Neuromodulatory neurons project to a wide range of target areas and adjust neuronal circuit function by modifying neuronal properties, synaptic transmission, and neuronal plasticity. Neuromodulators such as dopamine are implicated in various neurological disorders such as Schizophrenia and addiction. Despite detailed insights into the molecular and cellular actions of neuromodulators, their concerted effects on circuit function are poorly understood, mainly because they have complex combinations of effects on individual circuit components, and because computational functions of cortical circuits are largely unresolved. An important neuromodulator involved in many neural disorders is dopamine (DA). To uncover fundamental principles and mechanisms by which DA modulates cortical computations, we will first analyze effects of DA on odor processing and memory storage in the zebrafish homolog of olfactory cortex (telencephalic area Dp). Using optogenetic manipulations in combination with patch clamp recordings and 2-photon calcium imaging we will determine the functional connectivity and plasticity effects of DA input from specific clusters of DA neurons on circuit function in Dp. These experiments will reveal the influence of DA input on the processing and storage of odor information. Moreover, they are likely to provide insights into the cellular and synaptic mechanisms underlying memory storage by auto-associative neuronal networks. To causally link the modulatory effects of DA with behavioral effects, we will manipulate DA input during olfactory learning and memory recall by opto- and pharmacogenetic approaches. The results are expected to be of fundamental relevance for understanding neuromodulatory systems and to have direct implications for treatments of neurological diseases such as schizophrenia and drug addiction.
Field of science
- /medical and health sciences/clinical medicine/psychiatry/schizophrenia
- /medical and health sciences/basic medicine/neurology
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