Role of Slit2 in PV neuron Development

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Authors

Rukundo, Pacifique

Issue Date

2023

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Thesis

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Alzheimer’s , Parvalbumin , Schizophrenia , Slit2 , Synapses

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Parvalbumin expressing interneurons (PV INs) are found in the dentate gyrus of the hippocampus, a region of the brain responsible for learning, memory, and navigation. PV INs are of paramount importance in regulating circuit function, such as controlling neuronal firing and circuit synchronicity. Additionally, PV INs are necessary for creating and maintaining gamma oscillation in the circuit. Alterations of PV IN connectivity have been linked to the pathophysiology of neurological diseases such as Schizophrenia and Alzheimer’s. Moreover, we know very little about the molecular mechanism that regulate PV INs connectivity. Previous studies of PV INs molecular makeups using Ribonucleic acid sequencing (RNA seq) shows that Slit2 transcripts are enriched in these cells. Although it has previously been shown that Slit2 protein is essential for neuronal migration, axon guidance and recently, excitatory synapse formation, little is known about how it affects PV INs development. In this work we aim to unravel whether Slit2 is important for inhibitory (PV INs) development in the Dentate Gyrus of the mouse hippocampus. We hypothesize that Slit2 is involved in regulating PV INs development, and synapse formation. To investigate this hypothesis, we used genetic and confocal techniques to determine how Slit2 deletion in young adolescent animals affects PV IN morphologies and synaptic connections. We have found that knocking out Slit2 has a slight effect on PV dendrites morphology. PV INs of Slit2 mutants have a smaller shell in the middle molecular layer of the hippocampus compared to controls, signifying a smaller projection in space. Moreover, there is a slight increase of dendritic spines in the mutants. Furthermore, knocking out Slit2 increases the number of inhibitory inputs on PV INs mutants. Overall, we found Slit2 plays a role in regulating PV INs connectivity in young adolescent animals. Especially, inhibitory synapse formation on PV INs’ dendrites.

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Creative Commons Attribution-NoDerivatives 4.0 United States

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