Kainate Receptor-Induced Retrograde Inhibition of Glutamatergic Transmission in Vasopressin Neurons

Abstract

Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter release. We here report that applications of agonists of GluK1-containing KARs in the rat supraoptic nucleus has an opposite action on glutamatergic transmission according to the phenotype of the postsynaptic neuron. Whereas glutamate release was facilitated in oxytocin (OT) neurons, it was inhibited in vasopressin (VP) cells. Interestingly, an antagonist of GluK1-containing KARs caused an inhibition of glutamate release in both OT and VP neurons, revealing the existence of tonically activated presynaptic KARs that are positively coupled to transmitter release. We thus postulated that the inhibition of glutamate release observed with exogenous applications of GluK1 agonists on VP neurons could be indirect. In agreement with this hypothesis, we first showed that functional GluK1-containing KARs were present postsynaptically on VP neurons but not on OT cells. We next showed that the inhibitory effect induced by exogenous GluK1 receptor agonist was compromised when BAPTA was added in the recording pipette to buffer intracellular Ca 2ϩ and block the release of a putative retrograde messenger. Under these conditions, GluK1-containing KAR agonist facilitates glutamatergic transmission in VP neurons in a manner similar to that observed for OT neurons and that resulted from the activation of presynaptic GluK1 receptors. GluK1-mediated inhibition of glutamate release in VP neurons was also blocked by a -opioid receptor antagonist. These findings suggest that activation of postsynaptic GluK1-containing KARs on VP neurons leads to the release of dynorphin, which in turn acts on presynaptic -opioid receptors to inhibit glutamate release.

Electrophysiological Effects of Kainic Acid on Vasopressin‐Enhanced Green Fluorescent Protein and Oxytocin‐Monomeric Red Fluorescent Protein 1 Neurones Isolated from the Supraoptic Nucleus in Transgenic Rats

“…A previous study showed that presynaptic glutamate release was facilitated in OXT neurones by ATPA but was inhibited in AVP neurones . By contrast, AVP neurones (but not OXT neurones) express functional postsynaptic GluK1‐containing KARs . Unexpectedly, our results demonstrated that GluK1‐containing KARs are expressed in both AVP‐eGFP and OXT‐mRFP1 neurones.…”

“…A previous study showed that presynaptic glutamate release was facilitated in OXT neurones by ATPA but was inhibited in AVP neurones . By contrast, AVP neurones (but not OXT neurones) express functional postsynaptic GluK1‐containing KARs .…”

“…It is known that the GluK1 and GluK5 (but not GluK2, GluK3 or GluK4) subunit mRNAs are expressed in rat SON neurones . Recently, a study assessed presynaptic responses to KA in SON neurones using rat brain slice preparations . In that study, GluK1‐containing KARs were found to be present post synaptically in AVP neurones but not in OXT neurones.…”

Extracellular signal‐regulated kinase phosphorylation in forebrain neurones contributes to osmoregulatory mechanisms

“…After recording, magnocellular neurones filled with biocytin (0.1%) were identified further by immunocytochemistry as previously described (Bonfardin et al 2012). At the end of the recording period, slices were fixed by immersion in 4% paraformaldehyde and 0.15% picric acid (2 h, room temperature and during 2 or 3 days at 4°C).…”