
Spontaneous GABAergic postsynaptic currents in Cajal–Retzius cells in neonatal rat cerebral cortex
Authors: Kilb Werner , Luhmann Heiko J. 
Published: March 2003

AbstractCajal–Retzius cells are among the first neurons appearing during corticogenesis, and play an important role in the establishment of cortical lamination. The variety of neurotransmitter receptors recently found on these cells imply that they are integrated in the neonatal cortical network. To investigate the presence and properties of spontaneous synaptic activity we performed whole‐cell patch‐clamp recordings from visually identified and biocytin‐labelled Cajal–Retzius cells in a tangential slice preparation of neonatal rat cerebral cortex (postnatal days P0–P5). Spontaneous postsynaptic currents (sPSCs) could be observed in about 23% of the cells using a pipette solution containing 136 mm Cl–. The sPSCs occurred at a low frequency (0.07 ± 0.07 Hz, n = 42 cells), had an average amplitude of 24.3 ± 12.4 pA (n = 415 events) and could not be divided in subpopulations according to their amplitude distribution or kinetic properties. The sPSCs were blocked by the GABAA antagonist bicuculline (100 µm), while the glutamatergic antagonists (±)‐2‐amino‐5‐phosphonopentatonic acid (APV, 30 µm) and 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 10 µm), as well as tetrodotoxin (1–2 µm), a blocker of voltage‐gated sodium‐currents, had no significant effect on sPSCs. The incidence rate of sPSCs declined within the age of the rats and no sPSCs could be observed after P4. These results suggest that Cajal–Retzius cells transiently receive action potential‐independent and GABAA receptor‐mediated spontaneous synaptic input, which may contribute to the refinement of cortical circuits.
Signals from cone photoreceptors to L‐type horizontal cells are differentially modulated by low calcium in carp retina
Authors: Xu Hong‐Ping , Luo Dong‐Gen , Yang Xiong‐Li 
Published: March 2003

AbstractCa2+ plays crucial roles in both phototransduction and calcium‐dependent glutamate release from the photoreceptor terminal. Modulation, by lowering extracellular Ca2+, of red‐sensitive (R‐) and short wavelength‐sensitive (S‐) cone‐driven light responses of L‐type horizontal cells (LHCs) was studied in the isolated superfused carp retina using intracellular recording techniques. Low Ca2+ (nominally Ca2+‐free) Ringer's reduced responses of LHCs to both green (500 nm) and red (680 nm) flashes in darkness, with the former being suppressed more substantially than the latter. This differential suppression became more significant when contribution of R‐cones to the green‐light‐induced responses was diminished by a moderate red (680 nm) background light. Application of IBMX, an inhibitor of phosphodiesterase (PDE), increased LHC responses to both red and green flashes equally, resembling the effect of low Ca2+ on phototransduction. In addition, photopic electroretinographic P III responses, reflecting the activity of cones, to red flashes were more potentiated by low Ca2+, compared to those to green flashes, whilst they were both equally potentiated by IBMX. Furthermore, low Ca2+ caused a more pronounced suppression of LHC responses to red flashes than those to green flashes in the presence of IBMX. It is postulated that reduction of LHC responses in low Ca2+ may be due to the ‘saturation suppression’ caused by the increased glutamate release from the photoreceptor terminal and the differential modulation may reflect a consequence of the dual action of low Ca2+ on the PDE activity in the photoreceptor outer segment and the synaptic strength between cones and LHCs.
PSA‐NCAM modulates BDNF‐dependent survival and differentiation of cortical neurons
Authors: Vutskits L. , Djebbara‐Hannas Z. , Zhang H. , Paccaud J.‐P. , Durbec P. , Rougon G. , Muller D. , Kiss J. Z. 
Published: March 2003

AbstractWe show that the loss or inactivation of the polysialic acid (PSA) tail of neural cell adhesion molecule (NCAM) on rat cortical neurons in culture leads to reduced differentiation and survival. The mechanism by which this negative effect is mediated appears to involve the neuronal response to brain‐derived neurotrophic factor (BDNF): (i) in the absence of PSA or in the presence of excess free PSA added to the culture medium, BDNF‐induced cell signalling is reduced; (ii) the addition of exogenous BDNF to the medium reverses the effect of PSA loss or inactivation. These data suggest that PSA‐NCAM, previously shown to modulate cell migration and plasticity, is needed for an adequate sensitivity of neurons to BDNF.
NMDA‐evoked calcium transients and currents in the suprachiasmatic nucleus: gating by the circadian system
Authors: Colwell Christopher S. 
Published: March 2003

AbstractA variety of evidence suggests that the effects of light on the mammalian circadian system are mediated by glutamatergic mechanisms and that the N‐methyl‐d‐aspartate (NMDA) receptor plays an important role in this regulation. One of the fundamental features of circadian oscillators is that their response to environmental stimulation varies depending on the phase of the daily cycle when the stimuli are applied. For example, the same light treatment, which can produce phase shifts of the oscillator when applied during subjective night, has no effect when applied during the subjective day in animals held in constant darkness (DD). We examined the hypothesis that the effects of NMDA on neurons in the suprachiasmatic nucleus (SCN) also vary from day to night. Optical techniques were utilized to estimate NMDA‐induced calcium (Ca2+) changes in SCN cells. The resulting data indicate that there was a daily rhythm in the magnitude and duration of NMDA‐induced Ca2+ transients. The phase of this rhythm was determined by the light–dark cycle to which the rats were exposed with the Ca2+ transients peaking during the night. This rhythm continued when animals were held in DD. γ‐Aminobutyric acid (GABA)ergic mechanisms modulated the NMDA response but were not responsible for the rhythm. Finally, there was a rhythm in NMDA‐evoked currents in SCN neurons that also peaked during the night. This study provides the first evidence for a circadian oscillation in NMDA‐evoked Ca2+ transients in SCN cells. This rhythm may play an important role in determining the periodic sensitivity of the circadian systems response to light.
SB‐334867, a selective orexin‐1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin‐A in rats
Authors: Rodgers R. J. , Halford J. C. G. , Nunes de Souza R. L. , Canto de Souza A. L. , Piper D. C. , Arch J. R. S. , Upton N. , Porter R. A. , Johns A. , Blundell J. E. 
Published: March 2003

AbstractIntracerebroventricular (i.c.v.) administration of the novel hypothalamic neuropeptide orexin‐A stimulates food intake in rats, and delays the onset of behavioural satiety (i.e. the natural transition from feeding to resting). Furthermore, preliminary findings with the selective orexin‐1 receptor antagonist, SB‐334867, suggest that orexin‐A regulation of food intake is mediated via the orexin‐1 receptor. At present, however, little is known about either the intrinsic effects of SB‐334867 on the normal structure of feeding behaviour, or its effects upon orexin‐A‐induced behavioural change. In the present study, we have employed a continuous monitoring technique to characterize the effects of SB‐334867 (3–30 mg/kg, i.p.) on the microstructure of rat behaviour during a 1‐h test with palatable wet mash. Administered alone, SB‐334867 (30 mg/kg, but not lower doses) significantly reduced food intake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Although suggestive of a behaviourally nonselective (i.e. sedative) action, the structure of feeding behaviour was well‐preserved at this dose level, with the reduction in behavioural output clearly attributable to an earlier onset of behavioural satiety. As previously reported, orexin‐A (10 µg per rat i.c.v.) stimulated food intake, increased grooming and delayed the onset of behavioural satiety. Pretreatment with SB‐334867 dose‐dependently blocked these effects of orexin‐A, with significant antagonism evident at dose levels (3–10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions. Together, these findings strongly support the view that orexin‐A is involved in the regulation of feeding patterns and that this influence is mediated through the orexin‐1 receptor.
Laminar specific alterations of thalamocortical projections in organotypic cultures following layer 4 disruption in ferret somatosensory cortex
Authors: Palmer Sidney L. , Noctor Stephen C. , Jablonska Beata , Juliano Sharon L. 
Published: March 2003

AbstractThe developing neocortex influences the growth of thalamocortical projections. Layer 4 in particular receives the majority of input from the thalamus and is important in instructing thalamic afferents to terminate. Previous in vivo experiments demonstrated that disruption of layer 4 during corticogenesis in ferret somatosensory cortex by application of methylazoxy methanol acetate (MAM) prevents proper termination of thalamic afferents in appropriate cortical regions. To further explore the role of layer 4 in thalamocortical development, we prepared organotypic cocultures consisting of normal gestational day 0 (P0) ferret thalamus paired with normal, embryonic day 33 (E33), or E38 MAM‐treated cortex obtained from ferrets at either P0 or P7. Injection of MAM on E33 disrupts layer 4 formation, whereas similar injections on E38 interfere with layer 2 formation. The cocultures grew together for a number of days, then discrete injections of either fluorescent dextrans or 1,1’‐dioctadecyl‐3,3,3′,3′‐tetramethyl‐indocarbocyanine perchlorate (DiI) were made into the thalamic piece. The labeled thalamic afferents that grew into the cortical slice were analysed and the sites of their terminations quantified after 3, 5, or 7–10 days in culture (DIC). Our results varied somewhat with the amount of time in culture, but the preponderance of thalamic fibers in normal cortex terminated in layer 4, whereas their counterparts in E33 MAM‐treated cortex grew beyond the cortical plate and many fibers terminated inappropriately within lower cortical layers or white matter. Terminal distribution of thalamic fibers in E38 MAM‐treated cortex looked similar to normal. These results demonstrate that the cells of layer 4 provide thalamic afferents with important positional and termination cues.
Immunohistochemical characterisation of Fos‐positive cells in brainstem monoaminergic nuclei following intracranial self‐stimulation of the medial forebrain bundle in the rat
Authors: Ishida Yasushi , Nakamura Masato , Ebihara Kosuke , Hoshino Kaeko , Hashiguchi Hiroyuki , Mitsuyama Yoshio , Nishimori Toshikazu , Nakahara Daiichiro 
Published: March 2003

AbstractFos immunostaining was used as a marker of neuronal activity following intracranial self‐stimulation (ICSS) of the medial forebrain bundle (MFB) in the rat, and was combined with immunostaining for tyrosine hydroxylase (TH), serotonin (5‐HT), γ‐aminobutyric acid (GABA), or NR1 (one of the glutamate N‐methyl‐d‐aspartate receptor subunits) for purposes of neurochemical identification. ICSS induced a significant but different degree of increase in the number of Fos‐immunopositive (Fos+) cells in the six brainstem monoaminergic nuclei examined, which included the ventral tegmental area (VTA), substantia nigra pars compacta (SNc), dorsal raphe nucleus (DR), median raphe nucleus (MR), locus coeruleus (LC), and A7 noradrenaline cells. Densely labelled Fos+ cells were observed in the LC following ICSS, and many of these Fos+ cells were colocalized with TH. Similarly, many of Fos+ cells in the A7 and DR/MR were colocalized with TH and 5‐HT, respectively. By contrast, a smaller number of Fos+ cells was detected in the VTA and SNc following the ICSS, and in these regions the majority of Fos+ cells were not colocalized with TH. Although results among regions quantitatively differed, the ICSS induced a significant increase in the number of double‐labelled cells (GABA+/Fos+ or NR1+/Fos+) in all of the VTA, DR, and LC, in which the ICSS produced an ipsilaterally weighted increase in Fos‐like immunoreactivity. These results suggest that ICSS of the MFB induces differential Fos expression within monoaminergic and GABAergic neurons in brainstem monoaminergic nuclei under modulation by glutamatergic afferents.
Effects of STN lesions on simple vs choice reaction time tasks in the rat: preserved motor readiness, but impaired response selection
Authors: Baunez Christelle , Humby Trevor , Eagle Dawn M. , Ryan Lawrence J. , Dunnett Stephen B. , Robbins Trevor W. 
Published: March 2003

AbstractThe subthalamic nucleus (STN) is a key structure within the basal ganglia, inactivation of which is a current strategy for treating parkinsonism. We have previously shown that bilateral lesions of the STN or pharmacological inactivation of this structure in the rat induce multiple deficits in serial reaction time tasks. The aim of the present study was to investigate further a possible role for the STN in response preparatory processes by using simple (SRT) and choice (CRT) reaction time tasks. In contrast to the CRT procedure, the information related to the location of where the response had to be made was given in advance in the SRT procedure. Accurate performance on these tasks requires not only the selection of the correct response (i.e. which response), but also preparation in order to perform when required. A comparison between the two tasks allows assessment of whether STN lesions affect which response (‘which’) or when to perform it (‘when’). As previously observed in these procedures, the responses were faster as a function of the variable foreperiod preceding the trigger stimulus. This well‐known effect, termed ‘motor readiness’, was maintained after STN lesions, suggesting that STN lesions did not affect the ‘when’ phase of action preparation. However, while performance on the SRT was faster than on the CRT task preoperatively, STN lesions slowed RTs and abolished the beneficial effect of advance information, suggesting a deficit in the selection (‘which’) phase of response preparation. This deficit in the selection phase was further supported by deficits in accuracy of responding after STN lesions, as well as increases in mislocated premature responding in the SRT condition. Together, these results suggest that the STN plays an important role in response preparatory processes, including response selection and inhibitory control processes.
Hippocampus and homing in pigeons: left and right hemispheric differences in navigational map learning
Authors: Gagliardo Anna , Ioalè Paolo , Odetti Francesca , Bingman Verner P. , Siegel Jennifer J. , Vallortigara Giorgio 
Published: March 2003

AbstractOne‐month‐old, inexperienced homing pigeons, prior to any opportunity to learn a navigational map, were subjected to either right or left unilateral ablation of the hippocampal formation (HF). These pigeons were then held together with a group of age‐matched control birds in an outdoor aviary, where they were kept for about 3 months with the opportunity to learn a navigational map. When subsequently tested for navigational map learning at about 4 months of age posthatching, control and right HF‐ablated pigeons were equally good at orienting homeward from distant, unfamiliar locations, indicating successful navigational map learning. By contrast, left HF‐ablated pigeons were impaired in orienting homeward, indicating a failure to learn a navigational map. Interestingly, both right and left HF‐ablated pigeons displayed impaired homing performance relative to controls. These results suggest that different aspects of homing pigeon navigation may be lateralized to different hemispheres, and in particular, the HF of the different hemispheres. The left HF appears critical for navigational map learning, i.e. determining an approximate direction home from distant, unfamiliar locations. The right HF, and possibly the left HF as well, appear to play an important role in local navigation near the loft, which is likely based on familiar landmarks.