Respiratory and sleep effects produced by pharmacogenetic stimulation of the pedunculopontine tegmental nucleus that project to the lateral parabrachial nucleus

• Grant number: 18/12834-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: February 01, 2019
• End date: January 31, 2020
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Thiago dos Santos Moreira
• Grantee: Janayna Dias Lima
• Supervisor: Clifford Saper
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 17/01380-2 - Pedunculo pontine tegmental nucleus and brainstem respiratory interactions in breathing, BP.DD

Abstract

The pedunculopontine tegmental nucleus (PPTg) is considered an important nucleus in the mesopontine region and has been shown to have important functions. These neurons exhibit wake- and REM-dependent firing behavior maintenance of the sleep-wake state and are known to participate in a wide range of state-regulating functions including control of breathing. Previous works demonstrate the efferent projections of PPTg neurons, these projections are varied and may influence cortical activity and sleep/wake states. Results from our laboratory showed that glutamatergic stimulation of PPTg was able to increase the respiratory activity, whereas cholinergic stimulation was able to reduce respiratory activity. Our neuroanatomical data showed that the PPTg has projection to several regions of the brainstem, among them the retrotrapezoid nucleus, raphe pallidus, Kölliker Fuse (KF) and lateral parabrachial nucleus (LPBN) complex. The LPBN is very important for sensory information to the amygdala, thalamus, hypothalamus and other nuclei and has efferent projections that innervate neurons involved in respiratory control. Studies have shown that LBPN is important for the hypercapnia or hypoxia ventilatory responses and is also involved in wakefulness response to CO2. Therefore, our hypothesis is that PPTg neurons may be important for transmitting signals to the lateral parabrachial nucleus region and modulate cardiorespiratory activity. The goal of this study is evaluate in non-anesthetized mice whether the selective activation of the PPTg neurons with projection to the lateral parabrachial nucleus (LPBN) produce respiratory changes and whether these alterations are dependent on any specific state of brain activity. That study will be identify key components of the neural pathway involved in breathing control, providing also framework for understanding the molecular basis of state dependent control of breathing. (AU)