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Circuit-Specific Control Of The Medial Entorhinal Inputs To The Dentate Gyrus By Atypical Presynaptic Nmdars Activated By Astrocytes, Iaroslav Savtchouk, Maria Amalia Di Castro, Rugina Ali, Hiltrud Stubbe, Rafael Lujan, Andrea Volterra

Biomedical Sciences Faculty Research and Publications

Here, we investigated the properties of presynaptic N-methyl-D-aspartate receptors (pre-NMDARs) at corticohippocampal excitatory connections between perforant path (PP) afferents and dentate granule cells (GCs), a circuit involved in memory encoding and centrally affected in Alzheimer’s disease and temporal lobe epilepsy. These receptors were previously reported to increase PP release probability in response to gliotransmitters released from astrocytes. Their activation occurred even under conditions of elevated Mg²⁺ and lack of action potential firing in the axons, although how this could be accomplished was unclear. We now report that these pre-NMDARs contain the GluN3a subunit conferring them low Mg^{2+ …}