This is an application for an administrative diversity supplement to R37 NS046579-16, ?Action and interaction of ionotropic and metabotropic neurotransmission? to support the scientific training and development of Rochinelle Dongmo. Ms. Dongmo is a baccalaureate degree holder from Emory University who is currently enrolled in a post-baccalaureate research scholars program at Harvard to prepare for Ph.D. graduate programs in neuroscience, with the goal of enrolling in a program by the Fall of 2021. As a black woman who is a U.S. permanent resident currently finishing her naturalization as an American citizen from Cameroon, she is part of an ethnic group underrepresented in biomedical research. Ms. Dongmo's research in the lab will pursue two aims related to the parent grant, both of them seeking to better understand the mechanism of metabotropic neurotransmission to non-neuronal microglia. In the first aim, Ms. Dongmo will develop an imaging assay to assess microglia activation in ex vivo brain slices via changes in gross morphology. This assay will allow us to test the activation of microglia to multiple neurotransmitters, most notably acetylcholine and GABA, for which microglia are known to possess metabotropic receptors. In the second aim, Ms. Dongmo will measure the effects of microglia activation on the intracellular activity of Ca2+ and protein kinase A (PKA), two central intracellular signaling molecules. She will test the Ca2+ and PKA activity in response to both known activators of microglia, as well as to GABA and acetylcholine, whose net effect on microglia activation will be determined in her first aim. She will be mentored during the execution of this research plan on both all scientific and technical aspects of the research. We have designed a comprehensive mentorship and training plan for Ms. Dongmo including lab experience, regular one-on-one meetings with the PI and a senior post-doc, conference presentations, all in addition to her participation in the Harvard Research Scholars Initiative, which includes classes, workshops, tutoring, GRE test preparation, and graduate school application guidance. These research and career development plans will prepare Ms. Dongmo for a successful academic career in research neuroscience.

Public Health Relevance

Non-neuronal cells such as microglia are known to express receptors for classical neurotransmitters such as acetylcholine and GABA, but the effect of neurotransmission on the activity of microglia remains unknown. This supplement will support Ms. Rochinelle Dongmo to establish assays that study the activation and intracellular signaling of microglia in response to neurotransmitters classically thought to only effect other neurons. These results will establish new methods to probe the biology of microglia, which are central mediators of proper neuronal function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37NS046579-16S1
Application #
10166240
Study Section
Program Officer
Churn, Severn Borden
Project Start
2020-09-01
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
16
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Zhang, Peng; Lu, Hong; Peixoto, Rui T et al. (2018) Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships. Cell 174:1450-1464.e23
Hrvatin, Sinisa; Hochbaum, Daniel R; Nagy, M Aurel et al. (2018) Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex. Nat Neurosci 21:120-129
Chen, Yao; Granger, Adam J; Tran, Trinh et al. (2017) Endogenous G?q-Coupled Neuromodulator Receptors Activate Protein Kinase A. Neuron 96:1070-1083.e5
Wallace, Michael L; Saunders, Arpiar; Huang, Kee Wui et al. (2017) Genetically Distinct Parallel Pathways in the Entopeduncular Nucleus for Limbic and Sensorimotor Output of the Basal Ganglia. Neuron 94:138-152.e5
Gross, Garrett G; Junge, Jason A; Mora, Rudy J et al. (2013) Recombinant probes for visualizing endogenous synaptic proteins in living neurons. Neuron 78:971-85
Olson, Jeremy P; Kwon, Hyung-Bae; Takasaki, Kevin T et al. (2013) Optically selective two-photon uncaging of glutamate at 900 nm. J Am Chem Soc 135:5954-7
Ding, Jun B; Oh, Won-Jong; Sabatini, Bernardo L et al. (2011) Semaphorin 3E-Plexin-D1 signaling controls pathway-specific synapse formation in the striatum. Nat Neurosci 15:215-23
Higley, Michael J; Gittis, Aryn H; Oldenburg, Ian A et al. (2011) Cholinergic interneurons mediate fast VGluT3-dependent glutamatergic transmission in the striatum. PLoS One 6:e19155
Giessel, Andrew J; Sabatini, Bernardo L (2011) Boosting of synaptic potentials and spine Ca transients by the peptide toxin SNX-482 requires alpha-1E-encoded voltage-gated Ca channels. PLoS One 6:e20939