期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：27
页码：13166-13168
DOI：10.1073/pnas.1908293116
出版社：The National Academy of Sciences of the United States of America
摘要：The entorhinal cortex (EC) conveys spatial, limbic, and sensory information to the hippocampus, which performs critical brain functions, including learning and memory processes and spatial information coding. Axons from superficial [layer (L)2] EC neurons make excitatory synapses onto granule cells (GCs) of the hippocampal dentate gyrus (DG), which prepare the information for further processing in other hippocampal regions (1). Afferents from the lateral and medial perforant path (LPP and MPP, respectively) convey different aspects of information to the DG, with the former related more to sensory information, and the latter to spatial location and limbic signals related to attention and motivation. They also have distinct patterns of input, contacting the outer (LPP) or middle (MPP) third of the molecular layer of the DG, and exhibit different functional properties (1, 2). The mechanistic bases of these differences are unknown and represent a challenge to understand circuit-specific biological computations as well as susceptibility to pathological insults. In PNAS, Savtchouk et al. (3) identify presynaptic N -methyl-d-aspartate receptors (pre-NMDARs) as a source of the differences in information processing between MPP and LPP fibers. Previous work by the group (4) demonstrated that glutamate released by astrocytes enhances the strength of PP-GC synapses. The effect seemed to be mediated by pre-NMDARs, which increased the probability of transmitter release and contained the glutamate receptor subunit GluN2b. However, the work made no distinction between LPP and MPP contributions and left unsolved an apparent incongruence: GluN2b subunits confer high voltage-dependent Mg2+ block to NMDAR channels, but pre-NMDARs at PP-GC synapses could be activated without previous depolarization or in the absence of action potential firing in the axons. The current work (3) demonstrates that this is possible because of the additional presence in the receptor channel of the atypical GluN3a subunit, which largely relieves NMDAR.
