Kainate Receptors in the Development of Adult-born Dentate Granule Cells in the Hippocampus

Zhu, Yiwen

doi:https://doi.org/10.21985/n2-eaem-3k83

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Kainate Receptors in the Development of Adult-born Dentate Granule Cells in the Hippocampus

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In the adult hippocampus of many mammalian species, populations of newborn dentate granule cells (DGCs) are continuously generated and undergo subsequent activity-dependent neuronal maturation and incorporation into the preexisting hippocampal circuitry. Increasing evidence has demonstrated that these young adult-born DGCs (abDGCs) participate in numerous cognitive and affective processes such as pattern separation, acquisition and retrieval of hippocampal-dependent memories, and stress responses. Therefore, the mechanisms that control the functional properties of maturing abDGCs are of relevance to multiple neurocognitive processes. Both inhibitory and excitatory neurotransmitter receptors can influence maturation and survival of adult-born neurons in the dentate gyrus; yet how these two neurotransmitter systems affect integration of new neurons into the existing circuitry is still not fully characterized. In this thesis project I demonstrate that glutamate receptors of the kainate receptor (KAR) subfamily are expressed in young abDGCs and that, through potential interaction with GABAergic signaling mechanisms, KARs regulate the functional properties of abDGCs during a critical period of their development. Both the measured intrinsic properties and synaptic connectivity of young abDGCs were altered after ablation of GluK2. Timed GluK2 loss in a cohort of young abDGCs in mice disrupted their performance in a spatial discrimination task but not in other hippocampal-dependent tasks. Together my study has revealed a novel and important role of KARs in the proper functional development of newborn neurons and further highlighted the tight cooperation between excitatory and inhibitory neurotransmitter signaling in the hippocampus.

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