Advances in the neurophysiology of magnocellular neuroendocrine cells

Abstract

Hypothalamic magnocellular neuroendocrine cells have unique electrical proper-ties and a remarkable capacity for morphological and synaptic plasticity. Their large somatic size, their relatively uniform and dense clustering in the supraoptic and paraventricular nuclei, and their large axon terminals in the neurohypophysis make them an attractive target for direct electrophysiological interrogation. Here, we provide a brief review of significant recent findings in the neuroplasticity and neurophysiological properties of these neurones that were presented at the symposium "Electrophysiology of Magnocellular Neurons" during the 13th World Congress on Neurohypophysial Hormones in Ein Gedi, Israel in April 2019. Magnocellular vasopressin (VP) neurones respond directly to hypertonic stimulation with membrane depolarisation, which is triggered by cell shrinkage-induced opening of an N-terminaltruncated variant of transient receptor potential vanilloid type-1 (TRPV1) channels.New findings indicate that this mechanotransduction depends on actin and microtubule cytoskeletal networks, and that direct coupling of the TRPV1 channels to microtubules is responsible for mechanical gating of the channels. Vasopressin neurones also respond to osmostimulation by activation of epithelial Na + channels (ENaC). It was shown recently that changes in ENaC activity modulate magnocellular neurone basal firing by generating tonic changes in membrane potential. Both oxytocin and VP neurones also undergo robust excitatory synapse plasticity during chronic osmotic stimulation. Recent findings indicate that new glutamate synapses induced during chronic salt loading express highly labile Ca 2+ -permeable GluA1 receptors requiring continuous dendritic protein synthesis for synapse maintenance. Finally, recordings from the uniquely tractable neurohypophysial terminals recently revealed an unexpected property of activity-dependent neuropeptide release. A significant fraction of the voltage-dependent neurohypophysial neurosecretion was found to be independent of Ca 2+ influx through voltage-gated Ca 2+ channels. Together, these findings provide a snapshot of significant new advances in the electrophysiological signalling mechanisms and neuroplasticity of the hypothalamic-neurohypophysial system, a system that continues to make important contributions to the field of neurophysiology.

Voltage‐induced Ca2+release by ryanodine receptors causes neuropeptide secretion from nerve terminals

“…The evidence stated above makes it plausible that increases in [Ca 2+ ] i are a result of RyR in the NSG membrane, 29,30 and that these localised Ca 2+ release events might play a role in the modulation of secretion, either as a result of activation of RyR via depolarisation, or via a CICR‐like mechanism (see Fig. 7 in 73 ).…”

“…Ca 2+ release from internal stores evoked by depolarisation or CICR may provide another important source of Ca 2+ for this process (see Fig. 7 in 73 ).…”

“…The other half of such secretion could be a result of calcium‐independent voltage‐dependent neuropeptide secretion or CIVDS (see Fig. 7 in 73 ).…”

Participation of TRPV1 in the activity of the GnRH system in male rats

“…Regarding TRPV1 modulation on Kiss1 and Gnrh levels, there are no previous reports studying its participation on the synthesis or release of reproductive neuropeptides. Hypothalamic expression of TRPV1 was shown to be present in the paraventricular nuclei (Brown, Bains, Ludwig, & Stern, 2013), whereas vasopressin and oxytocin neurons, which possess N terminal‐truncated TRPV1 channels (Tasker, Prager‐Khoutorsky, Teruyama, Lemos, & Amstrong, 2020), are known to be located in the aforementioned nucleus and participate in GnRH and kisspeptidergic control (Williams, Jarjisian, Mikkelsen, & Kriegsfeld, 2011; Yeo & Colledge, 2018; Zhu, Zhao, Huang, Wang, & Wang, 2019). Therefore, vasopressin and oxytocin neurons could mediate the effects of TRPV1 on Kiss1 modulation.…”

Advances in neurohypophysial hormones research

“…The special issue comprises reviews and original research articles covering basic aspects of the OXT and AVP systems, including neuroanatomy, neuropeptide release, gene expression, and physiological and behavioural outputs. The issue opens with a review by Tasker and colleagues on past and recent advances in the neurophysiology of magnocellular neuroendocrine neurones, including selected studies that were presented at the symposium “Electrophysiology of Magnocellular Neurons” within WCNH2019 4 . A second review by Lawson and colleagues describes the physiological role of OXT in the regulation of energy balance 5 .…”