Biology subjects

Adam Claridge-Chang

Publications and source records attributed to Adam Claridge-Chang.

3 recordsLinked to original sources

bioRxiv2015

Drosophila learn efficient paths to a food source

Elucidating the genetic, and neuronal bases for learned behavior is a central problem in neuroscience. A leading system for neurogenetic discovery is the vinegar fly Drosophila melanogaster; fly memory research has identified genes and circuits that mediate aversive and appetitive learning. However, methods to study adaptive food-seeking behavior in this animal have lagged decades behind rodent feeding analysis, largely due to the challenges presented by their small scale. There is currently no method to dynamically control flies access to food. In rodents, protocols that use dynamic food delivery are a central element of experimental paradigms that date back to the influential work of Skinner. This method is still commonly used in the analysis of learning, memory, addiction, feeding, and many other subjects in experimental psychology. The difficulty of microscale food delivery means this is not a technique used in fly behavior. In the present manuscript we describe a microfluidic chip integrated with machine vision and automation to dynamically control defined liquid food presentations and sensory stimuli. Strikingly, repeated presentations of food at a fixed location produced improvements in path efficiency during food approach. This shows that improved path choice is a learned behavior. Active control of food availability using this microfluidic system is a valuable addition to the methods currently available for the analysis of learned feeding behavior in flies.

Animal Behavior and Cognition↗

bioRxiv2015

Concordance and incongruence in preclinical anxiety models: systematic review and meta-analyses

Rodent defense behavior assays have been widely used as preclinical models of anxiety to study possibly therapeutic anxiety-reducing interventions. However, some proposed anxiety-modulating factors--genes, drugs and stressors--have had discordant effects across different studies. To reconcile the effect sizes of purported anxiety factors, we conducted systematic review and meta-analyses of the literature on ten anxiety-linked interventions, as examined in the elevated plus maze, open field and light-dark box assays. Diazepam, 5-HT1A receptor gene knockout and overexpression, SERT gene knockout and overexpression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1 were selected for review. Eight interventions had statistically significant effects on rodent anxiety, while Htr1a overexpression and Crh knockout did not. Evidence for publication bias was found in the diazepam, Htt knockout, and social isolation literatures. The Htr1a and Crhr1 results indicate a disconnect between preclinical science and clinical research. Furthermore, the meta-analytic data confirmed that genetic SERT anxiety effects were paradoxical in the context of the clinical use of SERT inhibitors to reduce anxiety.\n\nHighlightsO_LIMeta-analysis shows eight rodent anxiety factors have at least moderate effects.\nC_LIO_LIPublication bias affects four of the anxiety interventions.\nC_LIO_LIPreclinical rodent anxiety results appear disconnected from clinical efforts.\nC_LIO_LISerotonin transporter gene lesion effects are paradoxical with reuptake inhibitors clinical use.\nC_LI

Animal Behavior and Cognition↗

bioRxiv2015

Estimating information flow through a memory system: the utility of meta-analytic methods for genetics

Critics of significance testing claim that this statistical framework promotes discrepancies by using arbitrary thresholds () to impose reject/accept dichotomies on continuous data, which is not reflective of the biological reality of quantitative phenotypes. Here we explore this idea and evaluate an alternative approach, demonstrating the potential for meta-analysis and related estimation methods to resolve discordance generated by the use of traditional significance tests. We selected a set of behavioral studies proposing differing models of the physiological basis of Drosophila olfactory memory and used systematic review and meta-analysis approaches to define the true role of lobular specialization within the brain. The mainstream view is that each of the three lobes of the Drosophila mushroom body play specialized roles in short-term aversive olfactory memory [1-5], but a number of studies have made divergent conclusions based on their discordant experimental findings [6-8]. Multivariate meta-regression models revealed that short-term memory lobular specialization is not in fact supported by the data, and identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. Our findings demonstrate that 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.

Neuroscience↗