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Abstract
In adult dentate gyrus neurogenesis, the link between maturation of newborn neurons and their function, such as behavioral pattern separation, has remained puzzling. By analyzing a theoretical model, we show that the switch from excitation to inhibition of the GABAergic input onto maturing newborn cells is crucial for their proper functional integration. When the GABAergic input is excitatory, cooperativity drives the growth of synapses such that newborn cells become sensitive to stimuli similar to those that activate mature cells. When GABAergic input switches to inhibitory, competition pushes the configuration of synapses onto newborn cells toward stimuli that are different from previously stored ones. This enables the maturing newborn cells to code for concepts that are novel, yet similar to familiar ones. Our theory of newborn cell maturation explains both how adult-born dentate granule cells integrate into the preexisting network and why they promote separation of similar but not distinct patterns.
Highlights
In the adult mammalian brain, neurogenesis, the production of new neurons, is restricted to a few brain areas, such as the olfactory bulb and the dentate gyrus (Deng et al, 2010)
We model a small patch of cells within dentate gyrus as a recurrent network of 100 137 dentate granule cells (DGCs) and 25 GABAergic interneurons, omitting the Mossy cells for the sake of 138 simplicity (Figure 1b)
The modeled interneurons correspond to SST-INs from the hilar-perforant83 path-associated interneurons (HIPP) category, as they are the providers of feedback inhibition to DGCs through dendritic projections (Stefanelli et al, 2016; Yuan et al, 2017; Groisman et al, 2020) (Figure 1 - figure supplement 1)
Summary
In the adult mammalian brain, neurogenesis, the production of new neurons, is restricted to a few brain areas, such as the olfactory bulb and the dentate gyrus (Deng et al, 2010). Adult-born cells in dentate gyrus mostly develop into dentate granule 31 cells (DGCs), the main excitatory cells that project to area CA3 of hippocam pus (Deng et al, 2010). Many of them die before they fully mature (Dayer et al, 2003). Their survival is experience-dependent, and relies upon NMDA receptor activation (Tashiro et al, 2006). After 4 weeks of maturation adult-born DGCs have only weak connections to interneu rons, while at 7 weeks of age their activity causes indirect inhibition of mature 44 DGCs (Temprana et al, 2015)
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