Ronald Davis, PhD

Professor
Department of Neuroscience
Florida Campus


 Email

Scripps Research Joint Appointments

Faculty, Graduate Program

Other Joint Appointments

Adjunct Professor, Dept. of Molecular & Cellular Biology, Baylor College of Medicine, Houston TX
Adjunct Professor, Dept. of Neuroscience, Baylor College of Medicine, Houston TX
Adjunct Professor, Dept. of Biological Sciences, Florida Atlantic University

Research Focus

We are interested in the brain and how memories are formed, stabilized, and retrieved. We are also interested in the human diseases that affect learning and memory, including Alzheimer’s, schizophrenia, bipolar disorder, autism, and ADHD. We study learning and memory at the genetic level to understand the structure, regulation, evolution and biological function of genes that are required for normal learning and memory. Studies at the cellular level help us to understand how the gene products involved in learning and memory mediate physiological changes in the neurons that encode memories. We also focus effort at the level of anatomy to understand the pathways of information flow in the brain for normal learning to occur, and at the behavioral level to probe the complexities of memory formation.

Numerous genes important for learning in Drosophila have been studied extensively. Some of these include dunce, rutabaga, DCO, and CREB. Flies defective in the expression of any of these genes exhibit poor memory formation for olfactory conditioning tasks. Molecular cloning has demonstrated that dunce codes for the enzyme, cAMP phosphodiesterase; rutabaga codes for adenylyl cyclase; DCO codes for the catalytic subunit of protein kinase A, and CREB a transcription factor that is phosphorylated and activated by protein kinase A. These results demonstrate that the cAMP signaling system is critical for altering the physiological state of the neurons that mediate this type of learning. Other studies have shown that a family of proteins called 14-3-3 are involved in learning along with interesting cell adhesion molecules of the integrin family and the immunoglobulin superfamily. Moreover, we have studied several biogenic amine receptors, including dopamine receptors that are involved in the acquisition of initial memories. By studying the expression of these genes, the neurons that mediate learning have been identified. These include the mushroom body cells. All of the genes discussed above are preferentially expressed in these neurons. Our current goals include understanding these and other genes and the role of mushroom body neurons in further detail.

We have developed a powerful new imaging technology that allows us to visualize changes that occur in the brain of Drosophila due to learning. Using this technology, we have discovered several of these changes, or memory traces, in different neurons of the brain (Figure). Some changes occur immediately after learning and persist for only a few minutes; others form with a delay of up to several hours and likely persist for days. Thus, behavioral memory may be due to the effects of multiple memory traces, each controlling behavior over discrete windows of time after learning.

It is important to determine whether the genes identified from model systems like Drosophila also serve mammalian behavior. To approach this, we have cloned mouse homologs of some of the aforementioned genes and have genetically studied their role in mammalian behavior. Of high interest are the knockouts of certain integrin genes, which produce an impairment of working memory without affecting other types of memory. These knockouts may be important models for human brain diseases that affect working memory including Alzheimer’s Disease, schizophrenia, autism, and ADHD.


Education

Ph.D. (Genetics), University of California, Davis, 1979
M.S. (Genetics), University of California, Davis, 1975
B.S. (Zoology), Brigham Young University, 1974

Professional Experience

2017-2018 Co-Chair, Neuroscience, Scripps Research
2009-2017 Chairman, Neuroscience, Scripps Research
2007-2009 Director, Center for Memory & Learning, Baylor College of Medicine
1998-2009 Professor, Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine
1993-2009 Professor, Departments of Molecular & Cellular Biology; Genetics; and Neuroscience, Baylor College of Medicine
1999-2007 Vice Chair for Research, Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine
1991-1993 Senior Staff Scientist, Cold Spring Harbor Laboratory
1991-1993 Adjunct Associate Professor of Cell Biology, Baylor College of Medicine
1987-1991 Associate Professor of Neuroscience, Baylor College of Medicine
1987-1991 Associate Professor of Cell Biology, Baylor College of Medicine
1987-1987 Associate Professor of Biochemistry, Michigan State University
1983-1987 Assistant Professor of Biochemistry, Michigan State University
1979-1982 Postdoctoral Fellow in Molecular Biology with Dr. Norman Davidson, California Institute of Technology

Awards & Professional Activities

Damon Runyon-Walter Winchell Postdoctoral Fellowship
National Institutes of Health Postdoctoral Fellowship
McKnight Scholars Award in Neuroscience
NIH Research Career Development Award
McKnight Foundation Development Award
R. P. Doherty-Welch Chair in Science at Baylor College of Medicine Student Choice Award in Teaching at Baylor College of Medicine
Michael E. DeBakey Excellence in Research Award
Academic Career Leadership Award
McKnight Neuroscience of Brain Disorders Award
NARSAD Distinguished Investigator Award
Ellison Medical Foundation Senior Scholar in Aging

Selected References

All Publications

McGuire, S.E., Le, P.T., Davis, R.L. (2001). The role of Drosophila mushroom body signaling in olfactory memory. Science 10, 1130-1134.

McGuire, S.E., Le, P.T., Osborn, A.J., Matsumoto, K., and Davis, R.L. (2003). Spatio-temporal Rescue of Memory Dysfunction in Drosophila. Science 302, 1765-1768.

Yu, D., Ponomarev, A. and Davis, R.L. (2004). Altered representation of the spatial code for odors after olfactory classical conditioning: memory trace formation by synaptic recruitment. Neuron 42, 437-449.

Davis, R.L. (2004) Olfactory learning. Neuron, 44, 31-48.

Davis, R.L. (2005). Olfactory memory formation in Drosophila: From molecular to systems neuroscience. Ann. Rev Neurosci. 28, 275-302.

Yu, D., Keene A.C., Srivatsan, A., Waddell, S., and Davis, R.L. (2005). Drosophila DPM neurons form a delayed and branch-specific memory trace after olfactory classical conditioning. Cell 123, 945-957.

Chan, C.S., Weeber, E.J., Zong, L., Fuchs, E., Sweatt, J.D., and Davis, R.L. (2006). b1-Integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory. J. Neurosci. 26, 223-233.

Liu, X., Krause, W.C., and Davis, R.L. (2007). GABAA receptor RDL inhibits Drosophila olfactory associative learning. Neuron, 56, 1090-102.

Liu, X. and Davis, R.L. (2009). The GABAergic anterior paired lateral neuron of Drosophila suppresses and is suppressed by olfactory learning. Nat. Neurosci. 12, 53-59.

Tomchik, S. and Davis, R.L. (2009). Dynamics of learning-related cAMP signaling and stimulus integration in the Drosophila olfactory pathway. Neuron 64, 510-521.

Akalal, D.B.G., Yu, D., and Davis, R.L. (2010). A late-phase, long-term memory trace forms in the γ neurons of Drosophila mushroom bodies after olfactory classical conditioning. J Neurosci. 30, 16699-16708.

Chan, C.-S., Chen, H., Bradley, A., Dragatsis, I., Rosenmund, C.,  and Davis, R.L. (2010). α8-integrins are required for hippocampal long-term potentiation but not for hippocampal-dependent learning. Genes, Brain and Behavior 9, 402-410

Tan, Y., Yu, D., Pletting, J., and Davis, R.L. (2010). Gilgamesh is required for rutabaga-independent olfactory learning in Drosophila. Neuron 67, 810-820. 

Davis, R.L. (2010). Rac in the Act of Forgetting.  Cell 140, 456-458.

Buchanan, M. E. and Davis, R.L. (2010). A distinct set of Drosophila brain neurons required for NF1-dependent learning and memory. J. Neurosci. 30, 10135-10143.

Akalal, D.B.G., Yu, D., Davis, R.L. (2011). The Long-Term Memory Trace Formed in the Drosophila α/β Mushroom Body Neurons is abolished in Long-Term Memory Mutants. J Neurosci. 31, 5643-5647.

Davis, R.L. (2011). Traces of Drosophila Memory.  Neuron 70, 8-19.

Yu, D., Davis, R.L.  “Functional imaging of antennal lobe neurons in Drosophila with synapot-pHluorin.”  In Genetically Encoded Functional Indicators.  Ed., J.-R. Martin. NeuroMethods Springer Science (New York). Volume 72, 2012, pp 71-81.

Mortillo, S., Elste1, A., Ge, Y., Patil, S.B., Hsiao, K., Huntley, G.W., Davis, R.L., Benson, D.L. (2011). Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic ß1-integrin.  Journal of Comparative Neurology.  J Comp Neurol. DOI 10.1002/cne.23033 [Epub ahead of print]

Berry J.A., Cervantes-Sandoval, I., Nicholas, E.P., Davis, R.L. (2012). Dopamine is required for learning and forgetting in Drosophila. Neuron 74, 530-542. 

Tonoki, A. and Davis, R.L. (2012). Aging impairs intermediate-term behavioral memory by disrupting the dorsal paired medial neuron memory trace. Proc. Natl. Acad. Sci. USA. 109, 6319-6324. Proc. Natl. Acad. Sci. USA. 109, 6319-6324.

Ning, L., Tian, L, Smirnov, S., Llano, O., Vihinen, H., Vick, K., Davis, R.L., Rivera, C., and Gahmberg, C.G. (2012). Interactions between intercellular adhesion molecule-5 (ICAM-5) and ß1 integrins regulate neuronal synapse formation.  J Neurosci.

Cervantes-Sandoval, I. and Davis, R.L. (2012). Distinct Traces for Appetitive versus Aversive Olfactory Memories in DPM Neurons of Drosophila. Curr. Biol. 22, 1247-1252.

Tomchik S and Davis RL. (2013). “Drosophila Memory Research Through Four Eras: Genetic, Molecular Biology, Neuroanatomy, and Systems Neuroscience.” In Invertebrate Learning and Memory Vol 22. Eds., Menzel, R. and Benjamin, P. Academic Press (San Diego).

Davis, R.L. and Giurfa, M. (2012).  “Mushroom-body memories: An obituary prematurely written?”  Curr. Biol. 22, R272-275.

McDonald, M-L., MacMullen, C., Liu, D.J., Leal, S.M., and Davis, R.L. (2012).  Genetic association of cyclic AMP signaling genes with bipolar disorder. Translational Psychiatry, doi:10.1242/jcs.106674.

Tomchik, S. and Davis, R.L. (2013). “Drosophila Memory Research Through Four Eras: Genetic, Molecular Biology, Neuroanatomy, and Systems Neuroscience.” In Invertebrate Learning and Memory. Eds., Menzel, R. and Benjamin, P. Vol 22, release date 13 July 2013.

Cervantes-Sandoval, I., Martin-Peña, A., Berry, J.A., Davis, R.L. (2013) System-like consolidation of olfactory memories in Drosophila. J. Neuroscience 33, 9846-9854.

Tan, Y., Yu, D., Wilson, C., and Davis, R.L. (2013). Wnt signaling is required for long-term memory formation in Drosophila.  Cell Rep. 4, 1082-1089.

Yu, D., Tan, Y., Cervantes-Sandoval, I., Harbaran, S., and Davis, R.L. (2013). Elongator is required for long-term memory formation in Drosophila

Davis, R.L. (2013). Spermidine cures flies of senior moments. Nature Neurosci. 16, 1363-4. 

Chihara, T., Kitabayashi, A,  Morimoto, M., Takeuchi, K., Masuyama, K., Tonoki, A., Davis, R.L., Wang, J., and Miura, M. (2014). Caspase inhibition of select olfactory neurons restores innate attraction behavior in aged Drosophila. PLoS Genetics 10(6):e1004437.

Berry, J.A. and Davis, R.L. (2014) Active forgetting of olfactory memories in Drosophila. Prog Brain Res 208, 39-62.

Guven-Ozkan, T. and Davis, R.L. (2014). Functional neuroanatomy of Drosophila olfactory memory formation. Learn Mem 21, 519-526.

Berry, J.A., Cervantes-Sandoval, I.,
 Davis, R.L. (2014). Sleep facilitates memory by blocking dopamine neuron mediated forgetting. Prog Brain Res. 208, 39-62. 

Tonoki, A., and Davis, R.L. (2015). Aging impairs protein synthesis-dependent long-term memory in DrosophilaJ Neuros. 35, 1173-1180.

Busto, G.U., Guven-Ozkan, T., Fulga, T.A., Van Vactor, D., Davis, R.L. (2015).  Behavioral screening identifies five microRNAs promoting and inhibiting olfactory learning or memory formation in Drosophila melanogaster. Genetics 200, 569-580.

Walkinshaw, E., Gai, Y., Farkas, C., Richter, D., Nicholas, E., Keleman, K., and Davis, R.L. (2015). Drosophila RNAi screen identifies genes that promote and inhibit olfactory memory formation. Genetics 199, 1173-1182. 

Berry JA, Cervantes-Sandoval I, Chakraborty M, Davis RL. (2015). Sleep facilitates memory by blocking dopamine neuron mediated forgetting. Cell 161, 1656-1667. 

Davis RL. (2015). Snapshot: Olfactory classical conditioning of Drosophila. Cell 163, 524-524e1. 

MacMullen CM, Vick K, Pacifico R, Fallahi-Sichani MS and Davis RL. (2015). Novel, primate specific PDE10A isoform highlights gene expression complexity in human striatum with implications on the molecular pathology of bipolar disorder. Translational Psychiatry 6, e742; doi:10.1038/tp.2016.3.

Guven-Ozkan T, Busto GU, Schutte SS, Cervantes-Sandoval I, O’Dowd D and Davis RL. (2016). MiR-980 is a memory suppressor microRNA that regulates the autism-susceptibility gene, A2bp1. Cell Reports 14,1698-1709.

Gai Y, Liu Z, Cervantes-Sandoval I and Davis RL. (2016). Drosophila SLC22A transporter is a memory suppressor gene that influences cholinergic neurotransmission to the mushroom bodies. Neuron 90, 581-595.

Cervantes-Sandoval I, Chakraborty M, MacMullen C and Davis RL. (2016). Scribble scaffolds a signalosome for active forgetting. Neuron 90, 1230-1242.

Drago I and Davis RL. (2016). Inhibiting the mitochondrial calcium uniporter during development impairs memory in adult Drosophila. Cell Reports 16, 2763-2776.

Busto GU, Guven-Ozkan T, Chakraborty M and Davis RL. (2016). Developmental inhibition of miR-iab8-3p disrupts mushroom body neuron structure and adult learning ability. Developmental Biology 419, 237-249.

Busto GU, Guven-Ozkan T and Davis RL. (2017). MicroRNA function in Drosophila memory formation. Current Opinion Neurobiology 43, 15-24.

MacMullen CM, Fallahi MS and Davis RL. (2017). Novel PDE10A transcript diversity in the human striatum: insights into gene complexity, conservation and regulation. Gene 606, 17-24.

Cervantes-Sandoval I, Phan A, Chakraborty M and Davis RL. (2017). Reciprocal synapses between mushroom body and dopamine neurons form a positive feedback loop required for learning. Elife May 10;6. pii: e23789. doi: 10.7554/eLife.23789.

Davis RL and Zhong Y. (2017). The biology of forgetting - A Perspective. Neuron 95, 490-503.

Himmelreich S, Masuho I, Berry JA, MacMullen C, Skamangas N, Martemyanov KA, Davis RL. (2017). Dopamine receptor DAMB signals via Gq to mediate forgetting in Drosophila. Cell Reports 21, 2074-2081.

Muntean BS, Zucca S, MacMullen CM, Iwamoto H, Blakely RD, Davis RL and Martemyanov KM. (2017) Interrogating the spatiotemporal landscape of neuromodulatory GPCR signaling by real-time imaging of cAMP in intact neurons and circuits. Cell Reports 22, 255-268.

Yu D, Tan Y, Chakraborty M, Tomchik S and Davis RL. (2017) Elongator complex is required for long-term olfactory memory formation in Drosophila. Learning and Memory 25, 183-196.

Spicer TP, Hubbs C, Vaissiere T, Collia D, Rojas C, Kilinc M, Vick K, Madoux F, Baillargeon P, Shumate J, Martemyanov KA, Page DT, Puthanveettil S, Hodder P, Davis R, Miller CA, Scampavia L, Rumbaugh G. (2017) Improved scalability of neuron based phenotypic screening assays for therapeutic discovery in neuropsychiatric disorders. Molecular Neuropsychiatry 3, 141-150.

Crittendon JA, Skoulakis EMC, Goldstein ES and Davis RL. (2018) Drosophila mef2 is essential for normal mushroom body and wing development. Biology Open 7(9) pii: bio035618. doi: 10.1242/bio.035618.

Kepiro M, Varkuti BH and Davis RL. (2018) High content, phenotypic assays and screens for compounds modulating cellular processes in primary neurons. Methods Enzymol. 610, 219-250.

Berry JA, Phan Anna and Davis RL. (2018) Dopamine neurons mediate learning and forgetting through bidirectional modulation of a memory trace. Cell Reports 25, 651-662.

Pacifico R, MacMullen CM, Walkinshaw E, Zhang X and Davis RL. (2018) Brain transcriptome changes in the aging Drosophila melanogaster accompany olfactory memory performance deficits. PLoS One 13, 12:e0209405.

Phan A, Thomas CI, Chakraborty M, Berry JA, Kamasawa N and Davis RL. (2019) Stromalin constrains memory acquisition by developmentally limiting synaptic vesicle pool size. Neuron 101, 103-118.


Links

Department of Neuroscience