TY - JOUR T1 - Unique Organization of actin cytoskeleton in magnocellular vasopressin neurons in normal conditions and in response to salt-loading JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0351-19.2020 SP - ENEURO.0351-19.2020 AU - Zsuzsanna Barad AU - Suleima Jacob-Tomas AU - Alberto Sobrero AU - Graham Lean AU - Amirah-Iman Hicks AU - Jieyi Yang AU - Katrina Y. Choe AU - Masha Prager-Khoutorsky Y1 - 2020/03/16 UR - http://www.eneuro.org/content/early/2020/03/16/ENEURO.0351-19.2020.abstract N2 - Magnocellular neurosecretory cells are intrinsically osmosensitive and can be activated by increases in blood osmolality, triggering the release of antidiuretic hormone vasopressin (VP) to promote water retention. Hence, the activity of magnocellular VP neurons is one of the key elements contributing to the regulation of body fluid homeostasis in healthy organisms. Chronic exposure to high dietary salt leads to excessive activation of VP neurons, thereby elevating levels of circulating VP, which can cause increases in blood pressure contributing to salt-dependent hypertension. However, the molecular basis underlying high salt diet-induced hyperactivation of magnocellular VP neurons remains not fully understood. Previous studies suggest that magnocellular neurosecretory neurons contain a subcortical layer of actin filaments and pharmacological stabilization of this actin network potentiates osmotically-induced activation of magnocellular neurons. Using super-resolution imaging in situ, we investigated the organization of the actin cytoskeleton in rat magnocellular neurosecretory cells under normal physiological conditions and after a chronic increase in blood osmolality following 7 days of salt-loading. We found that, in addition to the subcortical layer of actin filaments, magnocellular VP neurons are endowed with a unique network of cytoplasmic actin filaments throughout their somata. Moreover, we revealed that the density of both subcortical and cytoplasmic actin networks in magnocellular VP neurons is dramatically increased following salt-loading. These results suggest that increased osmo-responsiveness of VP neurons following chronic exposure to high dietary salt may be mediated by the modulation of unique actin networks in magnocellular VP neurons, possibly contributing to elevated blood pressure in this condition.Significance statement: Hypothalamic magnocellular neurons secrete antidiuretic hormone vasopressin into the circulation, promoting vasoconstriction and renal water retention. Regulation of vasopressin secretion is a key factor controlling body fluid homeostasis, and excessive vasopressin secretion contributes to fluid balance disorders such as salt-sensitive hypertension. Using super-resolution analysis of different areas of the rat brain, we show that vasopressin neurons feature a unique actin cytoskeleton comprising a subcortical actin layer and an array of cytoplasmic comet-like structures, which are not present in any other neuronal cell type. Moreover, the density of these unique actin structures is increased in a rodent model of salt-sensitive hypertension, and our findings suggest that this modification may contribute to excessive activation of vasopressin neurons in a model salt-sensitive hypertension. ER -