Brain circuits mediating baroreflex bradycardia inhibition in rats: an anatomical and functional link between the cuneiform nucleus and the periaqueductal grey


Corresponding author C. Sévoz-Couche: UPMC/INSERM, UMR-S 975 and CNRS UMR 7225, Faculté de médecine UPMC, Site Pitie-Salpêtrière, 91 bd de l’Hôpital, Paris F-75013, France.  Email:


Non-technical summary  Defence reactions are physiological responses to imminent danger. They include increased blood pressure and heart rate, and a reduction in the reflex cardiac response to changes in blood pressure. Two regions in the brain, the hypothalamus and the periaqueductal grey area, known to be involved in pathological conditions such as anxiety, are involved in the production of these responses. However, there is no direct connection between those regions. In this study we report that the midbrain cuneiform nucleus links the hypothalamus and periaqueductal grey area. Our findings may explain how anxiety is related to cardiovascular pathologies.


Abstract  Defence responses triggered experimentally in rats by stimulation of the dorsomedial nucleus of the hypothalamus (DMH) and the dorsolateral periaqueductal grey matter (PAG) inhibit the cardiac baroreflex response (i.e. bradycardia). It has also been proposed that the midbrain cuneiform nucleus (CnF) is involved in active responses. Our aim was to identify the neurocircuitry involved in defence-induced baroreflex inhibition, with a particular focus on the link between DMH, CnF and dorsolateral PAG. Microinjection of the anterograde tracer Phaseolus vulgaris leucoaggutinin into the CnF revealed a dense projection to the dorsolateral PAG. Moreover, activation of neurons in the CnF induced increased expression of Fos protein in the dorsolateral PAG. Inhibition of neurons of the CnF or dorsolateral PAG prevented the inhibition of baroreflex bradycardia induced by DMH or CnF stimulation, respectively. These results provide a detailed description of the brain circuitry underlying acute baroreflex modulation by neurons of the DMH. Our data have shown for the first time that the CnF plays a key role in defence reaction-associated cardiovascular changes; its stimulation, from the DMH, activates the dorsolateral PAG, which, in turn, inhibits baroreflex bradycardia.