A long-lasting calcium-activated nonselective cationic current is generated by synaptic stimulation or exogenous activation of group I metabotropic glutamate receptors in CA1 pyramidal neurons.

International audienceWe have shown previously that a selective metabotropic glutamate receptor (mGluR) agonist, 1S,3R-1-aminocyclo-pentane-1, 3-dicarboxylate (1S,3R-ACPD), evokes an inward current in CA1 pyramidal neurons of rat hippocampal slices in the presence of K+ channel blockers (). This current has been characterized as a Ca2+-activated nonselective cationic (CAN) current. Using whole-cell patch-clamp recordings and intracellular dialysis, we now have identified the mGluR subtype and the mechanisms underlying the CAN current (ICAN) and report for the first time the presence of a synaptic ICAN in the mammalian CNS. First, we have shown pharmacologically that activation of ICAN by 1S,3R-ACPD involves the group I mGluRs (and not the groups II and III) and a G-protein-dependent process. We also report that ICAN is modulated by the divalent cations (Mg2+, Cd2+, and Zn2+). Second, we have isolated a slow synaptic inward current evoked by a high-frequency stimulation in the presence of K+ channel blockers, ionotropic glutamate, and GABAA receptor antagonists. This current shows similar properties to the exogenously evoked ICAN: its reversal potential is close to the reversal potential of the 1S, 3R-ACPD-evoked ICAN, and it is G-protein- and Ca2+-dependent. Because the amplitude and duration of ICAN increased in the presence of a glutamate uptake blocker, we suggest that this synaptic current is generated via the activation of mGluRs. We propose that the synaptic ICAN, activated by a brief tetanic stimulation and leading to a long-lasting inward current, may be involved in neuronal plasticity and synchronized network-driven oscillations

Endothelin uncouples gap junctions in sustentacular cells and olfactory ensheathing cells of the olfactory mucosa.

International audienceSeveral factors modulate the first step of odour detection in the rat olfactory mucosa (OM). Among others, vasoactive peptides such as endothelin might play multifaceted roles in the different OM cells. Like their counterparts in the central nervous system, the olfactory sensory neurons are encompassed by different glial-like non-neuronal OM cells; sustentacular cells (SCs) surround their cell bodies, whereas olfactory ensheathing cells (OECs) wrap their axons. Whereas SCs maintain both the structural and ionic integrity of the OM, OECs assure protection, local blood flow control and guiding of olfactory sensory neuron axons toward the olfactory bulb. We previously showed that these non-neuronal OM cells are particularly responsive to endothelin in vitro. Here, we confirmed that the endothelin system is strongly expressed in the OM using in situ hybridization. We then further explored the effects of endothelin on SCs and OECs using electrophysiological recordings and calcium imaging approaches on both in vitro and ex vivo OM preparations. Endothelin induced both robust calcium signals and gap junction uncoupling in both types of cells. This latter effect was mimicked by carbenoxolone, a known gap junction uncoupling agent. However, although endothelin is known for its antiapoptotic effect in the OM, the uncoupling of gap junctions by carbenoxolone was not sufficient to limit the cellular death induced by serum deprivation in OM primary culture. The functional consequence of the endothelin 1-induced reduction of the gap junctional communication between OM non-neuronal cells thus remains to be elucidated

Modulation des réponses aux odorants de la muqueuse olfactive de rat par les peptides métaboliques : focus sur le NPY

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Neuropeptide Y modulates olfactory mucosa responses to odorant in fasted rat

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Permanent reduction of seizure threshold in post-ischemic CA3 pyramidal neurons.

International audienceThe effects of ischemia were examined on CA3 pyramidal neurons recorded in hippocampal slices 2-4 mo after a global forebrain insult. With intracellular recordings, CA3 post-ischemic neurons had a more depolarized resting membrane potential but no change of the input resistance, spike threshold and amplitude, fast and slow afterhyperpolarization (AHP) or ADP, and firing properties in response to depolarizing pulses. With both field and whole-cell recordings, synaptic responses were similar in control and post-ischemic neurons. Although there were no spontaneous network-driven discharges, the post-ischemic synaptic network had a smaller threshold to generate evoked and spontaneous synchronized burst discharges. Thus lower concentrations of convulsive agents (kainate, high K(+)) triggered all-or-none network-driven synaptic events in post-ischemic neurons more readily than in control ones. Also, paired-pulse protocol generates, in post-ischemics but not controls, synchronized field burst discharges when interpulse intervals ranged from 60 to 100 ms. In conclusion, 2-4 mo after the insult, the post-ischemic CA3 pyramidal cells are permanently depolarized and have a reduced threshold to generate synchronized bursts. This may explain some neuropathological and behavioral consequences of ischemia as epileptic syndromes observed several months to several years after the ischemic insult

Endothelin impacts on olfactory processing in rats

International audienceIn the olfactory epithelium, olfactory sensitive neurons and their axons are surrounded by glia-like cells called sustentacular cells, which maintain both the structural and ionic integrity of the olfactory mucosa. We have previously found that endothelin-1 (ET-1) can uncouple sustentacular cell gap junctions in vitro similarly as carbenoxolone, a known gap junction uncoupling agent. The role of gap junctions in odorant transduction remains controversial and we explored here if ET-1 naturally produced by the olfactory mucosa could impact odorant detection. Using calcium imaging on olfactory mucosa explant, we first confirmed that ET-1 uncouples gap junctions in an olfactory mucosa preparation preserving the tissue integrity. We next measured the olfactory epithelium responses to odorant stimulation using electro-olfactogram recordings. While the amplitude of the response was not modified by application of ET-1 and carbenoxolone, its repolarizing phase was slower after both treatments. We finally examined the behavioral performances of rat pups in an orientation test based on maternal odor recognition after intranasal instillations of ET-1 or carbenoxolone. While rat pups performances were decreased after ET-1 treatment, it was unchanged after carbenoxolone treatment. Overall, our results indicate that ET-1 modulates olfactory responses at least partly through gap junction uncoupling