Oxitocinergic signaling of ventral surface chemoreceptors neurons

• Grant number: 22/15609-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): May 01, 2023
• Effective date (End): April 30, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Emmanuel Veríssimo de Araújo
• Supervisor: Daniel Kent Mulkey
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: University of Connecticut (UCONN), United States
• Associated to the scholarship: 20/08620-1 - Hypothalamus and retrotrapezoid nucleus interaction in the control of breathing activity, BP.DR

Abstract

Respiratory activity is maintained unconsciously by the activity of respiratory chemoreceptors, including those located in the retrotrapezoid nucleus (RTN), which control respiratory output in response to changes in tissue CO2/H+. Despite the importance of RTN chemoreceptors, we still do not know about the mechanisms that support their activity, particularly the neuromodulation involving several hypothalamic hormones such as oxytocin (Oxt). The RTN receives hypothalamic inputs and a longstanding hypothesis contends that oxytocinergic neurotransmission is a requisite component of breathing. Despite this potentially important physiological role, almost nothing is known about the mechanisms underlying the oxytocinergic modulation of brainstem respiratory neurons. Evidence does suggest that Oxt modulates respiratory neurons by activation of Oxt receptors, although the signalling molecules and downstream ion channel targets contributing to this response are entirely unknown.Therefore, in the present project, at the cellular level, we will investigate how chemosensitive RTN neurons are activated by Oxt, and this response could be reduced by blockers of Oxt receptor. We will also test if the function of RTN neurons as chemoreceptors will be dependent on oxytocinergic signalling. Furthermore, we will investigate if Oxtsensitivity could be reduced by blocking inositol 1,4,5trisphosphate (IP3) receptors, depleting intracellular Ca2+ stores, inhibiting CK2. We believe that our data will identify a new component of the signalling pathway that couple oxytocinergic receptor activation to changes in chemoreceptor excitability. (AU)