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Function of dopaminergic neurons in neuronal circuits of the zebrafish olfactory system

English title Function of dopaminergic neurons in neuronal circuits of the zebrafish olfactory system
Applicant Zhang Schärer Yanping
Number 122829
Funding scheme Marie Heim-Voegtlin grants
Research institution Friedrich Miescher Institute for Biomedical Research
Institution of higher education Institute Friedrich Miescher - FMI
Main discipline Neurophysiology and Brain Research
Start/End 01.02.2009 - 31.01.2011
Approved amount 231'540.00
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Keywords (6)

dopamine; olfactory system; zebrafish; 2-photon imaging; channelrhodopsin; halorhodopsin

Lay Summary (English)

Lead
Lay summary
Dopaminergic (DA) neurons in the vertebrate brain are localized in conserved clusters, often project over long distances, and are thought to modulate the functions of neuronal circuits in their target areas. Changes in the DA system have long been associated with a number of important human diseases, ranging from Parkinson's disease and schizophrenia to addiction. In the normal brain, dopamine is commonly associated with the pleasure system and is released by rewarding experiences. When a reward is greater than expected, DA neurons in the midbrain increase their firing rate and the desire or motivation towards the reward is enhanced, indicating that DA neurons encode reward expectancy. At the cellular level, DA acts not only as a primary neurotransmitter but also as a modulator of synaptic transmission and plasticity. Despite insights into the cellular and behavioral functions of DA, however, a precise understanding of the mechanisms by which dopamine modulates brain functions remains elusive. Manipulations of the DA system have heavily relied on pharmacological interventions, which offer little spatial and temporal precision. Moreover, effects of DA at the cellular and systems level are typically studied separately under very different experimental conditions. In this research project, I will combine advanced optical and electrophysiological measurements to record neuronal activity patterns in the intact brain with opto-genetic methods to manipulate DA neurons with high spatial and temporal precision. This approach takes advantage of the zebrafish, a small vertebrate model system that permits the analysis of neuronal functions at multiple levels in the intact brain. In vivo multiphoton calcium imaging and electrophysiological recordings will be used to measure the responses to odor stimulation. I will specifically analyze the role of DA input for the function and plasticity of neuronal circuits in the higher olfactory system. The results are expected to provide fundamental insights into the mechanisms underlying the functions and dysfunctions of the DA system.
Direct link to Lay Summary Last update: 21.02.2013

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Abstract

The modulatory aminergic neurontransmitter dopamine (DA) has been implicated in important brain functions such as reward learning and plays an essential role in multiple neurological diseases including Parkinson’s disease, schizophrenia and drug addiction. The mechanisms underlying DA functions and dysfunctions remain, however, poorly understood, mainly because it has been difficult to relate effects of DA at the cellular level to the complex functions of neuronal circuits. I will therefore use a small vertebrate model system, the zebrafish, to analyze effects of DA on activity patterns in the intact brain with cellular resolution. In vivo multiphoton imaging, electrophysiology and molecular genetics will be combined to study the role of DA neurons for the function and plasticity of neuronal circuits in the olfactory system. Genetic tools will be used to manipulate DA neuron activity in a temporally and spatially controlled manner. In vivo multiphoton calcium imaging and electrophysiological recordings will be used to measure the responses to odor stimulation in olfactory bulb and in higher olfactory centers. The long-term goal of this project is to obtain a better understanding how DA inputs modulate neural circuit function and plasticity.
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