AUTHOR=Simonova Natalia A. , Volgushev Maxim A. , Malyshev Alexey Y. TITLE=Enhanced Non-Associative Long-Term Potentiation in Immature Granule Cells in the Dentate Gyrus of Adult Rats JOURNAL=Frontiers in Synaptic Neuroscience VOLUME=14 YEAR=2022 URL=https://www.frontiersin.org/journals/synaptic-neuroscience/articles/10.3389/fnsyn.2022.889947 DOI=10.3389/fnsyn.2022.889947 ISSN=1663-3563 ABSTRACT=

The dentate gyrus is one of the few sites of neurogenesis in the adult brain. Integration of new-generated granule cells into the hippocampal circuitry provides a substrate for structural plasticity, fundamental for normal function of adult hippocampus. However, mechanisms of synaptic plasticity that mediate integration of new-generated granule cells into the existing circuitry remain poorly understood. Especially mechanisms of plasticity at GABA-ergic synapses remain elusive. Here, we show that postsynaptic spiking without presynaptic activation can induce heterosynaptic, non-associative plasticity at GABA-ergic inputs to both immature and mature granule cells. In both immature and mature neurons, plastic changes were bidirectional and individual inputs could express long-term potentiation (LTP) or long-term depression (LTD), or do not change. However, properties of non-associative plasticity dramatically change with maturation of newly generated granule cells: while in immature cells there was a clear predominance of non-associative LTP and net potentiation across the inputs, in mature neurons, potentiation and depression were balanced with no net change on average. We conclude that GABA-ergic inputs to granule cells are plastic, and that the rules for induction of non-associative plasticity change with maturation. We propose that potentiation-biased non-associative plasticity of GABA-ergic transmission might help to counter-balance an increase of excitatory drive that is facilitated by enhanced LTP at glutamatergic synapses in maturating granule cells. Such mechanism might help to build a strong GABA-ergic input to surviving active new cells, necessary for normal function of mature granule cells, which operate under a tight inhibitory control and generate sparse spiking activity.