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VEGFD Downregulation in Hippocampal Area CA1: Effects on Dendritic Morphology of Pyramidal Neurons and Network Activity

Maurer, Jana

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Abstract

Neurons constitute the cellular basis of the nervous system and their activity generates most functions of the brain. Although, neurons exhibit highly diverse structures, their morphology comprises three main functional compartments. Dendrites are ramified structures and the major input side of neurons. Different input signals converge at the soma in order to generate action potentials. This output is transmitted through the axon to other neurons, thus creating complex neuronal networks. The morphology of dendritic arbors has a high impact on the connectivity and the electrical properties of neurons, determining input signals and their transmission and integration. It is therefore of great importance to study the link between dendritic morphology, electrical properties of single neurons and functions on the network level. By studying neurodegenerative diseases, it becomes clear that particularly the maintenance of the neuronal morphology is crucial for proper cognitive performance. Previous studies demonstrated that the growth factor VEGFD regulates the maintenance of the dendritic length in cultured neurons and of basal dendrites in the mouse hippocampus. Furthermore, VEGFD deficient mice show a long-term memory deficit, suggesting a link between altered dendritic morphology and cognitive function deficits. In this study, the regulatory effect of VEGFD on the branching of distinct dendritic compartments and the functional consequences of VEGFD loss both on a single cell level and on the level of network oscillations were investigated. Following the suppression of VEGFD in CA1 pyramidal neurons in vivo, detailed morphometric analyses, including basal and apical dendrites as well as spine density, confirmed that basal dendrites loose length and overall complexity. Interestingly, the apical dendrites increased in length and size. This elongation occurred in areas with a high density of synaptic inputs. The spine density in all areas remained unaltered, indicating a shift in input ratio between longer apical and smaller basal dendritic trees. Furthermore, the functional consequences of VEGFD loss on single cell level and on network oscillations were investigated. Single cell patch clamp recordings revealed no changes in passive membrane properties and action potential firing properties, apart from an increased input resistance. The in vivo electrical stimulation of two distinct input pathways to CA1 revealed no alterations in the synaptic input strength. The comparison of several network oscillations between knockdown mice and control animals revealed no differences. These surprising results indicate that changed dendritic morphology due to the loss of VEGFD has no impact on network oscillations, such as theta, gamma and SPW R, in different behavioral states like running, immobility and sleep.

Item Type: Dissertation
Supervisor: Draguhn, Prof. Dr. Andreas
Date of thesis defense: 4 December 2017
Date Deposited: 13 Dec 2017 08:38
Date: 2017
Faculties / Institutes: The Faculty of Bio Sciences > Dean's Office of the Faculty of Bio Sciences
Subjects: 570 Life sciences
Controlled Keywords: Hippocampus, Learning and memory, VEGFD
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