Estimating Information Processing in a Memory System: The Utility of Meta-analytic Methods for Genetics

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.

[1]  H. Bading,et al.  Requirement for Nuclear Calcium Signaling in Drosophila Long-Term Memory , 2013, Science Signaling.

[2]  D. Howells,et al.  Publication Bias in Reports of Animal Stroke Studies Leads to Major Overstatement of Efficacy , 2010, PLoS biology.

[3]  Jacob Cohen The earth is round (p < .05) , 1994 .

[4]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[5]  Ronald L. Davis,et al.  System-Like Consolidation of Olfactory Memories in Drosophila , 2013, The Journal of Neuroscience.

[6]  Andreas S. Thum,et al.  Differential potencies of effector genes in adult Drosophila , 2006, The Journal of comparative neurology.

[7]  Yoshinori Aso,et al.  The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers , 2009, Journal of neurogenetics.

[8]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[9]  J. Ioannidis Why Most Published Research Findings Are False , 2019, CHANCE.

[10]  J. Ioannidis Why Science Is Not Necessarily Self-Correcting , 2012, Perspectives on psychological science : a journal of the Association for Psychological Science.

[11]  Denton E. Morrison,et al.  The Significance Test Controversy , 1972 .

[12]  G. Cumming Understanding the New Statistics: Effect Sizes, Confidence Intervals, and Meta-Analysis , 2011 .

[13]  Ronald L. Davis,et al.  Spatiotemporal Rescue of Memory Dysfunction in Drosophila , 2003, Science.

[14]  Ronald L. Davis,et al.  Pharmacogenetic rescue in time and space of the rutabaga memory impairment by using Gene-Switch , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  J. Ioannidis,et al.  The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration , 2009, Annals of Internal Medicine [serial online].

[16]  Tim Tully,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2001, Nature.

[17]  M. S. Patel,et al.  An introduction to meta-analysis. , 1989, Health Policy.

[18]  Troy Zars,et al.  Learning and memory in Drosophila: behavior, genetics, and neural systems. , 2011, International review of neurobiology.

[19]  Martin Heisenberg,et al.  Extinction Antagonizes Olfactory Memory at the Subcellular Level , 2002, Neuron.

[20]  W. Quinn,et al.  Classical conditioning and retention in normal and mutantDrosophila melanogaster , 1985, Journal of Comparative Physiology A.

[21]  Ronald L. Davis,et al.  The Drosophila learning and memory gene rutabaga encodes a Ca 2+ calmodulin -responsive , 1992, Cell.

[22]  Ronald L. Davis,et al.  Traces of Drosophila Memory , 2011, Neuron.

[23]  Paul D. Ellis,et al.  The essential guide to effect sizes : statistical power, meta-analysis, and the interpretation of research results , 2010 .

[24]  M. Heisenberg,et al.  Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila , 2003, The Journal of Neuroscience.

[25]  G. Oehlert A note on the delta method , 1992 .

[26]  Ronald L. Davis,et al.  Roles for Drosophila mushroom body neurons in olfactory learning and memory. , 2006, Learning & memory.

[27]  Brian A. Nosek,et al.  Power failure: why small sample size undermines the reliability of neuroscience , 2013, Nature Reviews Neuroscience.

[28]  M. Heisenberg Mushroom body memoir: from maps to models , 2003, Nature Reviews Neuroscience.

[29]  W. Harris,et al.  Conditioned behavior in Drosophila melanogaster. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[30]  J. Crabbe,et al.  Genetics of mouse behavior: interactions with laboratory environment. , 1999, Science.

[31]  T. Kitamoto Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. , 2001, Journal of neurobiology.

[32]  R. D. Rosenkrantz,et al.  The significance test controversy , 1972, Synthese.

[33]  Loren J. Martin,et al.  Olfactory exposure to males, including men, causes stress and related analgesia in rodents , 2014, Nature Methods.

[34]  R. Davis,et al.  The Role of Drosophila Mushroom Body Signaling in Olfactory Memory , 2001, Science.

[35]  Maik C. Stüttgen,et al.  Computation of measures of effect size for neuroscience data sets , 2011, The European journal of neuroscience.

[36]  Gillian L. Currie,et al.  Meta-analysis of data from animal studies: A practical guide , 2014, Journal of Neuroscience Methods.

[37]  Andreas S. Thum,et al.  Behavioral/systems/cognitive Multiple Memory Traces for Olfactory Reward Learning in Drosophila Materials and Methods , 2022 .

[38]  S. Helene Richter,et al.  Environmental standardization: cure or cause of poor reproducibility in animal experiments? , 2009, Nature Methods.

[39]  Douglas G. Altman,et al.  Statistics with confidence: Confidence intervals and statistical guidelines . , 1990 .

[40]  S. Waddell,et al.  Sequential Use of Mushroom Body Neuron Subsets during Drosophila Odor Memory Processing , 2007, Neuron.

[41]  David J. Hand,et al.  Understanding The New Statistics: Effect Sizes, Confidence Intervals, and Meta‐Analysis by Geoff Cumming , 2012 .

[42]  M. Ramaswami,et al.  Endocytosis in Drosophila: progress, possibilities, prognostications. , 2001, Experimental cell research.

[43]  D. Curran‐Everett,et al.  The fickle P value generates irreproducible results , 2015, Nature Methods.

[44]  Scott Waddell,et al.  Shocking Revelations and Saccharin Sweetness in the Study of Drosophila Olfactory Memory , 2013, Current Biology.

[45]  Ronald L. Davis,et al.  Olfactory learning in Drosophila. , 2010, Physiology.

[46]  J. Ioannidis Why Most Published Research Findings Are False , 2005, PLoS medicine.

[47]  Gilles Laurent,et al.  Testing Odor Response Stereotypy in the Drosophila Mushroom Body , 2008, Neuron.

[48]  M Heisenberg,et al.  Localization of a short-term memory in Drosophila. , 2000, Science.

[49]  R. Davis,et al.  Tripartite mushroom body architecture revealed by antigenic markers. , 1998, Learning & memory.

[50]  S. Waddell,et al.  Drosophila olfactory memory: single genes to complex neural circuits , 2007, Nature Reviews Neuroscience.

[51]  M. Low,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2022 .

[52]  Andreas S. Thum,et al.  Consolidated and Labile Odor Memory Are Separately Encoded within the Drosophila Brain , 2012, The Journal of Neuroscience.

[53]  L. Abbott,et al.  Random Convergence of Olfactory Inputs in the Drosophila Mushroom Body , 2013, Nature.

[54]  Wanhe Li,et al.  Short- and Long-Term Memory in Drosophila Require cAMP Signaling in Distinct Neuron Types , 2009, Current Biology.