Dopamine D4 receptor subtype activation reduces the rat cardiac parasympathetic discharge

García-Pedraza, José Ángel; Morán, Asunción; Martín, María Luisa; Ollauri-Ibáñez, Claudia; Rodríguez-Barbero, Alicia; Villalón, Carlos M.; García-Domingo, Mónica

doi:10.1007/s00424-020-02452-8

Cited by 5 publications

(7 citation statements)

References 42 publications

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“…5E). Of note, at the cardiac level, this isoform modulates the activity of the autonomic nervous system (19). This evidence fits very well with the altered bidirectional heart-brain communication detected in the Granger causality analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Third, the D5 receptor, upregulated in the TGAC8 hippocampus, is one of the primary activators of GABA-A, the main catalyst of gamma activity (15). Accordingly, recent work shows that functional cross-talk exists between GABA-A and D5 in hippocampal neurons, favoring inhibitory current generations (18). Thus, the present results support the novel idea that cardiac dopaminergic signaling shapes heart-to-brain communication through direct endocrine mechanisms (systemic DOPA production) and autonomic ones (D4 modulation on afferent vagal transmission), as well as indirect ones, such as hippocampal upregulation of the D5 receptors.…”

Section: Discussionmentioning

confidence: 99%

“…In aggregate, the new evidence may have the following functional consequences. First, a recent study shows how atrial D4 can modulate vagal activity (19) (i.e., heart-to-brain and brain-to-heart interaction). This fits very well with what we have observed at the level of bidirectional heart-brain communication by Granger analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Third, the D5 receptor, upregulated in the TGAC8 hippocampus, is one of the primary activators of GABA-A, the main catalyst of gamma activity (16). Accordingly, recent work shows that functional cross-talk exists between GABA-A and D5 in hippocampal neurons, favoring inhibitory current generations (19).…”

Section: Dopamine and The Heart-brain Loopmentioning

confidence: 99%

“…The overall model order was applied to the GC estimates of all wake epochs for all mice (both groups). Finally, the validity of the model order was verified by estimating the model consistency (percentage of data correlation structure explained by the model) 19 . Consistency values higher than 75% were considered satisfactory, and all periods had mean consistencies of 90% or above.…”

Section: Brain/heart Communicationmentioning

confidence: 99%

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Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Agrimi

Menicucci

Laurino

et al. 2021

Preprint

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Dopamine and The Heart-brain Loopmentioning

confidence: 99%

Section: Brain/heart Communicationmentioning

confidence: 99%

See 3 more Smart Citations

Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Agrimi

Menicucci

Laurino

et al. 2021

Preprint

View full text Add to dashboard Cite

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Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication

Agrimi,

Menicucci,

et al. 2023

JACC: Clinical Electrophysiology

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State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation

Yang,

Wu,

Zhan

et al. 2024

Front. Neurosci.

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BackgroundVagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance.MethodsWe measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects.Results30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV.Conclusion30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.

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Dopamine D4 receptor subtype activation reduces the rat cardiac parasympathetic discharge

Cited by 5 publications

References 42 publications

Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Cardiac adenylyl cyclase type 8 overexpression increases locomotor activity in mice by modulating EEG-gamma oscillations

Enhanced Myocardial Adenylyl Cyclase Activity Alters Heart-Brain Communication

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation

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