Synaptic integration of new neurons in the adult hippocampus
Although the central nervous system has an extremely poor capacity for repair, the discovery of neuronal stem cells in the adult mammalian brain undermined an old dogma in neurosciences and raised new hopes for the treatment of neurodegenerative diseases. Cell proliferation occurs throughout the whole adult central nervous system, but new neurons are only generated in two discrete areas of the brain: the subventricular zone, from which neurons migrate into the olfactory bulb and the dentate gyrus of the hippocampus.
In the hippocampus, the function of adult neurogenesis is still unclear, but an increasing body of evidence suggests it plays an important role in learning. Indeed long-term potentiation (LTP), a physiological mechanism of learning, can be more easily induced in newly generated granule cells than in mature neurons, and inhibiting cell proliferation reduces learning capacities.
In addition to their possible role in hippocampal-dependent learning, the regenerative potential of neural stem cells offers great hope for clinical applications. Indeed, several current clinical trials aim at curing neurodegenerative diseases by either grafting neural stem cells, or stimulating endogenous neurogenesis.
However, the regenerative potential of adult neurogenesis and of grafting procedures critically depends on whether and how new neurons integrate into the circuitry, which is currently unknown. A definitive answer to these questions and a precise understanding of the role of newly generated neurons can only be obtained by fine morphological analyses at the synaptic level.The aim of our laboratory is to understand how newborn neurons integrate in the hippocampus, at the synaptic level. For this, we use a combination of live-cell imaging, confocal and electron microscopy, and behavioral approaches.
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