Meaghan Creed

Meaghan Creed is a Canadian Neuroscientist and Assistant Professor of Anesthesiology at Washington University in St. Louis, Missouri. Creed has conducted research on understanding and optimizing deep brain stimulation in the basal ganglia for the treatment of neurological and psychiatric disorders. Her work has been recognized at the national and international level by Pfizer, the American Association for the Advancement of Science (AAAS), and the Rita Allen Foundation.

Meaghan Creed
Born
Chatham, ON, Canada
NationalityCanadian
Alma materB.S. and Ph.D. University of Toronto, Postdoctoral Work at University of Geneva
Known forUsing Deep Brain Stimulation (DBS) to modulate neural circuitry
Awards2019 Rita Allen Foundation Scholar Award in Pain, NARSAD Young Investigator Grant, Brain and Behavior Research Foundation, American College of Neuropsychopharmacology, 2017 Science AAAS-PINS Inaugural Prize In Neuromodulation, 2016 Prix Pfizer de le Recherche / Pfizer Research Prize for Outstanding Translational
Scientific career
FieldsNeuroscience
InstitutionsWashington University in St. Louis

Early life and education

Creed grew up in Chatham, Ontario, Canada, on the banks of Lake St. Clair.[1][2] She attended McNaughton Avenue Public School and became interested in biology as early as grade 2 when a scientist came into her classroom to talk about genetically engineered corn.[1] She then moved on to complete high school at Chatham-Kent Secondary School where she had further mentorship and guidance towards a path in science.[1] Creed says that her physics, biology, and chemistry teachers were formative in motivating her to pursue biology in her undergraduate degree.[1] Creed moved towards the Greater Toronto Area in 2004 to conduct her undergraduate research at the University of Toronto at the Scarborough Campus.[1] She graduated in 2008 with an Honours Bachelor of Science.[3] Creed stayed with the University of Toronto for her graduate studies, but moved into the heart of downtown to conduct her research at the Center for Addiction and Mental Health under the mentorship of Jose N. Nobrega.[3] Her graduate studies focused on exploring the use of deep brain stimulation (DBS) in treating movement disorders.[3] Creed completed her PhD in pharmacology and neuroscience in 2012.[1]

Pursuing further experience in neuroscience, Creed moved to Switzerland to complete her postdoctoral work at the University of Geneva in the Department of Basic Neuroscience.[4] She worked under the mentorship of Christian Lüscher where she learned how to use techniques such as optogenetics and electrophysiology in models of cocaine addiction.[5] In her postdoctoral work, she used her knowledge and expertise in DBS to see how it could be leveraged to reduce synaptic plasticity in the mesolimbic reward circuitry in response to cocaine addiction.[2]

Deep brain stimulation

Early into Creed’s PhD, she explored the neural substrates driving tardive dyskinesia (TD), a late-onset side effect of taking long-term antipsychotics, and found that structural synaptic alterations are probably not the underlying cause of the disorder.[6] These findings suggested alternative functional neuroplastic changes as a cause of TD, so Creed decided to explore the possibility of alleviating TD with deep brain stimulation (DBS).[7] Strikingly, Creed found that DBS at 130 Hz applied specifically to the entopeduncular nucleus (EPN) or the subthalamic nucleus (STN) was effective at reducing symptoms of TD in a mouse model.[7] Her findings showed that DBS might provide therapeutic relief to patients suffering from drug-induced dyskinesias.[7] In her thesis work, Creed further showed that the changes caused by DBS are not the same as pharmacological inactivation, that DBS in the STN decreases serotonin output of dorsal raphe neurons, and that modulation of dopamine release is not related to the anti-dyskinetic effects of DBS.[8] Creeds explorations of how DBS impacts neural activity and neural circuitry established some of the first findings into the mechanisms of DBS as well as providing a model with which to further study them.[8]

After defending her thesis, Creed published several more papers highlighting her graduate DBS findings. Creed highlighted the immediate early genetic changes that result from DBS treatment and found that DBS stimulation of the EPN caused increases in immediate early gene mRNA, a marker of increased activity, in the basal ganglia, but decreases in the thalamus and motor cortex, while stimulation to the STN decreased immediate early gene mRNA levels in all basal ganglia structures, the thalamus, and the motor cortex.[9] These results suggest that divergent neuroanatomic mechanisms in the EPN and STN, upon DBS stimulation, lead to similar behavioral outcomes.[9]

In her postdoctoral work, Creed studied DBS in the context of drug addiction in the Lüscher Lab at the University of Geneva. In the context of cocaine addiction, drug-adaptive behavior is driven by remodelling of the brain’s reward circuitry, specifically plasticity of the excitatory inputs onto dopaminergic ventral tegmental area neurons.[10] Creed and her colleagues found that cocaine administration leads to long-lasting increases in burst firing due to impaired function of calcium activated small conductance potassium channels (SK channels).[10] Creed found that cocaine exposure drove insertion of GluN3A-containing NMDAR onto VTA dopamine neurons which impaired their excitability and prevented the activation of the SK channels.[10]

After exploring the synaptic level changes that occur in dopamine neurons in addiction models, Creed was ready to test if DBS could help to reverse these plasticity changes and relieve symptoms of addiction.[11] In a first author paper in Science, Creed reported that acute low frequency stimulation via DBS can mimic previous findings with optogenetics in which stimulation reverses the synaptic changes that led to addiction.[11] This finding was one of the first to show that DBS can be used like optogenetics to cause synaptic level and behavioral changes in mice, a finding that increases the translational potential of optogenetic studies.[11]

Career and Research

After her postdoctoral work in Switzerland, Creed came back to North America in 2016 as she was recruited to be an Assistant Professor of Pharmacology at the University of Maryland School of Medicine.[12] Creed’s lab at the University of Maryland focused on probing the neural circuitry underlying reward-seeking, risk tolerance, impulsivity, and anhedonia in order to one day develop strategies to modulate these circuits in a therapeutic manner.[4]

Creed was recruited to Washington University in St. Louis in October 2018, where she now holds the title of Assistant Professor of Anesthesiology and runs her lab in the Pain Center within the department of Psychiatry.[3] Creed’s lab focuses on developing novel neuromodulatory approaches to treat brain related disorders such as depression, chronic pain, and addiction.[13] The types of neuromodulatory therapies her lab focuses on are deep brain stimulation, targeted drug delivery, and neurostimulation with focused ultrasound.[13]

The first paper published by the Creed Lab in 2018 explored the distinct population of Glutamatergic ventral pallidum (VP) neurons and their role in reward seeking behavior.[14] Creed and her team found that VP neurons have excitatory projections to lateral habenula, rostromedial tegmental nucleus, and GABAergic VTA neurons.[14] They also found that selective activation of this subpopulation of VP glutamatergic neurons induced place avoidance suggesting their role in constraining reward seeking behavior.[14] Continuing to explore the VP, Creed and her team looked at the role of the GABAergic VP neurons in appetitive and aversive behavior.[15] They first explored human imaging studied to look at the role of the VP in the human brain and found that it tracks reward-sensitivity and motivation to seek rewards.[15] They further found that a subsection of the VP seemed to be implicated in processing aversive information.[15] They mimicked these findings in the rodent brain using in vivo electrophysiology and behavioral pharmacology which poses the question as to how the mechanisms by which the VP is able to elicit such distinct behavioral outputs, aversive or appetitive behaviors, when it plays a role in both.[15] Their findings set up the anatomical and molecular background for future studies to probe these questions.

Her lab also is a proponent of Open Science. In 2018, they developed an Open Source lickometer, that allows scientists to easily detect when mice lick for specific substances in self administration and sucrose preference tasks.[16] They made the instructions, the code and the schematics all open source.[16] Further, in 2019, they received funding from the McDonnell Center for Systems Neuroscience at Washington University, in addition to donations from the WashU Pain Center and Anesthesiology Division of Basic Research to support a series of workshops to introduce people to open source techniques like DeepLabCut, co developed by Mackenzie Mathis and Alexander Mathis, Bonsai, and Arduino.[17]

Awards and honors
  • 2019 Rita Allen Foundation Scholar Award in Pain[18]
  • NARSAD Young Investigator Grant, Brain and Behavior Research Foundation - Cellular adaptations underlying learned helplessness behavior[3]
  • 2017 Science AAAS-PINS Inaugural Prize In Neuromodulation[4]
  • 2016 Prix Pfizer de le Recherch / Pfizer Research Prize for Outstanding Translational Research[19]

Select publications
  • Fobbs WC, Bariselli S, Licholai JA, Miyazaki NL, Matikainen-Ankney BA, Creed MC, Kravitz AV. Continuous representations of speed by striatal medium spiny neurons. J Neurosci. 2020 Feb 19;40(8):1679-1688.[20]
  • Godynyuk E, Bluitt MN, Tooley JR, Kravitz AV, Creed MC. An open-source, automated, home-cage sipper device for monitoring liquid ingestive behavior in rodents. eNeuro. 2019. 10;6(5).[21]
  • Tooley J, Marconi L, Alipio JB, Matikainen-Ankney B, Georgiou P, Kravitz AV, Creed M. Glutamatergic ventral pallidal neurons modulate activity of the habenula - tegmental circuitry and constrain reward seeking. Biological Psychiatry.  2018.[14]
  • Creed MC. Current and emerging neuromodulation therapies for addiction: insight from pre-clinical studies.Current Opinion in Neurobiology.  2018.[22]
  • Creed M, Pascoli VP, Lüscher C. Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology. Science. 2015. 347(6222):659-64.
  • Creed M, Ntamati R, Chandra R, Lobo MK, Lüshcer C.  Convergence of rewarding and anhedonic effects of cocaine in the ventral pallidum. Neuron. 2016.  92(1): 214-226.[11]
  • Lee D*, Creed M*, Jung K*, Wendler DJ, Oh WC, Mignocchi NL, Lüscher C, and Kwon HB. Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain. Nature Methods.  2017.  14(5):495-503.[23]
  • Creed MC, Hamani C, Nobrega JN. Effects of repeated deep brain stimulation on depressive- and anxiety-like behavior in rats: comparing entopeduncular and subthalamic nuclei. Brain Stimulation. 2012. 6(4):506-14.[24]
  • Creed MC, Hamani C, Bridgeman A, Fletcher PJ, Nobrega JN. Contribution of decreased serotonin release to the antidyskinetic effects of deep brain stimulation in a rodent model of tardive dyskinesia: comparison of the subthalamic and entopeduncular nuclei. Journal of Neuroscience.  2012. 32(28)9874-81.[25]
  • Creed MC, Hamani C, Nobrega JN. Early gene mapping after deep brain stimulation in a rat model of tardive dyskinesia: comparison with transient local inactivation.  European Journal of Neuropsychopharmacology. 2011. 22(7):506-517.[26]

References
  1. "Creed rewarded for her neuro research". The Chatham Voice. 2017-09-13. Retrieved 2020-04-17.
  2. "People". Creed Lab. Retrieved 2020-04-17.
  3. "Meaghan Creed". Creed Lab. Retrieved 2020-04-17.
  4. "Meaghan Creed Awarded Science & PINS Prize for Neuromodulation". American Association for the Advancement of Science. Retrieved 2020-04-17.
  5. "Meaghan Creed - C. Lüscher Synapses, circuits and behaviour in addiction and related disorders - UNIGE". www.addictionscience.unige.ch. 2012-09-19. Retrieved 2020-04-17.
  6. "APA PsycNet". psycnet.apa.org. Retrieved 2020-04-17.
  7. Creed, Meaghan; Hamani, Clement; Nobrega, José N. (2011-05-01). "Deep brain stimulation of the subthalamic or entopeduncular nucleus attenuates vacuous chewing movements in a rodent model of tardive dyskinesia". European Neuropsychopharmacology. 21 (5): 393–400. doi:10.1016/j.euroneuro.2010.06.012. ISSN 0924-977X. PMID 20624675.
  8. Creed, Meaghan Claire (2013-12-12). Deep Brain Stimulation of the Subthalamic and Entopeduncular Nuclei in an Animal Model of Tardive Dyskinesia (Thesis thesis).
  9. Creed, Meaghan C.; Hamani, Clement; Nobrega, José N. (2012-07-01). "Early gene mapping after deep brain stimulation in a rat model of tardive dyskinesia: Comparison with transient local inactivation". European Neuropsychopharmacology. 22 (7): 506–517. doi:10.1016/j.euroneuro.2011.11.004. ISSN 0924-977X. PMID 22153973.
  10. Creed, Meaghan; Kaufling, Jennifer; Fois, Giulia R.; Jalabert, Marion; Yuan, Tifei; Lüscher, Christian; Georges, Francois; Bellone, Camilla (2016-10-19). "Cocaine Exposure Enhances the Activity of Ventral Tegmental Area Dopamine Neurons via Calcium-Impermeable NMDARs". Journal of Neuroscience. 36 (42): 10759–10768. doi:10.1523/JNEUROSCI.1703-16.2016. ISSN 0270-6474. PMC 6601891. PMID 27798131.
  11. Creed, Meaghan; Pascoli, Vincent Jean; Lüscher, Christian (2015-02-06). "Refining deep brain stimulation to emulate optogenetic treatment of synaptic pathology". Science. 347 (6222): 659–664. doi:10.1126/science.1260776. ISSN 0036-8075. PMID 25657248.
  12. "Meaghan C. Creed, PhD". Neuromodulation: The Science Conference. Retrieved 2020-04-17.
  13. "Meaghan Creed, PhD". The Hope Center. Retrieved 2020-04-17.
  14. Tooley, Jessica; Marconi, Lauren; Alipio, Jason Bondoc; Matikainen-Ankney, Bridget; Georgiou, Polymnia; Kravitz, Alexxai V.; Creed, Meaghan C. (2018-06-15). "Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula–Tegmental Circuitry and Constrain Reward Seeking". Biological Psychiatry. Impulsivity: Mechanisms and Manifestations. 83 (12): 1012–1023. doi:10.1016/j.biopsych.2018.01.003. ISSN 0006-3223. PMC 5972062. PMID 29452828.
  15. Wulff, Andreas B.; Tooley, Jessica; Marconi, Lauren J.; Creed, Meaghan C. (2019-06-15). "Ventral pallidal modulation of aversion processing". Brain Research. More than a reward molecule: The role of dopamine in aversively motivated behavior. 1713: 62–69. doi:10.1016/j.brainres.2018.10.010. ISSN 0006-8993. PMID 30300634.
  16. "Automated mouse homecage two-bottle choice test v2". hackaday.io. Retrieved 2020-04-17.
  17. "News". Creed Lab. Retrieved 2020-04-17.
  18. "Creed, McCall named Rita Allen Foundation Scholars". Washington University School of Medicine in St. Louis. 2019-07-10. Retrieved 2020-04-17.
  19. "Pfizer Award 2016 to Meaghan Creed & Vincent Pascoli | NCCR-Synapsy". Retrieved 2020-04-17.
  20. Fobbs, Wambura C.; Bariselli, Sebastiano; Licholai, Julia A.; Miyazaki, Nanami L.; Matikainen-Ankney, Bridget A.; Creed, Meaghan C.; Kravitz, Alexxai V. (2020-02-19). "Continuous Representations of Speed by Striatal Medium Spiny Neurons". Journal of Neuroscience. 40 (8): 1679–1688. doi:10.1523/JNEUROSCI.1407-19.2020. ISSN 0270-6474. PMC 7046334. PMID 31953369.
  21. Godynyuk, Elizabeth; Bluitt, Maya N.; Tooley, Jessica R.; Kravitz, Alexxai V.; Creed, Meaghan C. (2019-09-01). "An Open-Source, Automated Home-Cage Sipper Device for Monitoring Liquid Ingestive Behavior in Rodents". eNeuro. 6 (5): ENEURO.0292–19.2019. doi:10.1523/ENEURO.0292-19.2019. ISSN 2373-2822. PMC 6787345. PMID 31533961.
  22. Creed, Meaghan (April 2018). "Current and emerging neuromodulation therapies for addiction: insight from pre-clinical studies". Current Opinion in Neurobiology. 49: 168–174. doi:10.1016/j.conb.2018.02.015. ISSN 1873-6882. PMID 29524847.
  23. Lee, Dongmin; Creed, Meaghan; Jung, Kanghoon; Stefanelli, Thomas; Wendler, Daniel J.; Oh, Won Chan; Mignocchi, Neymi Layne; Lüscher, Christian; Kwon, Hyung-Bae (May 2017). "Temporally precise labeling and control of neuromodulatory circuits in the mammalian brain". Nature Methods. 14 (5): 495–503. doi:10.1038/nmeth.4234. ISSN 1548-7105. PMID 28369042.
  24. Creed, Meaghan C.; Hamani, Clement; Nobrega, José N. (July 2013). "Effects of repeated deep brain stimulation on depressive- and anxiety-like behavior in rats: comparing entopeduncular and subthalamic nuclei". Brain Stimulation. 6 (4): 506–514. doi:10.1016/j.brs.2012.09.012. ISSN 1876-4754. PMID 23088853.
  25. Creed, Meaghan C.; Hamani, Clement; Bridgman, Alanna; Fletcher, Paul J.; Nobrega, José N. (2012-07-11). "Contribution of decreased serotonin release to the antidyskinetic effects of deep brain stimulation in a rodent model of tardive dyskinesia: comparison of the subthalamic and entopeduncular nuclei". The Journal of Neuroscience. 32 (28): 9574–9581. doi:10.1523/JNEUROSCI.1196-12.2012. ISSN 1529-2401. PMC 6622267. PMID 22787043.
  26. Creed, Meaghan C.; Hamani, Clement; Nobrega, José N. (July 2012). "Early gene mapping after deep brain stimulation in a rat model of tardive dyskinesia: comparison with transient local inactivation". European Neuropsychopharmacology. 22 (7): 506–517. doi:10.1016/j.euroneuro.2011.11.004. ISSN 1873-7862. PMID 22153973.
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