The importance of an activated hippocampal-VTA loop for functional connectivities of the rat hippocampus

The hippocampus plays important roles in the consolidation of learning directed processes. In addition, the mesolimbic system is one of the most central systems for modulating learningrelated plasticity in the brain. Hippocampal activity is indirectly linked to the activity of dopaminergic neurons in the ventral tegmental area and controls by that the function of various structures in the mesolimbic system, such as the nucleus accumbens, the amygdala, the medial prefrontal cortex and eventually the hippocampus itself. Electrical stimulation of one major hippocampal output system, the fimbria-fornix fibers, in combination with functional magnetic resonance imaging (fMRI) or fast scan cyclic voltammetry (FSCV) will reveal how altered hippocampal activity drives mesolimbic dopaminergic activity and how this increased mesolimbic dopaminergic activity in turn modifies hippocampal activity. Thus, how an activation of the hippocampus-VTA loop affects brain wide neuronal networks. For that, a multimodal imaging approach is employed to examine global and local changes in neuronal activities that occur during defined electrical hippocampal fimbria stimulation in sedated rats. Changes in global neuronal network activity during electrical stimulation of the hippocampal fimbria fibers will be visualized by fMRI and local neurochemical changes will be monitored by FSCV. Additionally, engineered designer receptors exclusively activated by designer drugs (DREADD) will be used to selectively silence dopaminergic neurons in the VTA to examine how a disturbed hippocampal-VTA loop modifies functional interactions of the hippocampal with various subcortical and cortical structures.

Laufzeit:

01.06.2018 – 31.05.2021