RT Journal Article
SR Electronic
T1 Cardiac-generated sympathetic stress alters heart-brain communication, reduces EEG-theta activity, and increases locomotor behavior
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.19.452502
DO 10.1101/2021.07.19.452502
A1 Jacopo Agrimi
A1 Danilo Menicucci
A1 Marco Laurino
A1 Chelsea D Mackey
A1 Laila Hasnain
A1 Sneha Dodaballapur
A1 Ross A McDevitt
A1 Donald B Hoover
A1 Angelo Gemignani
A1 Nazareno Paolocci
A1 Edward G Lakatta
YR 2021
UL http://biorxiv.org/content/early/2021/07/20/2021.07.19.452502.abstract
AB Brain modulation of myocardial activity via the autonomic nervous system is increasingly well characterized. Conversely, how primary alterations in cardiac function, such as an intrinsic increase in heart rate or contractility, reverberate on brain signaling/adaptive behaviors - in a bottom-up modality - remains largely unclear. Mice with cardiac-selective overexpression of adenylyl cyclase type 8 (TGAC8) display increased heart rate and reduced heart rhythm complexity associated with a nearly abolished response to external sympathetic inputs. Here, we tested whether chronically elevated intrinsic cardiac performance alters the heart-brain informational flow, affecting brain signaling and, thus, behavior. To this end, we employed dual lead telemetry for simultaneous recording of EEG and EKG time series in awake, freely behaving TGAC8 mice and wild-type (WT) littermates. We recorded EEG and EKG signals, while monitoring mouse behavior with established tests. Using heart rate variability (HRV) in vivo and isolated atria response to sympathomimetic agents, we first confirmed that the TGAC8 murine heart evades autonomic control. The EEG analysis revealed a substantial drop in theta-2 (4-7 Hz) activity in these transgenic mice. Next, we traced the informational flow between EKG and EEG in the theta-2 frequency band via the Granger causality statistical approach and we found a substantial decrement in the extent of heart/brain bidirectional communication. Finally, TGAC8 mice displayed heightened locomotor activity in terms of behavior, with higher total time mobile, distance traveled, and movement speed while freezing behavior was reduced. Increased locomotion correlated negatively with theta-2 waves count and amplitude. Our study shows that cardiac-born persistent sympathetic stress disrupts the information flow between the heart and brain while influencing central physiological patterns, such as theta activity that controls locomotion. Thus, cardiac-initiated disorders, such as persistently elevated cardiac performance that escapes autonomic control, are penetrant enough to alter brain functions and, thus, primary adaptive behavioral responses.Competing Interest StatementThe authors have declared no competing interest.