A coupled-line coupler comprising a microstrip line, edge-coupled to a negative-refractive-index line, exhibits co-directional phase but contra-directional Poynting vectors on the lines, leading to backward coupling. A key feature of this coupler is that it can support complex coupled modes. The resulting exponential field decay enables enhanced coupling with moderate line lengths and spacing. An example 3 dB device has been implemented and tested at 3 GHz.

N-methyl-D-aspartate receptors (NMDARs) are required to shape activity-dependent connections in the developing and adult brain. Impaired NMDAR signalling through genetic or environmental insults causes a constellation of neurodevelopmental disorders that manifest as intellectual disability, epilepsy, autism, or schizophrenia. It is not clear whether the developmental impacts of NMDAR dysfunction can be overcome by interventions in adulthood. This question is paramount for neurodevelopmental disorders arising from mutations that occur in the GRIN genes, which encode NMDAR subunits, and the broader set of mutations that disrupt NMDAR function. We developed a mouse model where a congenital loss-of-function allele of Grin1 can be restored to wild type by gene editing with Cre recombinase. Rescue of NMDARs in adult mice yields surprisingly robust improvements in cognitive functions, including those that are refractory to treatment with current medications. These results suggest that neurodevelopmental disorders arising from NMDAR deficiency can be effectively treated in adults.

Highlights:GluN1 inducible rescue mice allow recovery of functional NMDA receptors in a neurodevelopmental model of schizophrenia.Rescue in adolescent or adult mice achieves a similar level of functional recovery.Cortically-mediated behaviors show complete or near complete rescue, but subcortically-mediated behaviors show limited rescue.Higher-order brain function appears amenable to treatment in adulthood and surprisingly unencumbered by critical period.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/140343 doi: bioRxiv preprint first posted online May. 20, 2017; 2 SUMMARY NMDA receptors (NMDAR) are important in the formation of activity-dependent connections in the brain. In sensory pathways, NMDAR disruption during discrete developmental periods has enduring effects on wiring and function. Yet, it is not clear whether NMDAR-limited critical periods exist for higher-order circuits governing mood and cognition. This question is urgent for neurodevelopmental disorders, like schizophrenia, that have NMDAR hypofunction and treatment-resistant cognitive symptoms. As proof of concept, we developed a novel mouse model where developmental NMDAR deficits can be ameliorated by inducible Cre recombinase.Rescue of NMDARs in either adolescence or adulthood yields surprisingly strong improvements in higher-order behavior. Similar levels of behavioral plasticity are observed regardless of intervention age, with degree of plasticity dependent on the specific behavioral circuit. These results reveal higher-order brain function as amenable to treatment in adulthood and identify NMDAR as a key target for cognitive dysfunction.

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