Interactions Among Positions in the Third and Fourth Membrane-Associated Domains at the Intersubunit Interface of the N-Methyl-D-Aspartate Receptor Forming Sites of Alcohol Action

The N-methyl-d-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position in both subunits adjacent to one previously identified, GluN1(Gly-638) and GluN2A(Phe-636), can strongly regulate ethanol sensitivity. Significant interactions affecting ethanol inhibition and receptor deactivation were observed at four pairs of positions in GluN1/GluN2A: Gly-638/Met-823, Phe-639/Leu-824, Met-818/Phe-636, and Leu-819/Phe-637; the latter pair also interacted with respect to desensitization. Two interactions involved a position in M4 of both subunits, GluN1(Met-818) and GluN2A(Leu-824), that does not by itself alter ethanol sensitivity, whereas a previously identified ethanol-sensitive position, GluN2A(Ala-825), did not unequivocally interact with any other position tested. These results also indicate a shift by one position of the predicted alignment of the GluN1 M4 domain. These findings have allowed for the refinement of the NMDA receptor M domain structure, demonstrate that this region can influence apparent agonist affinity, and support the existence of four sites of alcohol action on the NMDA receptor, each consisting of five amino acids at the M3-M4 domain intersubunit interfaces

Two Adjacent Phenylalanines In the NMDA Receptor GluN2A Subunit M3 Domain Interactively Regulate Alcohol Sensitivity and Ion Channel Gating

The N-methyl-d-aspartate (NMDA) receptor is a key target of ethanol action in the central nervous system. Alcohol inhibition of NMDA receptor function involves small clusters of residues in the third and fourth membrane-associated (M) domains. Previous results from this laboratory have shown that two adjacent positions in the M3 domain, F636 and F637, can powerfully regulate alcohol sensitivity and ion channel gating. In this study, we report that these positions interact with one another in the regulation of both NMDA receptor gating and alcohol action. Using dual mutant cycle analysis, we detected interactions among various substitution mutants at these positions with respect to regulation of glutamate EC50, steady-state to peak current ratios (Iss:Ip), mean open time, and ethanol IC50. This interaction apparently involves a balancing of forces on the M3 helix, such that the disruption of function due to a substitution at one position can be reversed by a similar substitution at the other position. For example, tryptophan substitution at F636 or F637 increased or decreased channel mean open time, respectively, but tryptophan substitution at both positions did not alter open time. Interestingly, the effects of a number of mutations on receptor kinetics and ethanol sensitivity appeared to depend upon subtle structural differences, such as those between the isomeric amino acids leucine and isoleucine, as they could not be explained on the basis of sidechain molecular volume or hydrophilicity

Dark polariton-solitons in semiconductor microcavities

We report the existence, symmetry breaking and other instabilities of dark polariton-solitons in semiconductor microcavities operating in the strong coupling regime. These half-light half-matter solitons are potential candidates for applications in all-optical signal processing. Their excitation time and required pump powers are a few orders of magnitude less than those of their weakly coupled light-only counterparts.Comment: submitted to PR

Spin resonance induced by a mechanical rotation of a polariton condensate

We study theoretically the polarization dynamics in a ring-shape bosonic condensate of exciton-polaritons confined in a rotating trap. The interplay between the rotating potential and TE-TM splitting of polariton modes offers a tool of control over the spin state and the angular momentum of the condensate. Specific selection rules describing the coupling of pseudospin and angular momentum are formulated. The resonant coupling between states having linear and circular polarizations leads to the polarization beats. The effect may be seen as a polariton analogy to the electronic magnetic resonance in the presence of constant and rotating magnetic fields. Remarkably, spin beats are induced by a purely mechanical rotation of the condensate

Persistent polarization oscillations in ring-shape polariton condensates

We predict the limit cycle solution for a ring-shape bosonic condensate of exciton-polaritons confined in an optically induced rotating trap. The limit cycle manifests itself with polarization oscillations on a characteristic timescale of tens of picoseconds. The effect arises due to the interplay between orbital motion and the polarization degree of freedom. It is specific to spinor bosonic condensates and would be absent in a scalar case, where a bi-stability of stationary solutions would be observed instead. This work offers a tool of initialisation and control of qubits based on superpositions of polariton condensates characterised by different topologic charges

Kinematics of the Broad-line Region of 3C 273 from a Ten-year Reverberation Mapping Campaign

Despite many decades of study, the kinematics of the broad-line region of 3C~273 are still poorly understood. We report a new, high signal-to-noise, reverberation mapping campaign carried out from November 2008 to March 2018 that allows the determination of time lags between emission lines and the variable continuum with high precision. The time lag of variations in H$\beta$ relative to those of the 5100 Angstrom continuum is $146.8_{-12.1}^{+8.3}$ days in the rest frame, which agrees very well with the Paschen-$\alpha$ region measured by the GRAVITY at The Very Large Telescope Interferometer. The time lag of the H$\gamma$ emission line is found to be nearly the same as for H$\beta$. The lag of the Fe II emission is $322.0_{-57.9}^{+55.5}$ days, longer by a factor of $\sim$2 than that of the Balmer lines. The velocity-resolved lag measurements of the H$\beta$ line show a complex structure which can be possibly explained by a rotation-dominated disk with some inflowing radial velocity in the H$\beta$-emitting region. Taking the virial factor of $f_{\rm BLR} = 1.3$, we derive a BH mass of $M_{\bullet} = 4.1_{-0.4}^{+0.3} \times 10^8 M_{\odot}$ and an accretion rate of $9.3\,L_{\rm Edd}\,c^{-2}$ from the H$\beta$ line. The decomposition of its $HST$ images yields a host stellar mass of $M_* = 10^{11.3 \pm 0.7} M_\odot$, and a ratio of $M_{\bullet}/M_*\approx 2.0\times 10^{-3}$ in agreement with the Magorrian relation. In the near future, it is expected to compare the geometrically-thick BLR discovered by the GRAVITY in 3C 273 with its spatially-resolved torus in order to understand the potential connection between the BLR and the torus.Comment: 17 pages, 12 figures, 6 tables, accepted for publication in The Astrophysical Journa