Lab for Neural Circuits and Olfactory Perception
One of the major goals of neuroscience research is to understand how neural circuits encode information and support behavior, learning and memory. To answer this question requires us to relate neural activity to perception. Using the olfactory system of the fruit fly, Drosophila melanogaster, and a multidisciplinary approach which includes in vivo electrophysiology and functional imaging, optogenetics, thermogenetics and behavior experiments, we probe the neuronal codes underlying olfaction, manipulate them and examine the effects these manipulations have on behavior. In addition, we use the same techniques to understand the molecular basis of brain disorders and its effects on neural circuits’ connectivity and activity.
Neural temporal codes have come to dominate our way of thinking on how information is coded in the brain. When precise spike timing is found to carry information, the neural code is defined as a temporal code. In spite of the importance of temporal codes, whether behaving animals actually use this type of coding is still an unresolved question. To date studying temporal codes was technically impossible due to the inability to manipulate spike timing in behaving animals. However, very recent developments in optogenetics solved this problem. Despite these modern tools, this key question is very difficult to resolve in mammals, because the meaning of manipulating a part of a neural circuit without knowledge of the neural activity of all the neurons involved in the coding is unclear.
The fly is an ideal model system to study temporal codes because its small number of neurons allows for complete mapping of the neural activity of all the neurons involved. Since temporal codes are suggested to be involved in olfactory intensity coding, we study this process. For this we device a multidisciplinary approach of electrophysiology, functional imaging and behavior.
Schizophrenia, a highly heritable disease, is subject to intensive study. Yet, the genetic and neuronal mechanisms underlying this disorder are poorly understood. Treating schizophrenia is mainly achieved by antipsychotic drugs. These drugs exert their effects mainly through blockade of dopaminergic receptors and are used for over 60 years. However, for many patients the efficacy is poor. New drugs, based on other target molecules, had not been developed because of the poor understanding of the mechanisms which underlie schizophrenia. At present, there are over 1000 candidate genes associated with schizophrenia and for most of these polymorphisms/mutations’ the effects in the central nervous system are unknown. Using current methodology and vertebrate model systems, screening the function of so many genes is extremely difficult. However, the Drosophila model system offers the ability to perform large scale genetic screens and to uncover the mechanisms underlying schizophrenia. This is because of its extensive genetic toolbox, in vivo access to a developed brain capable of rich behaviour and yet which has fairly low complexity. We express human genes associated with schizophrenia in the Drosophila brain and examine the effects these genes have on behaviour and neural activity in a well-defined and characterized neural circuits.