Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons.

International audienceThe effect of 5-HT on activity of noradrenergic locus coeruleus (LC) neurons was studied using microiontophoretic and micropressure drug application in anesthetized rats. 5-HT had no consistent effect on LC spontaneous discharge, eliciting a modest decrease overall. However, 5-HT reliably attenuated responses of LC neurons to excitatory amino acids (EAAs), one of the major classes of transmitters in afferents to these neurons. This effect was specific for EAA responses because it occurred for glutamate and kainate but not for ACh. In contrast, iontophoretic norepinephrine (NE) selectively attenuated spontaneous activity but not responses evoked by either glutamate or ACh. The responsiveness of LC neurons to EAAs as quantified by a response-contrast measure (evoked excitation/basal activity) was markedly reduced by 5-HT, but was increased by NE. For ACh, such responsiveness of LC cells was not changed by 5-HT, but was increased by NE. The effects of 5-HT were prevented and reversed by iontophoretically applied antagonists of 5-HT receptors, methysergide and methiothepin. Thus, 5-HT appears to selectively interact with EAA responses of LC neurons, acting as a filter to attenuate LC activity linked to its major EAA inputs while allowing other channels afferent to the LC (e.g., those utilizing ACh) to be expressed

Inhibition of nigral dopamine neurons by systemic and local apomorphine: Possible contribution of dendritic autoreceptors

International audiencePeripheral administration of low doses of dopamine agonist apomorphine induces a strong and short-latency inhibition of dopamine neurons in the substantia nigra, presumably via the activation of somatodendritic autoreceptors. We studied the site of action of apomorphine in anesthetized rats using volume-controlled pressure microejection combined with single unit recordings. Microapplication of apomorphine in the immediate vicinity of nigral dopamine neurons did not mimic the effect of intravenous administration of apomorphine (50 micrograms/kg), regardless of the concentration or volume used (10(-10)-10(-2) M, 10-100 nl). In contrast, the inhibition produced by systemic apomorphine was mimicked by drug application at a site 300 microns lateral and 600 microns ventral from the recording site in the zona reticulata of the substantia nigra, a region rich in dendrites of dopamine neurons. The inhibition induced by such a distant application of apomorphine could be reversed by systemic injection of D2, but not D1, receptor antagonists. Non-dopaminergic substances such as GABA, bicuculline or lidocaine were more effective when ejected close to rather than distant from the recording site, in a manner opposite to that of apomorphine. Similar to apomorphine, dopamine and D2 receptor agonists were more potent when intranigral applications were made at sites distant from, rather than close to, the recorded dopamine cells. Ejection of D2 antagonists in the substantia nigra zona reticulata attenuated the inhibitory effect of subsequent systemic apomorphine. Our results, together with other previous studies on the location of D2 receptors on dopamine neurons, suggest that peripheral administration of low doses of apomorphine inhibits nigral dopamine neurons by acting at D2 receptors located on the dendrites of these neurons

Serotonin Differentially Modulates Responses Mediated by Specific Excitatory Amino Acid Receptors in the Rat Locus Coeruleus

International audienceMicroiontophoretic application of selective agonists for the three major excitatory amino acid receptors, N-methyl-D-aspartate (NMDA), quisqualate and kainate, increased the discharge rate of noradrenergic locus coeruleus (LC) neurons in vivo. NMDA activation was selectively attenuated by iontophoretic application of 2-amino-5-phosphonopentanoate (AP5), an antagonist at NMDA receptors, whereas kainate- and quisqualate-evoked responses were attenuated by both NMDA and non-NMDA antagonists iontophoresis. NMDA- and quisqualate-evoked responses were significantly decreased by co-iontophoresis of serotonin (5-HT). When the NMDA receptor-mediated component of the response to kainate was blocked with AP5 iontophoresis, 5-HT increased the response of LC neurons to kainate. These results revealed that 5-HT differentially modulates the responsiveness of LC neurons to excitatory amino acids, depending on the receptor subtypes responsible for the neuronal activation

[Participation of NMDA receptors in spontaneous burst firing of dopaminergic mesencephalic neurons].

International audienceIn the rat, somatodendritic application of the NMDA antagonist AP-5, within the Substantia Nigra Zona Compacta and Ventral Tegmental Area, either by micro-iontophoresis or pressure ejection, reduces burst firing of dopamine neurons. Similar local application of the non-NMDA antagonist CNQX does not affect their firing pattern. These results indicate that, in vivo, excitatory amino acid afferents participate through NMDA receptors in the control of the spontaneous burst firing of midbrain dopamine neurons

The computation of Finite-Frequency kernels without the paraxial approximation

info:eu-repo/semantics/nonPublishe

A new approach to global seismic tomography based on regularization by sparsity in a novel 3D spherical wavelet basis

info:eu-repo/semantics/nonPublishe

Solving or resolving global tomographic models with spherical wavelets, and the scale and sparsity of seismic heterogeneity

info:eu-repo/semantics/nonPublishe

Activation of Brain Noradrenergic Neurons during Recovery from Halothane Anesthesia

International audiencealpha 2-Adrenoceptor agonists, known as antihypertensive agents, may be used during general anesthesia for their anesthetic sparing action and to reduce the occurrence of side effects. Previous studies have shown that the brain's noradrenergic nucleus, locus coeruleus, is an important target in mediating the hypnotic action of alpha 2 agonists. The authors studied the effects of recovery from halothane anesthesia on the electrical activity of locus coeruleus neurons to examine cellular substrates underlying the clinical effectiveness of alpha 2 agonists

Subthalamic nucleus modulates burst firing of nigral dopamine neurones via NMDA receptors

International audienceThe role of the subthalamic nucleus in the burst firing of dopamine neurones of the substantia nigra was investigated using extracellular single unit recordings combined with pressure or iontophoretic micro-injections in anaesthetized rats. Inhibition of subthalamic neurones by pressure injection of gamma-aminobutyric acid (GABA) regularized the burst firing pattern in eight out of 17 dopamine neurones. Bicuculline injection near subthalamic neurones increased their firing rate and increased burst discharge in a subpopulation of dopamine neurones tested (34 out of 102). The increase was depressed by iontophoresis of the N-methyl-D-aspartate (NMDA) antagonist (+-)2-amino,5-phosphonopentanoic acid (AP-5), but not of the non-NMDA antagonist, 6-cyano,7-nitroquinoxaline-2,3-dione (CNQX). These data suggest that the subthalamic nucleus promotes burst discharge in a subpopulation of substantia nigra dopamine neurones via NMDA receptors