Dataset Information

Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis.

ABSTRACT: Newborn dentate granule cells (DGCs) are continuously generated in the adult brain. The mechanism underlying how the adult brain governs hippocampal neurogenesis remains poorly understood. In this study, we investigated how coupling of pre-existing neurons to the cerebrovascular system regulates hippocampal neurogenesis. Using a new in vivo imaging method in freely moving mice, we found that hippocampus-engaged behaviors, such as exploration in a novel environment, rapidly increased microvascular blood-flow velocity in the dentate gyrus. Importantly, blocking this exploration-elevated blood flow dampened experience-induced hippocampal neurogenesis. By imaging the neurovascular niche in combination with chemogenetic manipulation, we revealed that pre-existing DGCs actively regulated microvascular blood flow. This neurovascular coupling was linked by parvalbumin-expressing interneurons, primarily through nitric-oxide signaling. Further, we showed that insulin growth factor 1 signaling participated in functional hyperemia-induced neurogenesis. Together, our findings revealed a neurovascular coupling network that regulates experience-induced neurogenesis in the adult brain.

SUBMITTER: Shen J

PROVIDER: S-EPMC6728189 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis.

Shen Jia J Wang Depeng D Wang Xinxing X Gupta Shashank S Ayloo Bhargav B Wu Song S Prasad Paras P Xiong Qiaojie Q Xia Jun J Ge Shaoyu S

Neuron 20190627 5

Newborn dentate granule cells (DGCs) are continuously generated in the adult brain. The mechanism underlying how the adult brain governs hippocampal neurogenesis remains poorly understood. In this study, we investigated how coupling of pre-existing neurons to the cerebrovascular system regulates hippocampal neurogenesis. Using a new in vivo imaging method in freely moving mice, we found that hippocampus-engaged behaviors, such as exploration in a novel environment, rapidly increased microvascula ...[more]

PMID: 31257104

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Project description:The hippocampus is one of the most widely studied areas in the brain because of its important functional role in memory processing and learning, its remarkable neuronal cell plasticity, and its involvement in epilepsy, neurodegenerative diseases, and psychiatric disorders. The hippocampus is composed of distinct regions; the dentate gyrus, which comprises mainly granule neurons, and Ammon's horn, which comprises mainly pyramidal neurons, and the two regions are connected by both anatomic and functional circuits. Many different mRNAs and proteins are selectively expressed in the dentate gyrus, and the dentate gyrus is a site of adult neurogenesis; that is, new neurons are continually generated in the adult dentate gyrus. To investigate mRNA and protein expression specific to the dentate gyrus, laser capture microdissection is often used. This method has some limitations, however, such as the need for special apparatuses and complicated handling procedures. In this video-recorded protocol, we demonstrate a dissection technique for removing the dentate gyrus from adult mouse under a stereomicroscope. Dentate gyrus samples prepared using this technique are suitable for any assay, including transcriptomic, proteomic, and cell biology analyses. We confirmed that the dissected tissue is dentate gyrus by conducting real-time PCR of dentate gyrus-specific genes, tryptophan 2,3-dioxygenase (TDO2) and desmoplakin (Dsp), and Ammon's horn enriched genes, Meis-related gene 1b (Mrg1b) and TYRO3 protein tyrosine kinase 3 (Tyro3). The mRNA expressions of TDO2 and Dsp in the dentate gyrus samples were detected at obviously higher levels, whereas Mrg1b and Tyro3 were lower levels, than those in the Ammon's horn samples. To demonstrate the advantage of this method, we performed DNA microarray analysis using samples of whole hippocampus and dentate gyrus. The mRNA expression of TDO2 and Dsp, which are expressed selectively in the dentate gyrus, in the whole hippocampus of alpha-CaMKII+/- mice, exhibited 0.037 and 0.10-fold changes compared to that of wild-type mice, respectively. In the isolated dentate gyrus, however, these expressions exhibited 0.011 and 0.021-fold changes compared to that of wild-type mice, demonstrating that gene expression changes in dentate gyrus can be detected with greater sensitivity. Taken together, this convenient and accurate dissection technique can be reliably used for studies focused on the dentate gyrus.

Dataset Information

Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis.

Publications

Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis.

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