Presynaptic NMDARs and astrocytes ally to control circuit-specific information flow
Isabel Pérez-Otaño and Antonio Rodríguez-Moreno
PNAS July 2, 2019 116 (27) 13166-13168; first published June 14, 2019 https://doi.org/10.1073/pnas.1908293116
Isabel Pérez-Otaño
aInstituto de Neurociencias, Consejo Superior de Investigaciones Científicas y Universidad Miguel Hernández, 03550 San Juan de Alicante, Spain;
Antonio Rodríguez-Moreno
bLaboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, ES-41013 Seville, Spain
For correspondence: arodmor@upo.es
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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 …
↵1To whom correspondence may be addressed. Email: arodmor{at}upo.es.
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Isabel Pérez-Otaño, Antonio Rodríguez-Moreno
Proceedings of the National Academy of Sciences Jul 2019, 116 (27) 13166-13168; DOI: 10.1073/pnas.1908293116
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