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Defining the impact of newborn neurons in mouse olfactory bulb on neural homeostasis by combining optogenetics with in vivo imaging, Teilprojekt A05

Laufzeit: 01.01.2013 - 31.12.2016

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Teilprojekt A05:Defining the impact of newborn neurons in mouse olfactory bulb on neural homeostasis by combining optogenetics with in vivo imaging
In the adult mammalian brain, the neural network homeostasis is mainly sustained by plasticity on the subcellular level. However, two areas of the adult mammalian brain, the dentate gyrus (DG) and the olfactory bulb (OB), undergo constant network remodeling through the ongoing integration of newly generated neurons. The functional relevance of this...
Teilprojekt A05:Defining the impact of newborn neurons in mouse olfactory bulb on neural homeostasis by combining optogenetics with in vivo imaging
In the adult mammalian brain, the neural network homeostasis is mainly sustained by plasticity on the subcellular level. However, two areas of the adult mammalian brain, the dentate gyrus (DG) and the olfactory bulb (OB), undergo constant network remodeling through the ongoing integration of newly generated neurons. The functional relevance of this adult neurogenesis has been the focus of numerous studies in the past decade, indicating among others a critical role for sensory discrimination and learning and memory. Yet its functional impact on the respective neural circuits is only poorly understood due to the difficulty to reversibly, yet selectively activate or inhibit adult-generated neurons. In order to obtain insights into the role of adult-generated neurons at the circuit level, we combine here 2-photon Ca2+ imaging techniques with optogenetics and novel synaptic tracing tools to probe the specific impact of newborn neurons on the functional level. In aim I we will adapt viral tools for optogenetic actuators to allow for selective and reversible activation/inhibition of adult-born neurons. We will then conduct 2-photon Ca2+ imaging in acute brain slices to characterize the network response to activation/inhibition of newborn neurons during the course of their synaptic integration. In aim II we will employ a modified rabies virus to map and functionally study the presynaptic connectome of adult-generated neurons, both in the OB and the DG. Furthermore, we will assess whether the neural processing in the OB can be functionally modified by converting neural progenitors, normally generating predominantly GABAergic interneurons, to a glutamatergic neuron fate. In aim III, we will conduct in vivo Ca2+ imaging of the OB and specifically probe the impact of newborn OB neurons both on spontaneous and olfactory stimulus evoked network activity.
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