Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep

The relationship between orexin/hypocretin and rapid eye movement (REM) sleep remains elusive. Here, we find that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus (SLD) and exhibit REM sleep-related activation. In SLD, orexin directly excites orexin receptor-positive neurons (occupying ~3/4 of total-population) and increases gap junction conductance among neurons. Their interaction spreads the orexin-elicited partial-excitation to activate SLD network globally. Besides, the activated SLD network exhibits increased probability of synchronized firings. This synchronized excitation promotes the correspondence between SLD and its downstream target to enhance SLD output. Using optogenetics and fiber-photometry, we consequently find that orexin-enhanced SLD output prolongs REM sleep episodes through consolidating brain state activation/muscle tone inhibition. After chemogenetic silencing of SLD orexin signaling, a ~17% reduction of REM sleep amounts and disruptions of REM sleep muscle atonia are observed. These findings reveal a stabilization role of orexin in REM sleep.

Gap Junction Dynamics Induces Localized Conductance Bistability in Cardiac Tissue

Connexins are specialized ionic channels that control the action potential propagation between cardiac myocytes. In this paper, we study the connexin dynamics in a one-dimensional model of cardiac tissue. We show that the connexin dynamics may lead to a spatial organization of the gap junction conductance. In the numerical simulations presented in this paper we have found two different regimes for the spatial organization of the conductances: (a) a spatially uniform conductance; (b) a spatially complex pattern of local values of high and low conductances. In addition, we have observed that, locally, the two final states are limit cycles with a period equal to the period associated with the external excitation of the tissue strand. The conductance dispersion usually takes place on a very large time scale, i.e. thousands of heart beats, and on a very short spatial scale. Due to its simplicity, the one-dimensional setting allows a detailed study of the emerging structure and in particular very long simulations. We have studied the transition between the two aforementioned states as a function of the gap junction conductance characteristics. Furthermore, we have studied the effect of initially added noises on the outcome of the system. Finally, using spatial autocorrelation functions we have characterized the spatial dispersion in conductance values.

Opposing modulation of Cx26 gap junctions and hemichannels by CO2

SummaryCx26 hemichannels open in response to moderate elevations of CO2 (PCO2 55 mmHg) via a carbamylation reaction that depends on residues K125 and R104. Here we investigate the action of CO2 on Cx26 gap junctions. Using a dye transfer assay, we found that an elevated PCO2 of 55 mmHg greatly delayed the permeation of a fluorescent glucose analogue (NBDG) between HeLa cells coupled by Cx26 gap junctions. However, the mutations K125R or R104A abolished this effect of CO2. Whole cell recordings demonstrated that elevated CO2 reduced the Cx26 gap junction conductance (median reduction 5.6 nS, 95% confidence interval, 3.2 to 11.9 nS) but had no effect on Cx26K125R or Cx31 gap junctions. CO2 can cause intracellular acidification, but using 30 mM propionate we found that acidification in the absence of a change in PCO2 caused a median reduction in the gap junction conductance of 5.3 nS (2.8 to 8.3 nS). This effect of propionate was unaffected by the K125R mutation (median reduction 7.7 nS, 4.1 to 11.0 nS). pH-dependent and CO2-dependent closure of the gap junction are thus mechanistically independent. Mutations of Cx26 associated with the Keratitis Ichthyosis Deafness syndrome (N14K, A40V and A88V) also abolished the CO2-dependent gap junction closure. Elastic network modelling suggests that the lowest entropy state when CO2 is bound, is the closed configuration for the gap junction but the open state for the hemichannel. The opposing actions of CO2 on Cx26 gap junctions and hemichannels thus depend on the same residues and presumed carbamylation reaction.

Topological quantum computation based on chiral Majorana fermions

The chiral Majorana fermion is a massless self-conjugate fermion which can arise as the edge state of certain 2D topological matters. It has been theoretically predicted and experimentally observed in a hybrid device of a quantum anomalous Hall insulator and a conventional superconductor. Its closely related cousin, the Majorana zero mode in the bulk of the corresponding topological matter, is known to be applicable in topological quantum computations. Here we show that the propagation of chiral Majorana fermions leads to the same unitary transformation as that in the braiding of Majorana zero modes and propose a platform to perform quantum computation with chiral Majorana fermions. A Corbino ring junction of the hybrid device can use quantum coherent chiral Majorana fermions to implement the Hadamard gate and the phase gate, and the junction conductance yields a natural readout for the qubit state.