GABA Receptor Control of Parasympathetic Outflow to Heart: Characterization and Brainstem Localization

DiMicco, Joseph A.; Gale, Karen; Hamilton, Betty L.; Gillis, Richard A.

doi:10.1126/science.451556

Cited by 144 publications

(46 citation statements)

References 16 publications

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“…For example, injection of a GABA receptor antagonist into the nucleus ambiguous of the brainstem shows a dose-dependent decrease in heart rate and blood pressure. This effect does not occur in any other areas of the brainstem, suggesting that GABA inhibits vagal outflow from the nucleus ambiguous (DiMicco et al 1979). Inspiratory-modulated GABAergic neurons may be responsible for the inhibition of parasympathetic cardioinhibitory neurons that result in respiratory sinus arrhythmia (Frank and Mendelowitz 2012).…”

Section: Possible Role Of Membrane Potential In Cardiorespiratory Modmentioning

confidence: 90%

Self-Regulation of Breathing as a Primary Treatment for Anxiety

Jerath¹,

Crawford²,

Barnes

et al. 2015

Appl Psychophysiol Biofeedback

187

125

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Understanding the autonomic nervous system and homeostatic changes associated with emotions remains a major challenge for neuroscientists and a fundamental prerequisite to treat anxiety, stress, and emotional disorders. Based on recent publications, the inter-relationship between respiration and emotions and the influence of respiration on autonomic changes, and subsequent widespread membrane potential changes resulting from changes in homeostasis are discussed. We hypothesize that reversing homeostatic alterations with meditation and breathing techniques rather than targeting neurotransmitters with medication may be a superior method to address the whole body changes that occur in stress, anxiety, and depression. Detrimental effects of stress, negative emotions, and sympathetic dominance of the autonomic nervous system have been shown to be counteracted by different forms of meditation, relaxation, and breathing techniques. We propose that these breathing techniques could be used as firstline and supplemental treatments for stress, anxiety, depression, and some emotional disorders.

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Section: Possible Role Of Membrane Potential In Cardiorespiratory Modmentioning

confidence: 90%

Self-Regulation of Breathing as a Primary Treatment for Anxiety

Jerath¹,

Crawford²,

Barnes

et al. 2015

Appl Psychophysiol Biofeedback

187

125

View full text Add to dashboard Cite

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“…In vivo studies show that microinjection of bicuculline into the nucleus ambiguus of the brainstem produces a decrease in the heart rate and blood pressure that is mediated by the vagus nerve (DiMicco et al, 1979). This indicates that the nucleus ambiguus is a site of GABA receptormediated inhibition of vagal outflow to the heart (DiMicco et al, 1979;Williford et al, 1980). In vitro studies reflect this by demonstrating that cardiac vagal neurons in the nucleus ambiguus are constantly inhibited by spontaneous GABAergic synaptic input; one likely GABAergic pathway may arise from the NTS (Wang et al, 2001a).…”

Section: Discussionmentioning

confidence: 99%

“…Most parasympathetic activity regulating heart rate and cardiac function originates from central parasympathetic cardiac neurons within the nucleus ambiguus (Mendelowitz, 1999;Wang et al, 2001a,b). Recent studies have re-vealed two major synaptic inputs to cardiac vagal neurons from the NTS: an excitatory glutamatergic pathway (Mendelowitz, 1998;Neff et al, 1998b) and an inhibitory GABAergic input (DiMicco et al, 1979;Wang et al, 2001a,b). Nicotine has also been found to facilitate glutamatergic transmission, as well as to directly activate vagal cardioinhibitory neurons (Neff et al, 1998a (Sim and Childers, 1997), in situ hybridization, and immunohistochemistry (Neal et al, 1999a,b;Houtani et al, 2000;Mollereau and Mouledous, 2000) have identified both ORL 1 receptors (Sim and Childers, 1997;Neal et al, 1999a;Houtani et al, 2000;Mollereau and Mouledous, 2000) and nociceptin itself (Neal et al, 1999b) within the NTS and nucleus ambiguus.…”

mentioning

confidence: 99%

Nociceptin Inhibits γ-Aminobutyric Acidergic Inputs to Cardiac Parasympathetic Neurons in the Nucleus Ambiguus

Venkatesan

Wang²,

Evans³

et al. 2002

J Pharmacol Exp Ther

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Studies have shown that nociceptin, the endogenous ligand for the opioid receptor-like receptor (ORL 1 ), modulates central control of cardiovascular activity. The nucleus ambiguus, an area containing cardiac parasympathetic neurons, contains both ORL 1 receptors and neurons that contain nociceptin itself. Although previous work has shown that nociceptin acts to increase parasympathetic outflow to the heart, the mechanisms by which this is achieved are unknown. In the present study, the effects of nociceptin on spontaneous ␥-aminobutyric acidergic (GABAergic) input to cardiac parasympathetic neurons (IPSCs) was examined. At 100 M, nociceptin inhibited both the frequency (Ϫ35.6%) and the amplitude (Ϫ49.5%) of spontaneous GABAergic IPSCs in cardiac vagal neurons. Nociceptin also caused a novel postsynaptic inhibition of the responses evoked by exogenous application of GABA. These results indicate that nociceptin acts both on neurons precedent to cardiovascular neurons to decrease the activity of GABAergic neurons that synapse upon cardiovascular neurons and directly, inhibiting the postsynaptic currents evoked by GABA. This inhibition by nociceptin would increase parasympathetic outflow to the heart, thus providing a possible mechanism for nociceptininduced bradycardia.Nociceptin, a newly discovered endogenous peptide, is the ligand for the opioid receptor-like receptor (ORL 1 ) (Henderson and McKnight, 1997;Meunier, 1997). Despite its selective binding to this receptor, nociceptin shares a structural resemblance to classical endogenous opioid peptides and displays actions in common with them, including modulation of pain (Henderson and McKnight, 1997;King et al., 1997) and cellular actions such as inhibition of synaptic transmission (Emmerson and Miller, 1999); regulation of neurotransmitter release including serotonin (Siniscalchi et al

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“…Premotor cardiac vagal neurons are located in the nucleus ambiguus and the dorsal motor nucleus of the vagus (DiMicco et al 1979;Mendelowitz 1999Mendelowitz , 1996Standish et al 1995;Stuesse 1982). Since premotor cardiac vagal neurons are intrinsically silent, their activity is determined by excitatory and inhibitory synaptic inputs (Mendelowitz 1999(Mendelowitz , 1996Mendelowitz and Kunze 1991).…”

Section: Introductionmentioning

confidence: 99%