The Old & The New: A Tale of Hippocampal Neurogenesis
As we go through life, our brain has the amazing capacity to change and adapt to the body and the external environment. This is known as neuroplasticity, and an especially plastic part of the brain is the dentate gyrus (DG) of the hippocampus, responsible for important cognitive functions such as memory formation and certain affective behaviors. We have learned in recent years that neurogenesis is an important mechanism for adult DG plasticity, wherein new dentate granule cells (DGCs) are added to an existing neuronal workforce. Dr.Shaoyu Ge and his group at SUNY, Stonybrook have shed light on previously unknown key events during DGC neurogenesis utilizing nVistaᵀᴹ miniscope imaging in the hippocampus of freely moving mice.
In the journal Neuron, Shen et al. detail how newborn DGCs’ survival depends on the coupling of pre-existing DGCs to the hippocampal vasculature. With the elegant use of the nVista miniscope among other methods, the researchers were able to observe in real time as adult DGCs communicated with parvalbumin (PV)-containing hippocampal interneurons to initiate Nitric Oxide (NO) signaling, which in turn increased blood circulation to the proximal micro-vessel. This neurovascular coupling then activated the Insulin Growth factor-1 (IGF-1) pathway to promote survival of the newly born DGCs.
Phew, these adults have their work cut out for them! (#relatable, anyone??)
So the baby DGCs are now thriving. Living their best life. But then what? How do they integrate into their family, society, world aka the existing hippocampal neuronal circuitry?
In a second study in Nature Communications, Wang et al. examine the dynamics of newborn DGCs’ integration into the existing neural network. Using the same nVista miniscope method as before, the authors caught GFP-labeled newborn DGCs in action- migrating horizontally in a process termed ‘lateral dispersion’ and even teaming up with neighboring cells to migrate in ‘leapfrog’ fashion (Yes, the children’s game leapfrog. Yes, biology is awesome.). Further, these leapfrogging DGCs were found to electrically couple to one another through gap junctions, which when disrupted through the deletion of an important junction protein connexin 43, prevented migration of the cells. This in turn impaired successful integration of newborn DGCs into the neural circuit, which resulted in defects in neural network morphology over the developmental timeline.
If you have now turned into a real-life mind-blown emoji… honestly, same.
This body of work is the first to offer such deep insights into in vivo neurogenesis in the adult dentate gyrus and opens up so many new avenues for research in hippocampal circuit neuroscience!
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Thank you for reading!
Shen, J., Wang, D., Wang, X., Gupta, S., Ayloo, B., Wu, S., Prasad, P., Xiong, Q., Xia, J. and Ge, S. (2019). Neurovascular Coupling in the Dentate Gyrus Regulates Adult Hippocampal Neurogenesis. Neuron.
Wang, J., Shen, J., Kirschen, G., Gu, Y., Jessberger, S. and Ge, S. (2019). Lateral dispersion is required for circuit integration of newly generated dentate granule cells. Nature Communications, 10(1).