PreBötzinger complex neurons drive respiratory modulation of blood pressure and 1 heart rate 2 3

Clément Menuet (1, 2) , Angela A Connelly (2) , Jaspreet K Bassi (2) , Mariana R Melo (2) , Sheng Le (3) , Jessica Kamar (2) , Natasha N Kumar (4) , Stuart J Mcdougall (5) , Simon Mcmullan (3) , Andrew E Allen (2, 5)

1 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
2 Victoria University [Melbourne]
3 Macquarie University
4 UNSW - University of New South Wales [Sydney]
5 Florey Inst Neurosci & Mental Hlth,

18 Heart rate and blood pressure oscillate in phase with respiratory activity. A component of 19 these oscillations is generated centrally, with respiratory neurons entraining the activity of 20 pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of 21 optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we 22 demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for 23 inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, 24 inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst 25 excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating 26 heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more 27 functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory 28 oscillations. The findings have implications for cardiovascular pathologies, such as 29 hypertension and heart failure, where respiratory entrainment of heart rate is diminished and 30 respiratory entrainment of blood pressure exaggerated. 31 32

Mots clés: preBötzinger complex; master oscillator; cardiorespiratory control; respiratory 33 sinus arrhythmia; respiratory-sympathetic modulation; optogenetic inhibition; GtACR2 34

Domaines: Neurosciences [q-bio.NC]; Physiologie [q-bio.TO]

Clément Menuet, Angela A Connelly, Jaspreet K Bassi, Mariana R Melo, Sheng Le, et al.. PreBötzinger complex neurons drive respiratory modulation of blood pressure and 1 heart rate 2 3. eLife, In press. ⟨hal-02879307⟩