title: Modulation of spike clustering by NMDA receptors and neurotensin in rat supraoptic nucleus neurons.
abstract: Magnocellular neurosecretory cells (MNCs) in the rat supraoptic nucleus display clustered firing during hyperosmolality or dehydration. This response is beneficial because this type of activity potentiates vasopressin secretion from axon terminals in the neurohypophysis and thus promotes homoeostatic water reabsorption from the kidney. However, the mechanisms which lead to the generation of clustering activity in MNCs remain unknown. Previous work has shown that clustered firing can be induced in these neurons through the pharmacological activation of NMDA receptors (NMDARs) and that silent pauses observed during this activity are mediated by apamin-sensitive calcium activated potassium (SK) channels. However, it remains unknown if clustered firing can be induced in situ by endogenous glutamate release from axon terminals. Here we show that electrical stimulation of glutamatergic osmosensory afferents in the organum vasculosum lamina terminalis (OVLT) can promote clustering in MNCs via NMDARs and apamin-sensitive channels.We also show that the rate of spike clustering induced by NMDA varies as a bell-shaped function of voltage, and that partial inhibition of SK channels can increase cluster duration and reduce the rate of clustering. Finally,we show that MNCs express neurotensin type 2 receptors, and that activation of these receptors can simultaneously depolarize MNCs and suppress clustered firing induced by bath application of NMDA or by repetitive stimulation of glutamate afferents. These studies reveal that spike clustering can be induced in MNCs by glutamate release from afferent nerve terminals and that that this type of activity can be fine-tuned by neuromodulators such as neurotensin.
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4.
authors: Ariane
authors: A
authors: Gagnon
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4.
authors: Michael
authors: M
authors: Walsh
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4.
authors: Tika
authors: T
authors: Okuda
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4.
authors: Katrina Y
authors: KY
authors: Choe
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4.
authors: Cristian
authors: C
authors: Zaelzer
authors: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal QC, Canada H3G 1A4 charles.bourque@mcgill.ca.
authors: Charles W
authors: CW
authors: Bourque
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D004558:Electric Stimulation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000378:metabolism; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: C099727:Ntsr2 protein, rat; D016194:Receptors, N-Methyl-D-Aspartate; D018028:Receptors, Neurotensin; D009496:Neurotensin