Compartment-specific calcium dynamics and their role in somatodendritic exocytosis and autoregulation of vasopressin neurons

Abstract

Vasopressin (VP) neurons exhibit somatodendritic release (SDR) of their neuropeptide cargo, in addition to axonal release. The phasic firing of these neurons dictates the volume and pattern of this exocytosis. This phasic patterning and SDR are dependent on intracellular changes in Ca2+ (Δ[Ca2+]i). When SDR occurs, VP acts in an autocrine manner to inhibit VP firing activity via activation of V1aR-mediated increases in [Ca2+]i. Because SDR and subsequent autoinhibition are dictated by Δ[Ca2+]i, we investigated whether this Ca2+-dependent inhibition involved afterhyperpolarizations (AHPs) and how compartment-specific Ca2+ dynamics affected neuronal properties. Using a combination of patch clamp electrophysiology, simultaneous Ca2+ imaging, and targeted photolytic uncaging, we investigated the properties of Ca2+ spread in soma and dendrites of VP magnocellular neurons of supraoptic nucleus (SON). We found that whereas Ca2+ uncaging in soma efficiently invades dendrites, dendritic Ca2+ uncaging fails to propagate into the soma, supporting unidirectional Ca2+ movement between cellular compartments. Moreover, we found that Ca2+ uncaging in the soma but not dendrites evoked AHPs, indicating compartmental localization of AHP mechanisms and/or channels. Blockade of mitochondrial Ca2+ reuptake (Ru360 in the pipette) prolongs Δ[Ca2+]i elevations and AHPs triggered by Ca2+ uncaging, indicating that mitochondria in VP neurons plays an important role in shaping Ca2+ dynamics and AHP properties in these neurons. Consistent with previous reports, we found that bath application of VP (1 μM) inhibits VP neuronal activity. Moreover, we found that VP enhances the apamin-insensitive slow AHP by prolonging its duration but not its amplitude, whereas a V1aR antagonist SR49059 (1 μM) per se inhibits slow AHPs in these neurons. These results expose vital aspects of the mechanisms that dictate phasic firing, SDR, and the autoinhibitory nature of VP in SON. NHLBI F32HL158172 (MKK), NHLBI HL090948 (JES), NINDS NS094640 (JES) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.