bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noradrenaline Modulates GIutamate‐mediated Neurotransmission in the Rat Basolateral Amygdala In Vitro
Authors: Ferry Barbara , Magistretti Pierre J. , Pralong Etienne 
Published: April 2006

AbstractThe entorhinal cortex and the amygdala are interconnected structures of the limbic system in which paroxysmal activity occurs during temporal lobe epilepsy. Conflicting evidence shows that noradrenaline (i) inhibits the spreading to other parts of the limbic system of paroxysmal activity generated in the amygdala or the entorhinal cortex, but also (ii) increases glutamatergic transmission in the basolateral amygdala. Given our previous work on the inhibitory effect of noradrenaline on entorhinal cortex neurons, we developed an in vitro slice preparation to study the synaptic transmission in the basolateral amygdala and its modulation by noradrenaline. Noradrenaline reduced the fast excitatory postsynaptic potential (EPSP) by ∼40% at 100 μM and the slow EPSP by ∼50% at 50 μM. A similar effect was obtained with the α2‐agonist UK 14304 at 100 and 50 μM respectively. In contrast, the β‐agonist isoproterenol increased the fast EPSP by ∼40% at 100 μM and the slow EPSP by ∼20% at 50 μM. Accordingly, the effect of noradrenaline on the EPSPs was blocked by the α2‐antagonist yohimbine (10 μM) but not by the α1‐antagonist prazosine (10 μM) and the β‐antagonist propranolol (10 μM). Noradrenaline (50–100 μM) was ineffective on most (14/16) of the isolated inhibitory postsynaptic potentials (IPSPs). These experiments provide evidence that noradrenaline inhibits the excitatory synaptic response of basolateral amygdala neurons. A pharmacological analysis revealed that the noradrenergic modulation of the excitatory transmission in the basolateral amygdaia can be dissected into a predominant α2‐adrenoreceptor‐mediated inhibition and a β‐adrenoreceptor‐mediated excitation.
How Reliably Does a Neuron in the Visual Motion Pathway of fhe Fly Encode Behaviourally Relevant Information?
Authors: Warzecha Anne‐Kathrin , Egelhaaf Martin 
Published: April 2006

AbstractHow reliably neurons convey information depends on the extent to which their activity is affected by stochastic processes which are omnipresent in the nervous system. The functional consequences of neuronal noise can only be assessed if the latter is related to the response components that are induced in a normal behavioural situation. In the present study the reliability of neural coding was investigated for an identified neuron in the pathway processing visual motion information of the fly (Lucilia cuprina). The stimuli used to investigate the neuronal performance were not exclusively defined by the experimenter. Instead, they were generated by the fly itself, i.e. by its own actions and reactions in a behavioural closed‐loop experiment, and subsequently replayed to the animal while the activity of an identified motion‐sensitive neuron was recorded. Although the time course of the neuronal responses is time‐locked to the stimulus, individual response traces differ slightly from each other due to stochastic fluctuations in the timing and number of action potentials. Individual responses thus consist of a stimulus‐induced and a stochastic response component. The stimulus‐induced response component can be recovered most reliably from noisy neuronal signals if these are smoothed by intermediate‐sized time windows (40–100 ms). At this time scale the best compromise is achieved between smoothing out the noise and maintaining the temporal resolution of the stimulus‐induced response component. Consequently, in the visual motion pathway of the fly, behaviourally relevant motion stimuli can be resolved best at a time scale where the timing of individual spikes does not matter.
GABA‐ and Glutamate‐evoked Responses in the Rat Ventral Pallidum are Modulated by Dopamine
Authors: Johnson Patricia I. , Napier T. Celeste 
Published: April 2006

AbstractMicroiontophoresis was used to investigate the influence of dopamine on GABA‐ and glutamate‐induced responses from ventral pallidal neurons recorded extracellularly in chloral hydrate‐anaesthetized rats. Modulation was determined by comparing dopamine‐induced alterations in amino acid‐induced activity (‘signal’) with dopamine‐induced effects on spontaneous firing (‘noise’). A dopamine ejection current‐response curve was generated to determine the current levels that did not alter spontaneous firing (‘subthreshold’) and those that produced ∼50% of the maximal dopamine‐induced response (ECur50). Co‐iontophoresis of dopamine with GABA generally diminished the inhibitory influence of GABA on pallidal neuron firing; 70% of neurons tested with ECur50 dopamine demonstrated a decrease in the signal‐to‐noise ratio whereas 10% displayed an increase. At subthreshold dopamine ejection currents, 59% of neurons responded with a decrease and 18% responded with an increase in the GABA signal‐to‐noise ratio. When ECur50 dopamine was co‐iontophoresed with glutamate, 84% of the neurons displayed a decrease in the signal‐to‐noise ratio for glutamate‐evoked excitations whereas 11% demonstrated an increase. Subthreshold dopamine ejection currents decreased the signal‐to‐noise ratio in 62% of the ventral pallidal neurons excited by glutamate and increased the ratio in 23%. These data illustrate that dopamine substantially alters GABA‐ and glutamate‐evoked responses even at ejection currents that are below those necessary to change spontaneous firing. Thus, it appears that neuromodulation is an important means by which dopamine influences ventral pallidal neuronal activity.
Subthalamic Ablation Reverses Changes in Basal Ganglia Oxidative Metabolism and Motor Response to Apomorphine Induced by Nigrostriatal Lesion in Rats
Authors: Blandini Fabio , Garcia‐Osuna Monica , Greenamyre J. Timothy 
Published: April 2006

AbstractIn Parkinson's disease, the functional architecture of the basal ganglia nuclei undergoes profound alterations, one of the most important of which is overactivity of the basal ganglia output nuclei. This phenomenon seems to be intimately related to pathological overactivity of the subthalamic nucleus, which directly modulates the basal ganglia output through its glutamatergic projections. In this study, we investigated the effects of unilateral subthalamic nucleus lesions on the activities of succinate dehydrogenase and cytochrome oxidase, two markers of neuronal activity, in rats with prior unilateral lesions of the nigrostriatal tract. We also explored the effect of subthalamic nucleus lesions on the rotational response to systemic apomorphine. Rats with unilateral lesions of the nigrostriatal tract showed ipsilateral increases in enzyme activity in the basal ganglia output nuclei, entopeduncular nucleus and substantia nigra pars reticulata. Selective subthalamic nucleus destruction completely reversed this phenomenon. In addition, subthalamic nucleus lesions abolished the rotational response to apomorphine. These results confirm that overactivity of the subthalamic nucleus plays a pivotal role in the functional alterations of basal ganglia associated with Parkinson's disease. They also shed further light on the neural mechanisms through which manipulations of subthalamic activity can ameliorate Parkinson's disease symptoms
Diffusion in Axon Guidance
Authors: Goodhill Geoffrey J. 
Published: April 2006

AbstractAxon guidance by target‐derived diffusible factors plays an important role in the development of the nervous system. This paper considers the constraints imposed on this process by the mathematics of diffusion. A point source continuously producing a factor into an infinite three‐dimensional volume is considered as a model for both the in vivo and in vitro situation. Basic constraints for effective guidance are assumed to be that the concentration falls between certain maximum and minimum limits, and that the percentage change in concentration across the width of the growth cone exceeds a certain minimum value. The evolution of the shape of the gradient over time is analysed. Using biologically reasonable parameter values, it is shown that the maximum range over which growth cone guidance by a diffusible factor is possible for large times (several days) after the start of the production of the factor is 500–1000 μm. This maximum distance is independent of the diffusion constant of the diffusing molecule, applies to both chemoattractants and chemorepellents, and agrees with experimental data. At earlier times, however, the constraints may be satisfied for distances up to several millimetres. The time it takes for this maximum guidance distance to fall to the asymptotic value depends on the diffusion constant. This time is a few hours for a small molecule but as much as a few days for a large molecule. The model therefore predicts that guidance over distances larger than 1000 μm is possible if the start of production of the factor is carefully matched to the time when guidance is required.
Expression of Pro‐Inflammatory Cytokine and Chemokine mRNA Upon Experimental Spinal Cord Injury in Mouse: an In Situ Hybridization Study
Authors: Bartholdi Deborah , Schwab Martin E. 
Published: April 2006

AbstractInjury to the spinal cord induces a complex cascade of cellular reactions at the local lesion area: secondary cell death and inflammatory reactions as well as scar and cavity formation take place. In order to investigate the molecular features underlying this local wounding response and to determine their pathophysiological implications, we studied the expression pattern of pro‐inflammatory and chemoattractant cytokines in an experimental spinal cord injury model in mouse. We show by in situ hybridization that transcripts for the pro‐inflammatory cytokines TNFα and IL‐1 as well as the chemokines MIP‐1 α and MIP‐1β are upregulated within the first hour following injury. In this early phase, the expression of the pro‐inflammatory cytokines is restricted to cells in the surroundings of the lesion area probably resident CNS cells. While TNFα is expressed in a very narrow time window, IL‐1 can be detected in a second phase in a subset of polymorphonuclear granulocytes which immigrate into the spinal cord around 6 h. Message for the chemokines MIP‐1α and β is expressed in a generalized way in the grey matter of the entire spinal cord around 24 h and gets again restricted to the cellular infiltrate at the lesion site at 4 days following injury. Interestingly, our data suggest that resident CNS cells, most probably microglial cells, and not peripheral inflammatory cells, are the main source for cytokine and chemokine mRNAs. The defined cytokine pattern observed indicates that the inflammatory events upon lesioning the CNS are tightly controlled. The very early expression of pro‐inflammatory cytokine and chemokine messages may represent an important element of the recruitment of inflammatory cells. Additional pathophysiological consequences of the specific cytokine pattern observed remain to be determined.
NMDA Receptor Properties in Rat Supraoptic Magnocellular Neurons: Characterization and Postnatal Development
Authors: Hussy Nicolas , Boissin‐Agasse Line , Richard Philippe , Desarménien Michel G. 
Published: April 2006

AbstractHypothalamo‐neurohypophysial magnocellular neurons display specific electrical activities in relation to the mode of release of their hormonal content (vasopressin or oxytocin). These activities are under strong glutamatergic excitatory control. The implication of NMDA receptors in the control of vasopressinergic and oxytocinergic neurons is still a matter of debate. We here report the first detailed characterization of functional properties of NMDA receptors in voltage‐clamped magnocellular neurons acutely dissociated from the supraoptic nucleus. All cells responded to NMDA with currents that reversed polarity around 0 mV and were inhibited by D‐2‐amino‐5‐phosphonovalerate (d‐APV) and by 100 μM extracellular Mg2+ (at ‐80 mV). Sensitivity to the co‐agonist glycine (EC50, 2 μM) was low compared with most other neuronal preparations. The receptors displayed low sensitivity to ifenprodil, were insensitive to glycine‐independent potentiation by spermine, and had a unitary conductance of 50 pS. No evidence was found for two distinct cell populations, suggesting that oxytocinergic and vasopressinergic neurons express similar NMDA receptors. Characterization of NMDA receptors at different postnatal ages revealed a transient increase in density of NMDA currents during the second postnatal week. This was accompanied by a specific decrease in sensitivity to d‐APV, with no change in NMDA sensitivity or any other properties studied. Supraoptic NMDA receptors thus present characteristics that strikingly resemble those of reconstituted receptors composed of NR1 and NR2A subunits. Understanding the functional significance of the development of NMDA receptors in the supraoptic nucleus will require further knowledge about the maturation of neuronal excitability, synaptic connections and neurohormone release mechanisms.
Influence of Interleukin‐6 on Neural Activity and Transcription of the Gene Encoding Corticotrophin‐releasing Factor in the Rat Brain: An Effect Depending Upon the Route of Administration
Authors: Vallières Luc , Lacroix Steve , Rivest Serge 
Published: April 2006

AbstractInterleukin‐6 (IL‐6) is a pleiotropic cytokine produced by various lymphoid and neural cells. In addition to its classic role during immune and inflammatory responses, IL‐6 acts on the central nervous system to elicit changes, such as activation of the hypothalamic‐pituitary‐adrenal (HPA) axis. This study investigated the effects of systemic and central injection of IL‐6 on neural activity and transcription of the corticotrophin‐releasing factor (CRF) gene in the brain of conscious rats. The animals were killed 1 and 3 h after a single infusion of IL‐6 into the right jugular vein (0.83 or 3.0 μg) or the right lateral ventricle (0.2 μg) and their brains cut from the olfactory bulb to the end of the medulla in 30‐μm coronal sections. Messenger RNA encoding the protein Fos, a marker of neural activity, and the neuropeptide CRF were localized by in situ hybridization histochemistry using 35S‐labelled exonic and intronic riboprobes. The results show that systemic injection of IL‐6 induced specific transcription of c‐fos gene in most of the sensorial circumventricular organs, including the organum vasculosum lamina terminalis, subfornical organ, median eminence, and area postrema, as well as in the central nucleus of the amygdala and bed nucleus of the stria terminalis. On the other hand, central injection of IL‐6 increased cellular level of c‐fos mRNA in the ependymal layer and the walls of the ventricles, meninges, nucleus of the solitary tract, and circumventricular organs. These effects were rapid and transient, since the signals for c‐fos mRNA were detected 1 h after both treatments and vanished 3 h afterwards. Moreover, the CRF gene was not activated by either systemic or central administration of IL‐6 in the paraventricular nucleus of the hypothalamus. Taken together, these results suggest that circumventricular organs hold a privileged position in mediating the central effects of systemic IL‐6 and that centrally injected IL‐6 can strongly activate cells of the ventricular system and surrounding structures. Although this differential circuitry may explain distinct origin‐dependent functions of IL‐6, this cytokine seems insufficient, in itself, to induce transcription of the gene encoding neuroendocrine CRF, the neuropeptide responsible for control of the HPA axis.
Voltage Oscillations in Xenopus Spinal Cord Neurons: Developmental Onset and Dependence on Co‐activation of NMDA and 5HT Receptors
Authors: Scrymgeour‐Wedderburn John F. , Reith Carolyn A. , Sillar Keith T. 
Published: April 2006

AbstractThe development of intrinsic, N‐methyl‐D‐aspartate (NMDA) receptor‐mediated voltage oscillations and their dependence on co‐activation of 5‐hydroxytryptamine (5HT) receptors was explored in motor neurons of late embryonic and early larval Xenopus laevis. Under tetrodotoxin, 100 μM NMDA elicited a membrane depolarization of around 20 mV, but did not lead to voltage oscillations. However, following the addition of 2–5 μM 5HT, oscillations were observed in 12% of embryonic and 70% of larval motor neurons. The voltage oscillations depended upon co‐activation of NMDA and 5HT receptors since they were curtailed by selectively blocking NMDA receptors with D‐2‐amino‐5‐phosphonovaleric acid (APV) or by excluding Mg2+ from the experimental saline. 5HT applied in the absence of NMDA also failed to elicit oscillations. Oscillations could be induced by the non‐selective 5HT1a receptor agonist, 5‐carboxamidotryptamine (5CT) and both 5HT‐ and 5CT‐induced oscillations were abolished by pindobind‐5HT1, a selective 5HT1a receptor antagonist. To test whether 5HT enables voltage oscillations by modulating the voltage‐dependent block of NMDA channels by Mg2+, membrane conductance was monitored under tetrodotoxin. Although 5HT caused membrane hyperpolarization of 4–8 mV, there was little detectable change in conductance. NMDA application caused an approximate 20 mV depolarization and an ‘apparent’ decrease in conductance, presumably due to the conductance pulse bringing the membrane into a voltage region where Mg2+ blocks the NMDA ionophore. 5HT further decreased conductance, which we propose is due to its enhancement of the voltage‐dependent Mg2+ block. When the membrane potential was depolarized by ∼20 mV via depolarizing current injection (to mimic the NMDA‐induced depolarization), 5HT increased rather than decreased membrane conductance. Furthermore, 5HT did not affect the increase in membrane conductance following NMDA applications in zero Mg2+ saline. The results suggest that intrinsic, NMDA receptor‐mediated voltage oscillations develop in a brief period after hatching, and that they depend upon the co‐activation of 5HT and NMDA receptors. The enabling function of 5HT may involve the facilitation of the voltage‐dependent block of the NMDA ionophore by Mg2+ through activation of receptors with 5HT1a‐like pharmacology.
Evidence for Neurotensin Autoreceptors and Relationship of Neurotensin and its Receptors with Tyrosine Hydroxylase‐positive Neurons in Rat Primary Hypothalamic CuItures
Authors: Bachelet Claude‐Marie , Scarcériaux Valerie , Rostène William , Pélaprat Didier 
Published: April 2006

AbstractNeurotensin is present in high quantity in the hypothalamus, where it regulates pituitary hormone secretion. A relationship between dopaminergic and neurotensinergic systems has been suggested in the hypothalamus in studies showing an effect of neurotensin on tuberoinfundibular dopaminergic neurons. In order to determine the anatomical basis of such interactions, primary cultures of rat hypothalamic neurons were used. Tyrosine hydroxylase and neurotensin containing cells were identified by immunocytochemistry and neurotensin binding sites by [125I]Tyr3‐neurotensin autoradiography. Colocalization studies showed that neurotensin immunoreactivity was present in 16% of tyrosine hydroxylase‐positive cells, and that these neurotensinhyrosine hydroxylase neurons represented more than half (58%) of the neurotensinergic population. Five percent of the tyrosine hydroxylase‐positive cells had neurotensin binding sites, suggesting that only a restricted number of hypothalamic dopaminergic neurons is responsive to neurotensin. Neurotensin binding sites were also found on some neurotensin‐positive cells, demonstrating for the first time the presence of autoreceptors for this peptide on neurons. These results in primary cultures provide a cellular basis for direct effects of neurotensin on a subpopulation of hypothalamic dopaminergic cells, and support the possibility of an autocrine action of neurotensin in the hypothalamus.
Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity
Authors: Leist Marcel , Fava Eugenio , Montecucco Cesare , Nicotera Pierluigi 
Published: April 2006

AbstractEndogenous generation of nitric oxide and its congeners, including peroxynitrite (ONOO‐), has been implicated in the mechanism of neuron loss in neurodegenerative diseases. Accordingly, nitric oxide donors and ONOO‐can elicit both apoptosis and necrosis in neuron cultures. Here we show that nitric oxide donors and ONOO‐ are each able to trigger apoptosis of mouse cerebellar granule cells by an excitotoxic mechanism requiring exocytosis and NMDA receptor‐mediated intracellular Ca2+ overload. This conclusion is supported by the following findings. Apoptosis was induced by various nitric oxide donors or by direct addition of ONOO‐ to differentiated cerebellar granule cell cultures that were sensitive to NMDA toxicity, but not in cerebellar granule cells that did not display NMDA‐induced cell death (i.e. early days in culture) or in various glial cell populations. Donors of ONOO‐ or nitric oxide stimulated a sustained increase in intracellular Ca2+, which was prevented by inhibitors of NMDA receptors, such as MK‐801 and 5‐phospho‐aminovaleric acid, or by dampening neuronal electrical activity with high concentrations of extracellular Mg2+. Moreover, these treatments and the exposure of cerebellar granule cells in nominally Ca2+‐free media prevented apoptotic cell death. Both the intracellular Ca2+ increase and apoptosis elicited by ONOO‐ or the nitric oxide donors were prevented by blocking exocytosis with tetanus toxin or botulinum neurotoxin C.
Neurons in the Rat Occipital Cortex Co‐expressing the Substance P‐Receptor and GABA: a Comparison Between In Vivo and Organotypic Cultures
Authors: Echevarría D. , Matute C. , Albus K. 
Published: April 2006

AbstractThe morphology and the distribution of neurons expressing the NK1‐receptor (NK1R) and the co‐expression of γ‐aminobutyric acid (GABA) in these neurons were studied in the rat occipital cortex and in organotypic cultures (OTCs) derived from this structure. By employing immunohistochemistry, we demonstrate that the NK1R‐expressing neurons are non‐pyramidal neurons and co‐express GABA. Some differences were noted between in vivo and OTCs. NK1 R‐expressing neurons in OTCs had larger somata and longer dendrites and the proportion stained with an anti‐GABA‐antibody (∼50%) was smaller than in vivo (90%). The preferential location of NK1 R‐expressing neurons in layers II/III and VI, seen in vivo is not present in OTCs where these neurons distribute rather homogeneously through layers Il‐VI. Our findings imply that in contrast to the cat and monkey, in the rat occipital cortex the effects of substance P are almost exclusively mediated via inhibitory interneurons.