Ronald L. Davis, Ph.D.
Professor and Chair
Adjunct Professor - Department of Molecular and Cellular Biology and Department of Neuroscience, Baylor College of Medicine, Houston TX
Affiliate Professor - Department of Biological Sciences, Florida Atlantic University, Boca Raton, FL
Affiliate Professor - Florida Atlantic College of Medicine, Boca Raton, FL
Ph.D., University of California, Davis, 1979
Department of Neuroscience
130 Scripps Way C349
Jupiter, Florida 33458
We study memory formation at multiple levels of analysis and the disorders associated with memory dysfunction. At the molecular level, the goals are to understand the structure, regulation, evolution and biological function of genes required for normal memory formation. At the cellular level, the goal is to understand how the gene products mediate physiological changes after learning in the neurons that mediate behavior. An additional goal is to understand how alterations in neuronal physiology produce changes in communication with neighboring neurons that comprise the behavioral circuits. We also translate our basic science discoveries towards dissecting memory disorders in humans.
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 identified the products of these genes, such as the enzyme, cAMP phosphodiesterase encoded by dunce, and adenylyl cyclase encoded by rutabaga. These and other 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 are termed mushroom body cells. All of the genes discussed above are preferentially expressed in these neurons. Our current goals include understanding these and other genes 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. 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.
A recent and important discovery relates to the process of active forgetting. Our results indicate that chronic activity of dopaminergic neurons represents a signal to mushroom body neurons to forget previously encoded information. The topic of active forgetting is extremely well understudied in neuroscience and our discovery offers a window to capture a better understanding of this important function of the brain.
It is important to determine whether these genes 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. In addition, we have studied the genetics of susceptibility to bipolar disorder using a case:control experimental design. Through this study, we identified several genes associated with bipolar disorder and are currently focusing on a small number of these genes including PDE10A.
Cheng Y, Endo K, Wu K, Rodan AR, Davis RL (2001). Drosophila fasciclinII is required for the formation of odor memories for normal sensitivity to alcohol. Cell 105, 757-768.
McGuire SE, Le PT, Davis RL (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.
Awards, Recognition, Appointments, and Honors
McKnight Scholars Award in Neuroscience from the McKnight Foundation
Development Award in Neuroscience from the McKnight Foundation
NIH Academic Career Leadership Award
McKnight Neuroscience of Brain Disorders Awardee
NARSAD Distinguished Investigator Award
Ellison Medical Foundation Senior Scholar in Aging Award
Jacob Javitts Career Award from the National Institutes of Health