bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of neuronal density and subfield sizes in the hippocampus of CD95L‐deficient (gld), CD95‐deficient (lpr) and nondeficient mice
Authors: Kovac Adam D. , Grammig Jo , Mahlo Jacqueline , Steiner Barbara , Roth Karl , Nitsch Robert , Bechmann Ingo 
Published: March 2003

AbstractDuring brain development, the majority of neurons undergo programmed cell death. It is now clear that caspases are involved in this process of selective induction of neuronal apoptosis, yet the signals for this caspase activation remain undefined. As an upstream activator of these enzymes, the death receptor CD95 (Fas, APO1) was recently shown on neurons in the cornu ammonis (CA)2 and CA3 hippocampal subfields of early postnatal mice and rats. In vitro, cortical neuroblast cells are susceptible to CD95 ligand (CD95L, FasL, APO‐1 L)‐induced apoptosis. It was therefore suggested that the CD95/CD95L system is involved in neuronal apoptosis during hippocampal development. We therefore performed a blinded study comparing field size and neuronal density in the hippocampi of p20 CD95‐deficient (lpr), CD95L‐deficient (gld) and C57 mice. Whereas field sizes did not differ significantly between these strains, paired Mann–Whitney analyses revealed an increased number of neurons in the CA2 regions of CD95‐deficient mice (P = 0.008), and minor, yet at 1% nonsignificant, differences between gld, lpr and C57 strains in the CA1 and CA3 regions. However, joint comparison of the three strains using the Kruskal–Wallis test rendered all differences insignificant. We conclude that the CD95/CD95L system is either not involved, or can be replaced by alternate mechanisms in the control of neuronal populations during hippocampal development.
Nicotine withdrawal syndrome: behavioural distress and selective up‐regulation of the cyclic AMP pathway in the amygdala
Authors: Tzavara Eleni T. , Monory Krisztina , Hanoune Jacques , Nomikos George G. 
Published: March 2003

AbstractNicotine addiction is a major public health issue. The use of laboratory animal models is a crucial tool in research aiming at understanding the pathophysiological mechanisms of nicotine dependence and at proposing new therapies. In rodents, cessation of nicotine exposure or administration of the nicotinic antagonist mecamylamine induces a nicotine withdrawal syndrome. Antagonist‐precipitated withdrawal from other abused drugs such as opiates or cannabinoids has been associated with region‐specific modifications of the activity of the cyclic AMP pathway. Here we show that mecamylamine‐precipitated nicotine withdrawal in the rat is characterized by an increase in thigmotaxis (time spent in the periphery of an open field) that may be indicative of behavioural distress and can be associated with a selective up‐regulation of adenylyl cyclase activity in the amygdala, a region implicated in the regulation of negative affect in response to aversive stimuli, including withdrawal. Adenylyl cyclase activity that is increased during precipitated nicotine withdrawal is stimulated by calcium/calmodulin, as is also the case for opioid and cannabinoid abstinence. This suggests that directly or indirectly mediated increases in the activity of the cyclic AMP pathway could constitute a possible common molecular mechanism underlying neuroadaptive changes following abstinence from different abused drugs.
Spatial learning is unimpaired in mice containing a deletion of the alpha‐synuclein locus
Authors: Chen Philip E. , Specht Christian G. , Morris Richard G. M. , Schoepfer Ralf 
Published: March 2003

Abstractα‐Synuclein belongs to a family of structurally related proteins expressed highly in the brain and is the major component of filamentous deposits present in a range of neurodegenerative diseases (synucleinopathies). It has been implicated in learning and memory, yet the physiological role of this protein is still unclear. It was recently found that a subpopulation of C57BL/6J mice carries a chromosomal deletion of the α‐synuclein locus, often unknown to the experimenter. As genetically engineered mice are often backcrossed with C57BL/6J animals for learning and memory experiments, we studied the importance of α‐synuclein in spatial learning tasks by examining the performance of α‐synuclein–/– mice in the hidden platform reference memory version of the watermaze. Our data show that α‐synuclein–/– mice had no significant impairment in performance during training or probe trials, compared with wild‐type littermates. Therefore, we conclude that α‐synuclein is not essential for this type of spatial learning.
Auditory activation of ‘visual’ cortical areas in the blind mole rat (Spalax ehrenbergi)
Authors: Bronchti Gilles , Heil Peter , Sadka Ronen , Hess Andreas , Scheich Henning , Wollberg Zvi 
Published: March 2003

AbstractThe mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross‐modal compensation at the cortical level. Cyto‐ and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2‐deoxyglucose and electrophysiological recording of evoked field potentials and single‐unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.
Upregulation of neurokinin‐1 receptor expression in rat spinal cord by an N‐terminal metabolite of substance P
Authors: Velázquez Rubén A. , McCarson Kenneth E. , Cai Yongjiu , Kovács Katalin J. , Shi Qiuying , Evensjö Maria , Larson Alice A. 
Published: March 2003

AbstractChronic inflammatory conditions are associated with an upregulation of both substance P (SP) and neurokinin‐1 (NK‐1) receptors in the dorsal spinal cord. These receptors have been implicated in hyperalgesia as well as stress‐induced analgesia. On the basis of the release of SP during chronic pain, and its rapid metabolism, we tested the hypothesis that SP metabolites regulate the synthesis of either SP or NK‐1 receptors in the spinal cord. We measured expression of preprotachykinin mRNA and NK‐1 receptor mRNA following intrathecally administered substance P(1–7) (SP1–7), the major metabolite of SP in rat, and following capsaicin, a compound known to induce release of endogenous SP. SP(1–7) and capsaicin each increased NK‐1 receptor mRNA in the spinal cord (6 h) followed by an increase in NK‐1 receptor‐immunoreactivity (24 h and 1 week). D‐SP(1–7), a d‐isomer and antagonist of SP(1–7), did not mimic the effect of SP(1–7), indicating stereoselectivity. Instead, D‐SP(1–7) prevented the upregulation of NK‐1 receptor immunoreactivity that was induced by capsaicin injected intrathecally, suggesting that the effect of capsaicin is also mediated by SP N‐terminal metabolites. In contrast, the decrease in SP synthesis produced by capsaicin was not dependent on SP metabolites as SP(1–7) failed to decrease either preprotachykinin mRNA content in dorsal root ganglia (6 h) or SP immunoreactivity in the lumbar spinal cord (24 h and 1 week). In addition, the effects of capsaicin on SP synthesis were not prevented by D‐SP(1–7). Thus, SP metabolites, at times and doses that are antinociceptive, appear to enhance SP‐mediated signal transduction by upregulating NK‐1 receptor expression without affecting SP synthesis.
Peripheral GABAergic inhibition of spider mechanosensory afferents
Authors: Panek Izabela , French Andrew S. , Seyfarth Ernst‐August , Sekizawa Shin‐ichi , Torkkeli Päivi H. 
Published: March 2003

AbstractSpider mechanosensory neurons receive an extensive network of efferent synapses onto their sensory dendrites, somata and distal axonal regions. The function of these synapses is unknown. Peripheral synapses are also found on crustacean stretch‐receptor neurons but not on mechanosensory afferents of other species, although inhibitory GABAergic synapses are a common feature of centrally located axon terminals. Here we investigated the effects of GABA receptor agonists and antagonists on one group of spider mechanosensory neurons, the slit sense organ VS‐3, which are accessible to current‐ and voltage‐clamp recordings. Bath application of GABA activated an inward current that depolarized the membrane and increased the membrane conductance leading to impulse inhibition. VS‐3 neuron GABA receptors were activated by muscimol and inhibited by picrotoxin but not bicuculline, and their dose–response relationship had an EC50 of 103.4 µm, features typical for insect ionotropic GABA receptors. Voltage‐ and current‐clamp analysis confirmed that, while the Na+ channel inhibition resulting from depolarization can lead to impulse inhibition, the increase in membrane conductance (i.e. ‘shunting’) completely inhibited impulse propagation. This result argues against previous findings from other preparations that GABA‐mediated inhibition is caused by a depolarization that inactivates Na+ conductance, and it supports those findings that assign this role to membrane shunting. Our results show that GABA can rapidly and selectively inhibit specific mechanoreceptors in the periphery. This type of peripheral inhibition may provide spiders with a mechanism for distinguishing between signals from potential prey, predators or mates, and responding with appropriate behaviour to each signal.
Brain temperature fluctuation: a reflection of functional neural activation
Authors: Kiyatkin Eugene A. , Brown P. Leon , Wise Roy A. 
Published: March 2003

AbstractAlthough it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature.
Neurotensin phase‐shifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro
Authors: Meyer‐Spasche Alert , Reed Helen E. , Piggins Hugh D. 
Published: March 2003

AbstractThe suprachiasmatic nuclei (SCN) of the hypothalamus house the main mammalian circadian pacemaker. Cell bodies in the rat SCN contain the neuropeptide neurotensin (NT), and two NT receptor types, NTS1 and nts2. Because the role of NT in the circadian rhythm processes is unknown, we studied the phase‐shifting effects of NT on the firing rate rhythm of rat SCN neurons in vitro. Additionally, the NT receptor antagonists SR142948a and SR48692 were used to try and block any NT‐induced phase shifts. To elucidate the second messenger pathway responsible for mediating the phase‐resetting actions of NT, we utilized the phospholipase C (PLC) and protein kinase A (PKA) inhibitors U‐73122 and KT5720, respectively. Application of NT during the projected day resulted in a large advance in the time of peak in FRR, whereas treatments during the projected night had no effect. Both NT receptor antagonists blocked the NT‐induced phase shifts, as did the PLC inhibitor U‐73122. The PKA inhibitor KT5720 had no influence on the magnitude of the phase shift caused by NT during the middle of the projected day. These results provide the first evidence that NT may play a role in regulating the rat circadian pacemaker, using NTS1 and nts2 receptors presumably coupled to PLC.
AMPA receptor activation induces GABA release from neurons migrating tangentially in the intermediate zone of embryonic rat neocortex
Authors: Poluch Sylvie , König Norbert 
Published: March 2003

AbstractIn the intermediate zone of the embryonic rodent neocortex, neurons migrating tangentially from the basal ganglia express both functional amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors and γ‐aminobutyric acid (GABA). To test the hypothesis of GABA release triggered by AMPA receptor activation, we used whole‐hemisphere cultures prepared from rat embryos (day 15). We observed a marked decrease in the number of detectable GABA‐positive cells in the intermediate zone after exposure to T‐AMPA. This effect was blocked by coapplying GYKI 53655, an AMPA receptor antagonist. The decrease in GABA immunolabelling induced by T‐AMPA did not require extracellular calcium. In contrast, it was abolished after sodium substitution by choline, or after coapplication of nipecotic acid, a GABA transporter inhibitor. Exposure to high potassium reduced the number of detectable GABA‐positive cells. These results are compatible with carrier‐mediated GABA release consecutive to sodium influx. GABA released from neurons migrating tangentially in the intermediate zone after AMPA receptor activation may influence neighbouring elements including radially migrating postmitotic neurons, proliferating progenitors and possibly the tangential cells themselves.
Layer‐specific thalamocortical innervation in organotypic cultures is prevented by substances that alter neural activity
Authors: Anderson Gillian , Price David J. 
Published: March 2003

SummaryCortical layer IV is the major target of thalamocortical axons and many previous studies have shown that the development of this layer‐specific innervation can be modelledin vitroby organotypic cocultures of thalamus and cortex. The mechanisms causing thalamic axons to terminate in layer IV are unknown. We used thesein vitromodels to test the possibility that neural activity plays a part in this termination process by adding substances that raise or lower levels of neural activity to the cocultures. We found that addition of tetrodotoxin or 2‐amino‐5‐phosphonovalerate, to block activity, or potassium, to raise it, all interfered with termination in layer IV. These findings suggest that termination in layer IV requires neural activity at an appropriate level in the thalamocortical system. They also add support to recent findings that show that the importance of neural activity in development may extend to an earlier period than thought previously, to include the correct targeting of axons as well as the later refinement of connections.
Cloning and functional characterization of two glycine receptor α‐subunits from the perch retina
Authors: Gisselmann G. , Galler A. , Friedrich F. , Hatt H. , Bormann J. 
Published: March 2003

AbstractGlycine receptors are ligand‐gated ion channel proteins mediating synaptic inhibition in the spinal cord, retina and brain of vertebrates. We have cloned and functionally characterized two glycine receptor α‐subunits from the perch (Roccus americana) retina. Based on sequence homology with the mammalian counterparts, we termed these subunits α1 and α3. RT‐PCR revealed the presence of both subunits in retina and brain, whereas α1 was predominant in spinal cord. A short splice variant of α1 was detected in the brain but not in the retina. Functional expression of the perch subunits in HEK‐293 cells yielded robust glycine‐gated currents sensitive to strychnine. The perch receptors displayed a high efficacy for taurine and GABA and thus differ from the mammalian counterparts. Because the retina is a rich source for taurine, this finding could be of physiological importance. The structural features of the ligand binding domain strongly support the notion of increased glycine/GABA discrimination in higher vertebrates.
Ciguatoxin‐induced oscillations in membrane potential and action potential firing in rat parasympathetic neurons
Authors: Hogg R. C. , Lewis R. J. , Adams D. J. 
Published: March 2003

AbstractThe actions of ciguatoxins from the Pacific (P‐CTX‐1) and Caribbean (C‐CTX‐1) regions were investigated in isolated parasympathetic neurons from rat intracardiac ganglia using patch‐clamp recording techniques. Under current‐clamp conditions, bath application of P‐CTX‐1 (1–10 nm) or C‐CTX‐1 (10–30 nm) caused a gradual depolarization that was accompanied by oscillation of the membrane potential leading to tonic action potential firing. Membrane potential oscillations were observed between −45 and −60 mV and had an amplitude of 10–20 mV and a mean frequency of 10 Hz. Oscillation frequency was temperature‐dependent with a Q10 of 2.0. Membrane oscillations were temporarily inhibited by hyperpolarizing current pulses and potentiated by weak depolarizing current pulses. The amplitude of oscillations was reduced upon lowering the external Na+ concentration and inhibited by tetrodotoxin (TTX), tetracaine or Zn2+. Tetraethylammonium, 4‐aminopyridine, Cs+, Cd2+, Ba2+, 1,4,4′‐diothiocyanato‐2,2′‐stilbenedisulphonic acid (DIDS) and ouabain had no effect on the CTX‐1‐induced membrane depolarization and oscillations. Brevetoxin (PbTx‐3, 100 nm), in contrast to CTX‐1, caused a membrane depolarization that was not associated with oscillation of the membrane potential. Under voltage‐clamp conditions, P‐CTX‐1 inhibited the peak amplitude of the voltage‐dependent Na+ current and shifted the activation curve to more negative potentials, but membrane oscillations were not seen in this configuration. These results suggest that ciguatoxins cause oscillation of the membrane potential in mammalian autonomic neurons by modifying the activation and inactivation properties of a population of TTX‐sensitive Na+ channels.
Differential modulation of Ih by 5‐HT receptors in mouse CA1 hippocampal neurons
Authors: Bickmeyer Ulf , Heine Martin , Manzke Till , Richter Diethelm W. 
Published: March 2003

AbstractCA1 pyramidal neurons of the hippocampus express various types of serotonin (5‐HT) receptors, such as 5‐HT1A, 5‐HT4 and 5‐HT7 receptors, which couple to Gαi or Gαs proteins and operate on different intracellular signalling pathways. In the present paper we verify such differential serotonergic modulation for the hyperpolarization‐activated current Ih. Activation of 5‐HT1A receptors induced an augmentation of current‐induced hyperpolarization responses, while the responses declined after 5‐HT4 receptors were activated. The resting potential of neurons hyperpolarized (−2.3 ± 0.7 mV) after 5‐HT1A receptor activation, activation of 5‐HT4 receptors depolarized neurons (+3.3 ± 1.4 mV). Direct activation of adenylyl cyclase (AC) by forskolin also produced a depolarization. In voltage clamp, the Ih current was identified by its characteristic voltage‐ and time‐dependency and by blockade with CsCl or ZD7288. Activation of 5‐HT1A receptors reduced Ih and shifted the activation curve to a more negative voltage by −5 mV at half‐maximal activation. Activation of 5‐HT4 and 5‐HT7 receptors increased Ih and shifted the activation curve to the right by +5 mV. Specific activation of 5‐HT4 receptors by BIMU8 increased membrane conductance and showed an increase in Ih in a subset of cells, but did not induce a significant alteration in the activation curve. In order to verify spatial differences, we applied BIMU8 selectively to the soma and to the dendrites. Only somatic application induced receptor activation. These data are confirmed by immunofluorescence stainings with an antibody against the 5‐HT4A receptor, revealing receptor expression at the somata of the CA1 region. A similar expression pattern was found with a new antibody against 5‐HT7 receptors which reveals immunofluorescence staining on the cell bodies of pyramidal neurons.
Early sequential formation of functional GABAA and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus
Authors: Hennou Sonia , Khalilov Ilgam , Diabira Diabé , Ben‐Ari Yehezkel , Gozlan Henri 
Published: March 2003

AbstractDuring postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch‐clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin‐filled neurons. At P0, three types of interneurons were found: (i) non‐innervated ‘silent’ interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABAA synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non‐innervated neurons and interneurons with GABAA and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18–20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA–glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.
Modelling of the III–IV loop, a domain involved in calcium channel Cav2.1 inactivation, highlights a structural homology with the γ subunit of G proteins
Authors: Fathallah Mohamed , Sandoz Guillaume , Mabrouk Kamel , Geib Sandrine , Urbani Julie , Villaz Michel , Ronjat Michel , Sabatier Jean‐Marc , De Waard Michel 
Published: March 2003

AbstractWe have modelled the conformation of the III–IV loop of the Cav2.1 subunit of P/Q calcium channels, a loop that is implicated in fast voltage‐dependent inactivation. Change in channel inactivation requires its direct interaction with the I–II loop. This interaction occurs with an affinity in the order of 70 nm. Intracellular injection of a 40‐mer III–IV loop‐derived peptide produces an increase in the rate of fast inactivation. This alteration in channel kinetic is also accompanied by a hyperpolarizing shift in the steady‐state voltage‐dependence of inactivation. None of these effects are observed in the presence of a β subunit, suggesting the existence of a competitive mechanism of action between the β subunit and the III–IV loop. Amino acid sequence comparison using BLAST reveals that the III–IV loop shares 53% identity with the γ subunit of G proteins. Because of the pivotal contribution of the III–IV loop to inactivation, an atomic model of the III–IV loop was generated by both homology modelling and molecular mechanics calculations. Using the X‐ray structures of the βγ dimer of the heterotrimeric G‐proteins as templates, the III–IV loop is predicted to contain a well‐structured α‐helix at the amino‐terminus with both the N‐ and C‐termini having the same orientation in the plane of the inner lipid bilayer. We provide a hypothetical working model in which we propose that the III–IV loop interacts with the I–II loop via its Gβγ binding domain.