1. Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus
- Author
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Lutzu, Stefano, Alviña, Karina, Puente, Nagore, Grandes, Pedro, and Castillo, Pablo E.
- Subjects
Cellular and Molecular Neuroscience ,synaptic plasticity ,two-photon laser scanning microscopy ,calcium signal ,CA3 ,mossy cell ,dentate gyrus - Abstract
Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity. We found that postsynaptic calcium transients (CaTs) in response to hippocampal MF stimulation were significantly larger during the induction of NMDAR-LTP compared to NMDAR-LTD at the MF-to-CA3 pyramidal cell (MF-CA3) synapse. This difference was abolished by pharmacological blockade of mGluR5 and was significantly reduced by depletion of intracellular calcium stores, whereas blocking mGluR1 had no effect on these CaTs. In addition, we discovered that MF to hilar mossy cell (MF-MC) synapses, which share several structural and functional commonalities with MF-CA3 synapses, also undergoes NMDAR plasticity. To our surprise, however, we found that the postsynaptic distribution of I-mGluR subtypes at these two synapses differ, and the same induction protocol that induces NMDAR-LTD at MF-CA3 synapses, only triggered NMDAR-LTP at MF-MC synapses, despite a comparable calcium dynamics. Thus, postsynaptic calcium dynamics alone cannot predict the sign of NMDAR plasticity, indicating that both postsynaptic calcium rise and the relative contribution of I-mGluR subtypes likely determine the learning rules of NMDAR plasticity. This research was supported by the National Institutes of Health (NIH), R01-NS113600, R01-MH125772, R01-MH116673, and R01-MH081935 to PC, and by The Basque Government (IT1620-22), Red de Investigación en Atención Primaria de Adicciones (RIAPAd), Instituto de Salud Carlos III (RD21/0009/0006), and Ministry of Science and Innovation (PID2019-107548RB-I00) to PG.
- Published
- 2023