Role of astrocytes in the excitability of magnocelular neurons form supraoptic nucleus during changes in the plasma osmolality

• Grant number: 18/07027-5
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: December 01, 2019
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Melina Pires da Silva
• Grantee: Melina Pires da Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Benedito Honorio Machado
• Associated scholarship(s): 23/18449-6 - Exploring Heterogeneity in Vasopressinergic Neurons of the Supraoptic Nucleus: An Integrated Investigation of Electrical and Genetic Responses, BP.IC; 23/05975-1 - Effect of acute dehydration on astrocytic modulation of magnocellular neurons in the supraoptic nucleus", BP.MS; 19/26034-5 - Role of astrocytes in the excitability of magnocelular neurons form supraoptic nucleus during changes in the plasma osmolality, BP.JP

Abstract

The supraoptic nucleus (SON) represent one of several hypothalamic areas involved in the body fluid balance and play an important role in the complex network of physiological system working to maintain the homeostasis. Since the neurons that constitute this nucleus are intrinsically osmosensitive, they have been designated as a perfect model to study the osmoreceptors. In the last years, experimental evidence has suggested that SON astrocytes can trigger osmoregulatory process and they may be involved in the control of magnocellular neurons excitability. However, little is known about how astrocytes initiate these responses and, if so, how they trigger specialized cellular behaviors related to osmoregulation. In this sense, this project is related to investigate the osmoregulatory mechanisms in order to clarify the influence of astrocytes in the excitability of the magnocellular neurons during increases in the osmolality. In a practical perspective, we intend to use genetically modified animals, in which we will inject a Cre-dependent adeno-associated viral vectors for expression of light-activated cations channels (channelrodopsin), as well as calcium sensors (GCaMP). This technique will allow us to modulate the astrocyte activity with high specificity and temporal accuracy as well as monitoring the activity of calcium ions. Cellular electrophysiology, essentially patch clamp, in the whole cell mode, will be used for recording of electrical activity of interested cells. Both techniques, optogenetics and electrophysiology, will be associated with real time calcium measurements, immunocytochemistry and molecular biology. The expected results should broaden our understanding about the synaptic and biophysical aspects, still unknown, about osmoregulation, especially those related to neurons-astrocytes interaction in the SON. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, MELINA P.; SPILLER, PEDRO F.; PATON, JULIAN F. R.; MORAES, DAVI J. A.. Peripheral chemoreflex activation induces expiratory but not inspiratory excitation of C1 pre-sympathetic neurones of rats. ACTA PHYSIOLOGICA, v. N/A, p. 22-pg., 2022-06-28. (21/06886-7, 19/11863-6, 20/03955-5, 18/07027-5)

SPILLER, PEDRO F.; DA SILVA, MELINA P.; MORAES, DAVI J. A.. Lactate does not activate the carotid body of Wistar rat. Respiratory Physiology & Neurobiology, v. 285, MAR 2021. (16/24869-4, 18/07027-5, 13/10484-5)

MAGALHAES, KAROLYNE S.; DA SILVA, MELINA P.; MECAWI, ANDRE S.; PATON, JULIAN F. R.; MACHADO, BENEDITO H.; MORAES, DAVI J. A.. Intrinsic and synaptic mechanisms controlling the expiratory activity of excitatory lateral parafacial neurones of rats. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 21, OCT 2021. (19/24060-9, 18/15957-2, 19/11863-6, 18/07027-5)

DA SILVA, MELINA P.; MAGALHAES, KAROLYNE S.; DE SOUZA, DANIEL P.; MORAES, DAVI J. A.. Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 6, FEB 2021. (18/15957-2, 19/11863-6, 19/24060-9, 18/07027-5)

MECAWI, ANDRE SOUZA; VARANDA, WAMBERTO ANTONIO; DA SILVA, MELINA PIRES. Osmoregulation and the Hypothalamic Supraoptic Nucleus: From Genes to Functions. FRONTIERS IN PHYSIOLOGY, v. 13, p. 20-pg., 2022-05-24. (18/07027-5, 19/27581-0, 19/26034-5)

MORAES, DAVI J. A.; DA SILVA, MELINA P.; DE SOUZA, DANIEL P.; FELINTRO, VIVIANE; PATON, JULIAN F. R.. Heightened respiratory-parasympathetic coupling to airways in the spontaneously hypertensive rat. JOURNAL OF PHYSIOLOGY-LONDON, v. 599, n. 12, p. 3237-3252, JUN 2021. (19/11863-6, 18/07027-5)