Optogenetic stimulation of locus ceruleus neurons augments inhibitory transmission to parasympathetic cardiac vagal neurons via activation of brainstem α1 and β1 receptors
Open accessAbstract
Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 ± 8% (p = 0.003, n = 26) and augmented GABAergic IPSCs in CVNs by 21 ± 5% (p = 0.001, n = 26). Inhibiting α1, but not α2, receptors blocked the evoked responses. Inhibiting β1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, α1 and/or β1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.
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Activity in the LC-NE system is accompanied by excitatory effects on cardiac muscles resulting in activation of the SNS and deactivation of the PNS.
“studies have shown that activity in the LC-NE system is accompanied by excitatory effects on cardiac muscles resulting in activation of the SNS (Wang et al., 2014) and deactivation of the PNS (Samuels and Szabadi, 2008),”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Wang et al., 2014
The Discussion reports that LC stimulation has been associated with increased heart rate, supporting the claimed cardiac effect. But Wang et al. explain their finding through inhibition of parasympathetic cardiac vagal neurons; the cited passages do not establish sympathetic nervous system activation or direct excitation of cardiac muscle. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThere is a direct relationship between HR and LC activity.
“demonstrating a direct relationship between HR and LC activity.”
From Is autonomic nervous system function atypical in Attention Deficit Hyperactivity Disorder (ADHD)? A systematic review of the evidence (2020) · cites this paper as Wang et al., 2014
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Cites
Aston-Jones, G., & Cohen, J. D. (2005) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135709 · Cited by 4,472 · see citing works
Aston-Jones, G., & Bloom, F. (1981) · The Journal of Neuroscience · doi:10.1523/jneurosci.01-08-00876.1981 · Cited by 1,960 · see citing works
A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing
Madisen, L., Mao, T., Koch, H., Zhuo, J.-M., Berenyi, A., Fujisawa, S., Hsu, Y.-W. A., Garcia, A. J., Gu, X., Zanella, S., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3078 · Cited by 1,398 · see citing works
Aston-Jones, G., & Bloom, F. (1981) · Journal of Neuroscience · doi:10.1523/jneurosci.01-08-00887.1981 · Cited by 1,033 · see citing works
Tuning arousal with optogenetic modulation of locus coeruleus neurons
Carter, M. E., Yizhar, O., Chikahisa, S., Nguyen, H., Adamantidis, A., Nishino, S., Deisseroth, K., & de Lecea, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2682 · Cited by 993 · see citing works
Neuronal excitability modulation over the sleep cycle: a structural and mathematical model
McCarley, R. W., & Hobson, J. (1975) · Science · doi:10.1126/science.1135627 · Cited by 652 · see citing works
Adaptive gain and the role of the locus coeruleus–norepinephrine system in optimal performance
Aston‐Jones, G., & Cohen, J. D. (2005) · The Journal of Comparative Neurology · doi:10.1002/cne.20723 · Cited by 630 · see citing works
Stress-related noradrenergic activity prompts large-scale neural network reconfiguration
Hermans, E. J., van Marle, H. J. F., Ossewaarde, L., Henckens, M. J. A. G., Qin, S., van Kesteren, M. T. R., Schoots, V. C., Cousijn, H., Rijpkema, M., Oostenveld, R., et al. (2011) · Science · doi:10.1126/science.1209603 · Cited by 627 · see citing works
Aston‐Jones, G., Chiang, C., & Alexinsky, T. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63830-3 · Cited by 589 · see citing works
Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology
Aston‐Jones, G., Shipley, M., Chouvet, G., Ennis, M. J., Bockstaele, E. V., Pieribone, V. A., Shiekhattar, R., Akaoka, H., Drolet, G., Astier, B., et al. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)63799-1 · Cited by 543 · see citing works
On the projections from the locus coeruleus noradrenaline neurons: The cerebellar innervation
Olson, L., & Fuxé, K. (1971) · Brain Research · doi:10.1016/0006-8993(71)90533-6 · Cited by 497 · see citing works
Nygren, L.-G., & Olson, L. (1977) · Brain Research · doi:10.1016/0006-8993(77)90707-7 · Cited by 497 · see citing works
Potential clinical relevance of the “little brain” on the mammalian heart
Armour, J. A. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2007.041178 · Cited by 417 · see citing works
Noradrenergic modulation of arousal
Berridge, C. W. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.013 · Cited by 368 · see citing works
Neural organisation and control of the baroreceptor reflex
Spyer, K. M. (1981) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/bfb0034536 · Cited by 334 · see citing works
Distribution of α1a-, α1b- and α1d-adrenergic receptor mRNA in the rat brain and spinal cord
Day, H. E. W., Campeau, S., Watson, S. J., & Akil, H. (1997) · Journal of Chemical Neuroanatomy · doi:10.1016/s0891-0618(97)00042-2 · Cited by 293 · see citing works
Sleep Neurobiology from a Clinical Perspective
España, R. A., & Scammell, T. E. (2011) · SLEEP · doi:10.5665/sleep.1112 · Cited by 282 · see citing works
Gilbey, M. P., Jordan, D., Richter, D. W., & Spyer, K. M. (1984) · The Journal of Physiology · doi:10.1113/jphysiol.1984.sp015453 · Cited by 261 · see citing works
Reflex discharge patterns of cardiac vagal efferent fibres
Kunze, D. L. (1972) · The Journal of Physiology · doi:10.1113/jphysiol.1972.sp009784 · Cited by 223 · see citing works
Standish, A., Enquist, L. W., Escardo, J., & Schwaber, J. S. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-03-01998.1995 · Cited by 180 · see citing works
Bcl-x Is Required for Proper Development of the Mouse Substantia Nigra
Savitt, J. M., Jang, S. S., Mu, W., Dawson, V. L., & Dawson, T. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0760-05.2005 · Cited by 173 · see citing works
Brain structures and receptors involved in alertness
Aston‐Jones, G. (2005) · Sleep Medicine · doi:10.1016/s1389-9457(05)80002-4 · Cited by 168 · see citing works
Neff, R. A., Wang, J., Baxi, S., Evans, C. R., & Mendelowitz, D. (2003) · Circulation Research · doi:10.1161/01.res.0000090361.45027.5b · Cited by 135 · see citing works
Self-citationSynaptic and Neurotransmitter Activation of Cardiac Vagal Neurons in the Nucleus Ambiguus
Wang, J.-J., Irnaten, M., Neff, R. A., Venkatesan, P., EVANS, C., Loewy, A. D., Mettenleiter, T. C., & Mendelowitz, D. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb03680.x · Cited by 134 · see citing works
Self-citationEvolution of β-blockers: from anti-anginal drugs to ligand-directed signalling
Baker, J. G., Hill, S. J., & Summers, R. J. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.02.010 · Cited by 134 · see citing works
Schneier, F. R. (2006) · New England Journal of Medicine · doi:10.1056/nejmcp060145 · Cited by 119 · see citing works
Morilak, D., Fornal, C., & Jacobs, B. (1987) · Brain Research · doi:10.1016/0006-8993(87)90536-1 · Cited by 104 · see citing works
Morilak, D. A., Fornal, C. A., & Jacobs, B. L. (1987) · Brain Research · doi:10.1016/0006-8993(87)90535-x · Cited by 102 · see citing works
Abbott, S. B. G., Kanbar, R., Bochorishvili, G., Coates, M. B., Stornetta, R. L., & Guyenet, P. G. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.232157 · Cited by 98 · see citing works
Firing properties of identified parasympathetic cardiac neurons in nucleus ambiguus
Mendelowitz, D. (1996) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1996.271.6.h2609 · Cited by 91 · see citing works
Self-citationDomain-restricted expression of two glutamic acid decarboxylase genes in midgestation mouse embryos
Katarova, Z., Sekerkov�, G., Prodan, S., Mugnaini, E., & Szab�, G. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20000904)424:4 · Cited by 91 · see citing works
Location, distribution and projections of intracardiac ganglion cells in the rat
Pardini, B. J., Patel, K. P., Schmid, P. G., & Lund, D. D. (1987) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(87)90106-8 · Cited by 90 · see citing works
Human heart rate variability and sleep stages
Toscani, L., Gangemi, P. F., Parigi, A., Silipo, R., Ragghianti, P., Sirabella, E., Morelli, M., Bagnoli, L., Vergassola, R., & Zaccara, G. (1996) · Neurological Sciences · doi:10.1007/bf01997720 · Cited by 83 · see citing works
Goldstein, M., Fuxé, K., Hökfelt, T. G. M., & Joh, T. H. (1971) · Cellular and Molecular Life Sciences · doi:10.1007/bf02135767 · Cited by 76 · see citing works
Identification and dissociation of cardiovascular neurons from the medulla for patch clamp analysis
Mendelowitz, D., & Kunze, D. L. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90305-d · Cited by 74 · see citing works
Self-citationPiñol, R. A., Bateman, R., & Mendelowitz, D. (2012) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2012.07.022 · Cited by 66 · see citing works
Self-citationMorilak, D., Fornal, C., & Jacobs, B. (1987) · Brain Research · doi:10.1016/0006-8993(87)90537-3 · Cited by 62 · see citing works
Gurtu, S., Pant, K. K., SINHA, J. N., & BHARGAVA, K. P. (1984) · Brain Research · doi:10.1016/0006-8993(84)90402-5 · Cited by 56 · see citing works
Role of the locus ceruleus in baroreceptor regulation of supraoptic vasopressin neurons in the rat
Grindstaff, R. J., Grindstaff, R. R., Sullivan, M. J., & Cunningham, J. T. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.1.r306 · Cited by 39 · see citing works
Frank, J. G., Jameson, H. S., Gorini, C., & Mendelowitz, D. (2009) · Journal of Neurophysiology · doi:10.1152/jn.91134.2008 · Cited by 38 · see citing works
Self-citationPhilbin, K. E., Bateman, R., & Mendelowitz, D. (2010) · Brain Research · doi:10.1016/j.brainres.2010.06.001 · Cited by 37 · see citing works
Self-citationNoradrenergic neurotransmission at PVN in locus ceruleus-induced baroreflex suppression in rats
Hwang, K.-R., Chan, S. H. H., & Chan, J. Y. H. (1998) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1998.274.4.h1284 · Cited by 34 · see citing works
Massari, V. J., Dickerson, L. W., Gray, A. L., Lauenstein, J., Blinder, K. J., Newsome, J. T., Rodak, D. J., Fleming, T. J., Gatti, P. J., & Gillis, R. A. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00613-1 · Cited by 33 · see citing works
Anxiolytics not acting at the benzodiazepine receptor: Beta blockers
Tyrer, P. J. (1992) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(92)90004-x · Cited by 32 · see citing works
Locus coeruleus involvement in the learning of classically conditioned bradycardia
Harris, G. C. M., & Fitzgerald, R. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-08-02314.1991 · Cited by 31 · see citing works
Primary vagally mediated decelerations in heart rate during tonic rapid eye movement sleep in cats
Verrier, R. L., Lau, T. R., Wallooppillai, U., Quattrochi, J. J., Nearing, B. D., Moreno, R., & Hobson, J. A. (1998) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1998.274.4.r1136 · Cited by 29 · see citing works
Bateman, R. J., Boychuk, C. R., Philbin, K. E., & Mendelowitz, D. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.02.033 · Cited by 28 · see citing works
Self-citationBoychuk, C. R., Bateman, R. J., Philbin, K. E., & Mendelowitz, D. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.024 · Cited by 25 · see citing works
Self-citationYao, S. T., Finkelstein, D. I., & Lawrence, A. J. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00661-7 · Cited by 22 · see citing works
Wake‐promoting actions of noradrenergic α1‐ and β‐receptors within the lateral hypothalamic area
Schmeichel, B. E., & Berridge, C. W. (2012) · European Journal of Neuroscience · doi:10.1111/ejn.12084 · Cited by 11 · see citing works
Effects of locus coeruleus lesions on heart rate during sleep in the cat.
Liesienė, V., Adrien, J., & Benoit, O. (1981) · PubMed · Cited by 3 · see citing works
Hagihara (1999) · doi:10.1002/(sici)1096-9861(19990726)410:2
Flagged first, then by citations
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Noradrenergic circuit control of non-REM sleep substates
Osorio-Forero, A., Cardis, R., Vantomme, G., Guillaume-Gentil, A., Katsioudi, G., Devenoges, C., Fernandez, L. M. J., & Lüthi, A. (2021) · Current Biology · doi:10.1016/j.cub.2021.09.041 · Cited by 230 · see citing works
Benarroch, E. E. (2017) · Cell and Tissue Research · doi:10.1007/s00441-017-2649-1 · Cited by 218 · see citing works
Parkinson disease and the gut: new insights into pathogenesis and clinical relevance
Travagli, R. A., Browning, K. N., & Camilleri, M. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0339-z · Cited by 181 · see citing works
Bellato, A., Arora, I., Hollis, C., & Groom, M. J. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.11.001 · Cited by 172 · see citing works
“SCL (which was averaged for each block as an index of SNS activity and a measure of BIS activation) increased as soon as rewards were extinguished in controls, but not in children with ADHD, indicating inefficient regulation of the ANS in response to a change in reinforcement contingencies (see results from HR measure…”
BackgroundInfluentialKunze, A., Summerskill, S. J., Marshall, R., & Filtness, A. J. (2019) · Ergonomics · doi:10.1080/00140139.2018.1547842 · Cited by 165 · see citing works
de Boer, S. F., Buwalda, B., & Koolhaas, J. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.07.008 · Cited by 163 · see citing works
Neurobiology of resilience in depression: immune and vascular insights from human and animal studies
Dudek, K., Dion‐Albert, L., Kaufmann, F. N., Tuck, E., Lebel, M., & Ménard, C. (2019) · European Journal of Neuroscience · doi:10.1111/ejn.14547 · Cited by 156 · see citing works
Faller, J., Cummings, J., Saproo, S., & Sajda, P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1817207116 · Cited by 131 · see citing works
Calcium imaging of sleep-wake related neuronal activity in the dorsal pons
Cox, J., Pinto, L., & Dan, Y. (2016) · Nature Communications · doi:10.1038/ncomms10763 · Cited by 133 · see citing works
Finnell, J. E., Lombard, C. M., Padi, A. R., Moffitt, C. M., Wilson, L. B., Wood, C. S., & Wood, S. K. (2017) · PLoS ONE · doi:10.1371/journal.pone.0172868 · Cited by 114 · see citing works
The brain norepinephrine system, stress and cardiovascular vulnerability
Wood, S. K., & Valentino, R. J. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.04.018 · Cited by 101 · see citing works
Habecker, B. A., Anderson, M. E., Birren, S. J., Fukuda, K., Herring, N., Hoover, D. B., Kanazawa, H., Paterson, D. J., & Ripplinger, C. M. (2016) · The Journal of Physiology · doi:10.1113/jp271840 · Cited by 101 · see citing works
How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses
Klumpers, F., Kroes, M. C. W., Baas, J. M. P., & Fernández, G. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3830-16.2017 · Cited by 95 · see citing works
Mather, M., Yoo, H. J., Clewett, D., Lee, T., Greening, S. G., Ponzio, A., Min, J., & Thayer, J. F. (2017) · NeuroImage · doi:10.1016/j.neuroimage.2017.02.025 · Cited by 77 · see citing works
Locus Coeruleus Shows a Spatial Pattern of Structural Disintegration in Parkinson's Disease
Madelung, C. F., Meder, D., Fuglsang, S. A., Marques, M. M., Boer, V. O., Madsen, K. H., Petersen, E. T., Hejl, A., Løkkegaard, A., & Siebner, H. R. (2022) · Movement Disorders · doi:10.1002/mds.28945 · Cited by 69 · see citing works
Wengrowski, A. M., Wang, X., Tapa, S., Posnack, N. G., Mendelowitz, D., & Kay, M. W. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu258 · Cited by 69 · see citing works
Self-citationFinnell, J. E., & Wood, S. K. (2016) · Neurobiology of Stress · doi:10.1016/j.ynstr.2016.04.001 · Cited by 68 · see citing works
Cardiac neuroanatomy - Imaging nerves to define functional control
Hanna, P., Rajendran, P. S., Ajijola, O. A., Vaseghi, M., Armour, J. A., Ardell, J. L., & Shivkumar, K. (2017) · Autonomic Neuroscience · doi:10.1016/j.autneu.2017.07.008 · Cited by 67 · see citing works
Asphyxia-activated corticocardiac signaling accelerates onset of cardiac arrest
Li, D., Mabrouk, O. S., Liu, T., Tian, F., Xu, G., Rengifo, S., Choi, S. J., Mathur, A., Crooks, C. P., Kennedy, R. T., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1423936112 · Cited by 59 · see citing works
Pharmacological evidence for the implication of noradrenaline in effort
Borderies, N., Mattioni, J., Bornert, P., Gilardeau, S., & Bouret, S. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000793 · Cited by 49 · see citing works
Wood, C. S., Valentino, R. J., & Wood, S. K. (2016) · Physiology & Behavior · doi:10.1016/j.physbeh.2016.07.008 · Cited by 45 · see citing works
Cauley, E. S., Wang, X., Dyavanapalli, J., Sun, K., Garrott, K. E., Kuzmiak‐Glancy, S., Kay, M. W., & Mendelowitz, D. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00445.2015 · Cited by 40 · see citing works
Self-citationMolecular and cellular neurocardiology in heart disease
Habecker, B. A., Bers, D. M., Birren, S. J., Chang, R. B., Herring, N., Kay, M. W., Li, D., Mendelowitz, D., Mongillo, M., Montgomery, J. M., et al. (2024) · The Journal of Physiology · doi:10.1113/jp284739 · Cited by 39 · see citing works
Self-citationQuinlan, M. A. L., Strong, V., Skinner, D. M., Martin, G. M., Harley, C. W., & Walling, S. G. (2019) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2018.00067 · Cited by 37 · see citing works
Optogenetics and pharmacogenetics: principles and applications.
Jiang, J., Cui, H.-X., & Rahmouni, K. (2017) · American Journal of Physiology. Regulatory Integrative and Comparative Physiology · doi:10.1152/ajpregu.00091.2017 · Cited by 30 · see citing works
Arousal dysregulation and executive dysfunction in attention deficit hyperactivity disorder (ADHD)
Isaac, V., López, V., & Escobar, M. J. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1336040 · Cited by 34 · see citing works
Parasympathetic Vagal Control of Cardiac Function
Dyavanapalli, J., Dergacheva, O., Wang, X., & Mendelowitz, D. (2016) · Current Hypertension Reports · doi:10.1007/s11906-016-0630-0 · Cited by 32 · see citing works
Self-citationIdrees, I., Bellato, A., Cortese, S., & Groom, M. J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104968 · Cited by 34 · see citing works
Heightened interoception in adults with fibromyalgia
Todd, J., Plans, D., Lee, M., Bird, J. M., Morelli, D., Cunningham, A. C., Ponzo, S., Murphy, J., Bird, G., & Aspell, J. E. (2024) · Biological Psychology · doi:10.1016/j.biopsycho.2024.108761 · Cited by 32 · see citing works
Sharp, D., Wang, X., & Mendelowitz, D. (2014) · Brain Research · doi:10.1016/j.brainres.2014.06.010 · Cited by 31 · see citing works
Self-citationCardiac optogenetics: a novel approach to cardiovascular disease therapy
Jiang, C., Li, H. T., Zhou, Y. M., Wang, X., Wang, L., & Liu, Z. Q. (2017) · EP Europace · doi:10.1093/europace/eux345 · Cited by 31 · see citing works
Self-citationNovel approaches to restore parasympathetic activity to the heart in cardiorespiratory diseases
Dyavanapalli, J. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00398.2020 · Cited by 27 · see citing works
Direct projections from hypothalamic orexin neurons to brainstem cardiac vagal neurons
Dergacheva, O., Yamanaka, A., Schwartz, A. R., Polotsky, V. Y., & Mendelowitz, D. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.09.038 · Cited by 28 · see citing works
Self-citationHoffmeister, J. D., Kelm‐Nelson, C. A., & Ciucci, M. R. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113514 · Cited by 28 · see citing works
Error-related cardiac response as information for visibility judgements
Łukowska, M., Sznajder, M., & Wierzchoń, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-19144-0 · Cited by 26 · see citing works
Neuro-physiological correlates of sluggish cognitive tempo (SCT) symptoms in school-aged children
Yung, T. W. K., Lai, C. Y. Y., Chan, J. Y. C., Ng, S. S. M., & Chan, C. C. H. (2020) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-019-01353-1 · Cited by 23 · see citing works
Kaźmierczak, M., & Nicola, S. M. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.07.008 · Cited by 24 · see citing works
Zhang, J., Luo, H., Pace, E., Li, L., & Liu, B. (2015) · Hearing Research · doi:10.1016/j.heares.2015.08.006 · Cited by 22 · see citing works
Regulation of Cardiac Function by the Autonomic Nervous System
Hafez, O. A., & Chang, R. B. (2024) · Physiology · doi:10.1152/physiol.00018.2024 · Cited by 22 · see citing works
Targeting Parasympathetic Activity to Improve Autonomic Tone and Clinical Outcomes
Kay, M. W., Jain, V., Panjrath, G. S., & Mendelowitz, D. (2021) · Physiology · doi:10.1152/physiol.00023.2021 · Cited by 20 · see citing works
Self-citationJohn, A., Barthel, A., Wind, J., Rizzi, N., & Schöllhorn, W. I. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.816334 · Cited by 19 · see citing works
Accurate nonrigid 3D human body surface reconstruction using commodity depth sensors
Lu, Y., Shang, Z., Younes, N., & Hahn, J. (2018) · Comput. Animat. Virtual Worlds · doi:10.1002/cav.1807 · Cited by 21 · see citing works
Sex-steroid-dependent plasticity of brain-stem autonomic circuits
Littlejohn, E. L., Fedorchak, S., & Boychuk, C. R. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00357.2019 · Cited by 18 · see citing works
The state of the art of biomedical applications of optogenetics
Neghab, H. K., Soheilifar, M. H., Grusch, M., Ortega, M. M., Djavid, G. E., Saboury, A. A., & Goliaei, B. (2021) · Lasers in Surgery and Medicine · doi:10.1002/lsm.23463 · Cited by 18 · see citing works
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Bierwirth, P., & Stockhorst, U. (2022) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2022.107660 · Cited by 19 · see citing works
Pate, B. S., Bouknight, S. J., Harrington, E. N., Mott, S., Augenblick, L. M., Smiley, C. E., Morgan, C. G., Calatayud, B. M., Martínez-Muñiz, G. A., Thayer, J. F., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.01.011 · Cited by 17 · see citing works
Diverse ancestral brainstem noradrenergic neuron activity across species and biological factorsPreprint
Kelberman, M. A., Rodberg, E. M., Munn, B. R., Arabzadeh, E., Bair-Marshall, C. J., Berridge, C. W., Berrocoso, E., Breton‐Provencher, V., Chandler, D. J., Che, A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.14.618224 · Cited by 19 · see citing works
Broadfoot, C. K., Lenell, C., Kelm‐Nelson, C. A., & Ciucci, M. R. (2022) · SSRN Electronic Journal · doi:10.1016/j.bbr.2022.114157 · Cited by 15 · see citing works
Cardiac autonomic activity during sleep deprivation with and without caffeine administration
Crooks, E., Hansen, D., Satterfield, B. C., Layton, M. E., & Dongen, H. P. A. V. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112643 · Cited by 19 · see citing works
Leikauf, J. E., Griffiths, K. R., Saggar, M., Hong, D. S., Clarke, S., Efron, D., Tsang, T. W., Hermens, D. F., Kohn, M. R., & Williams, L. M. (2017) · Personalized Medicine in Psychiatry · doi:10.1016/j.pmip.2017.02.001 · Cited by 14 · see citing works
Synthetic biology of cell signaling
Hansen, J., & Benenson, Y. (2015) · Natural Computing · doi:10.1007/s11047-015-9526-1 · Cited by 13 · see citing works
An optogenetic mouse model of rett syndrome targeting on catecholaminergic neurons
Zhang, S., Johnson, C. M., Cui, N., Xing, H., Zhong, W., Wu, Y., & Jiang, C. L. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23760 · Cited by 11 · see citing works
Autonomic Nervous System Functioning in ADHD
Bellato, A., Wiersema, J. R., & Groom, M. J. (2023) · Autism and child psychopathology series · doi:10.1007/978-3-031-41709-2_3 · Cited by 11 · see citing works
Advancing organ-on-chip systems: the role of microfluidics in neuro-cardiac research
Ferreira, M. J., Colombani, S., Bernardin, A. A., Lacampagne, A., Pasquié, J., Costa, P. F., Charlot, B., & Méli, A. C. (2025) · Current Research in Pharmacology and Drug Discovery · doi:10.1016/j.crphar.2025.100227 · Cited by 9 · see citing works
Optogenetic Control of Cardiac Autonomic Neurons in Transgenic Mice
Moreno, A., Kowalik, G., Mendelowitz, D., & Kay, M. W. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0830-2_18 · Cited by 9 · see citing works
Self-citationAutonomic Nervous System and Neurocardiac Physiopathology
Kingma, J. G., Simard, D., & Rouleau, J. R. (2018) · InTech eBooks · doi:10.5772/intechopen.77087 · Cited by 7 · see citing works
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Hasan, S., Delicata, F., Guasti, L., Duranti, C., Haidar, F. M., Arcangeli, A., Imbrici, P., Pessia, M., Valentino, M., & D’Adamo, M. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315334 · Cited by 6 · see citing works
Next-Generation Tools to Study Autonomic Regulation In Vivo
Mukerjee, S., & Lazartigues, E. D. (2018) · Neuroscience Bulletin · doi:10.1007/s12264-018-0319-2 · Cited by 6 · see citing works
Aiba, I., & Noebels, J. L. (2019) · Journal of Neurophysiology · doi:10.1152/jn.00761.2018 · Cited by 6 · see citing works
The impact of dog therapy on nursing students’ heart rates and ability to pay attention in class
Griscti, O., & Camilleri, L. (2019) · International Journal of Educational Research · doi:10.1016/j.ijer.2019.101498 · Cited by 6 · see citing works
Central Nervous System Management of Autonomic Cardiovascular Control
Ruffinazzi, M., & Dusi, V. (2021) · Springer eBooks · doi:10.1007/978-3-319-90305-7_65-1 · Cited by 6 · see citing works
Dundon, N. M., Stuber, A., Bullock, T., Garcia, J. O., Babenko, V., Rizor, E. J., Yang, D., Giesbrecht, B., & Grafton, S. T. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.2008-23.2024 · Cited by 4 · see citing works
Beach, P. A., Hyland, S., Chen, X., & Huddleston, D. E. (2025) · Clinical Autonomic Research · doi:10.1007/s10286-025-01164-2 · Cited by 3 · see citing works
Yung, T. W. K., Lai, C. Y. Y., & Chan, C. C. H. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.875064 · Cited by 3 · see citing works
Blunted response of caudal locus coeruleus to arousing stimuli in Parkinson’s disease
Lund, A. E., Madelung, C. F., Madsen, K. H., Thomsen, B. L. C., Løkkegaard, A., Meder, D., & Siebner, H. R. (2026) · Brain · doi:10.1093/brain/awag106 · Cited by 2 · see citing works
Sensory Modulation: a Window to Sluggish Cognitive Tempo Symptoms Among Children
Yung, T. W. K. (2021) · Current Developmental Disorders Reports · doi:10.1007/s40474-021-00238-w · Cited by 2 · see citing works
Engborg, C. B., Pujar, M., Kanadia, R., & Sciolino, N. R. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.08.046 · Cited by 2 · see citing works
Russo, R., Moreno, A., Dwyer, M. K. R., Skancke, M., Trachiotis, G., Mendelowitz, D., & Kay, M. W. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00418.2025 · Cited by 2 · see citing works
Self-citationA6 neurons simultaneously modulate active expiration and upper airway resistance in rats
Magalhães, K. S., de Britto, A. A., Paton, J. F. R., & Moraes, D. J. A. (2019) · Experimental Physiology · doi:10.1113/ep088164 · Cited by 2 · see citing works
Jacobsen, S. S., Morehouse, A. B., Chen, P., Gomolka, R. S., Andersen, M. M., Nedergaard, M., Mednick, S. C., & Kjærby, C. (2026) · eLife · doi:10.7554/elife.110252.1 · Cited by 2 · see citing works
Wang, Y. B., Saunders, S. E., Campbell, J. N., & Boychuk, C. R. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103068 · Cited by 1 · see citing works
Jacobsen, S. M., Morehouse, A. B., Chen, P., Qian, Y., Gomolka, R. S., Andersen, M., Nedergaard, M., Mednick, S. C., & Kjærby, C. (2026) · eLife · doi:10.7554/elife.110252.3 · Cited by 1 · see citing works
Zhang, S. (2022) · Digital Archive @ GSU · doi:10.57709/8486904 · Cited by 1 · see citing works
A5 and A6 Noradrenergic Cell Groups: Implications for Cardiorespiratory Control
López-González, M. V., González-García, M., & Dawid-Milner, M. S. (2018) · InTech eBooks · doi:10.5772/intechopen.79389 · Cited by 1 · see citing works
Hancheva, O. V., Данукало, М. В., & Melnikova, О. V. (2019) · Pathologia · doi:10.14739/2310-1237.2019.1.166145 · Cited by 1 · see citing works
Impact of Music on Cardiac Patients
Mastnak, W. (2015) · Musik- Tanz- und Kunsttherapie · doi:10.1026/0933-6885/a000222
Aiba, I., & Noebels, J. L. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/276998
Bloemraad, R., Boekenoogen, N., van den Broek, J. M., Palmen, M., Wallner, G., & Bernhaupt, R. (2020) · Annual Symposium on Computer-Human Interaction in Play · doi:10.1145/3383668.3419866
A Photoactivatable Norepinephrine for Probing Adrenergic Neural CircuitsPreprint
Cahill, M. K., Pérez, Y. R., Larpthaveesarp, A., Etchenique, R., & Poskanzer, K. E. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.13.566764
(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.09996-8
Feedback Enhances Training and Elicits Biometric Responses in Novel Flexible Nasolaryngoscopy Model
Fernández‐Penny, F. E., Clements, A. C., Meyer, T. K., Le, H., Bindschadler, M., Friedman, S. D., & Sardesaı, M. G. (2025) · The Laryngoscope · doi:10.1002/lary.32231
Jian, S., Zhang, Z., Yue, L., Jia, T., & Yufeng, Y. (2025) · Lecture notes in computer science · doi:10.1007/978-3-031-92689-1_6
Flockton, J. R., McCall, C., & Preston, C. (2025) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2025.1688172
Brainstem origin of Parkinson's disease symptoms
Tissone, A. I., & Esposito, M. S. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-21992-4.00011-7
Yüksel, Ç., McCoy, E., Watford, L., Muranaka, M., Sen, M., Lax, H., Bobowski, L., Daffre, C., Bostian, C. M., Oliver, K. I., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.02.703359
Jacobsen, S. S., Morehouse, A. B., Chen, P., Qian, Y., Gomolka, R. S., Andersen, M., Nedergaard, M., Mednick, S. C., & Kjærby, C. (2026) · eLife · doi:10.7554/elife.110252
Metabolism-Mediated Regulation of Brain–Heart Interactions
Liu, Z., Peng, R., & Zhao, L. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27093712
Jacobsen, S. S., Morehouse, A. B., Chen, P., Qian, Y., Gomolka, R. S., Andersen, M., Nedergaard, M., Mednick, S. C., & Kjærby, C. (2026) · eLife · doi:10.7554/elife.110252.2
- Authors
- Wang, X., Piñol, R. A., Byrne, P., & Mendelowitz, D.
- Affiliations
- George Washington University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-04-30
- Volume
- 34
- Issue
- 18
- Pages
- 6182-6189
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4004807
- OpenAlex
- W2026113561
- Cited by
- 89
- References
- 52
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 7 · 2023: 2 · 2022: 11 · 2021: 6 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 8 · 2016: 9 · 2015: 5 · 2014: 2
- FWCI
- 5.50
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HL 59895, HL49965)
- National Heart, Lung, and Blood Institute (HL 49965, R01HL072006, HL72006, R01HL049965, R01HL059895, HL59895)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- locus coeruleus, noradrenergic neurons, inhibitory neurotransmission, alpha1-adrenoceptors, beta1-adrenergic receptor, autonomic regulation of heart rate, tachycardia
- MeSH terms
- Channelrhodopsins, Afferent Pathways, Animals, Bacterial Proteins, Brain Stem, Glycine, Heart, Locus Coeruleus, Luminescent Proteins, Mice, Transgenic, Neurons, Photic Stimulation, Tyrosine 3-Monooxygenase, Vagus Nerve, Receptors, Adrenergic, alpha-1, Receptors, Adrenergic, beta-1, Patch-Clamp Techniques, Adrenergic Agents, Mice, Inhibitory Postsynaptic Potentials, Optogenetics
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