Four-Types of IIT-Induced Group Integrity of Plecoglossus altivelis.

Integrated information theory (IIT) was initially proposed to describe human consciousness in terms of intrinsic-causal brain network structures. Particularly, IIT 3.0 targets the system's cause-effect structure from spatio-temporal grain and reveals the system's irreducibility. In a previous study, we tried to apply IIT 3.0 to an actual collective behaviour in Plecoglossus altivelis. We found that IIT 3.0 exhibits qualitative discontinuity between three and four schools of fish in terms of Φ value distributions. Other measures did not show similar characteristics. In this study, we followed up on our previous findings and introduced two new factors. First, we defined the global parameter settings to determine a different kind of group integrity. Second, we set several timescales (from Δ t = 5 / 120 to Δ t = 120 / 120 s). The results showed that we succeeded in classifying fish schools according to their group sizes and the degree of group integrity around the reaction time scale of the fish, despite the small group sizes. Compared with the short time scale, the interaction heterogeneity observed in the long time scale seems to diminish. Finally, we discuss one of the longstanding paradoxes in collective behaviour, known as the heap paradox, for which two tentative answers could be provided through our IIT 3.0 analysis.

Finding continuity and discontinuity in fish schools via integrated information theory.

Collective behaviours are known to be the result of diverse dynamics and are sometimes likened to living systems. Although many studies have revealed the dynamics of various collective behaviours, their main focus has been on the information processing performed by the collective, not on interactions within the collective. For example, the qualitative difference between three and four elements in a system has rarely been investigated. Tononi et al. proposed integrated information theory (IIT) to measure the degree of consciousness Φ. IIT postulates that the amount of information loss caused by the minimum information partition is equivalent to the degree of information integration in the system. This measure is not only useful for estimating the degree of consciousness but can also be applied to more general network systems. Here, we obtained two main results from the application of IIT (in particular, IIT 3.0) to the analysis of real fish schools (Plecoglossus altivelis). First, we observed that the discontinuity on 〈Φ(N)〉 distributions emerges for a school of four or more fish. This transition was not observed by measuring the mutual information or the sum of the transfer entropy. We also analysed the IIT on Boids simulations with respect to different coupling strengths; however, the results of the Boids model were found to be quite different from those of real fish. Second, we found a correlation between this discontinuity and the emergence of leadership. We discriminate leadership in this paper from its traditional meaning (e.g. defined by transfer entropy) because IIT-induced leadership refers not to group behaviour, as in other methods, but the degree of autonomy (i.e. group integrity). These results suggest that integrated information Φ can reveal the emergence of a new type of leadership which cannot be observed using other measures.

The Susceptibilities of Human Ether-à-Go-Go-Related Gene Channel with the G487R Mutation to Arrhythmogenic Factors.

The human ether-à-go-go-related gene (hERG) channel mediates the rapid delayed rectifier potassium current (IKr) responsible for shaping the repolarization phase of cardiac action potentials. hERG mutation may cause hERG channel malfunction, leading to long QT syndrome and other arrhythmic disorders. Elucidation of the genotype-phenotype relationships of individual hERG mutations is key to the development of treatment for such arrhythmic disorders. We previously identified hERG(G487R), a missense mutant with a glycine-to-arginine substitution at position 487. In the absence of arrhythmogenic factors, hERG(G487R) subunit-containing channels show normal surface expression and gating kinetics. However, it remains unknown whether the mutation exacerbates hERG channel malfunction induced by arrhythmogenic factors. Here we used a voltage-clamp technique to compare the effects of the major arrythmogenic factors on wild-type hERG [hERG(WT)] and hERG(G487R) channel currents (IhERG) in HEK-293T cells. The extent of IhERG blockade by the antiarrhythmic drug dofetilide or E4031 was not different between these channels. On the other hand, the extracellular K(+) concentration ([K(+)]ex)-dependent changes in the rates of recovery from inactivation and deactivation of IhERG were rather less obvious for hERG(G487R) channel than for hERG(WT) channel. These findings suggest that the inheritance of hERG(G487R) does not increase the risk of arrhythmic disorders induced by antiarrhythmic drugs or hypokalemia.

Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line.

Memantine is a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, and is an approved drug for the treatment of moderate-to-severe Alzheimer's disease. We identified a mouse strain with a naturally occurring mutation and an ataxic phenotype that presents with severe leg cramps. To investigate the phenotypes of these mutant mice, we screened several phenotype-modulating drugs and found that memantine (10 mg/kg) disrupted the sense of balance in the mutants. Moreover, the mutant mice showed an attenuated optokinetic response (OKR) and impaired OKR learning, which was also observed in wild-type mice treated with memantine. Microsatellite analyses indicated that the Grid2 gene-deletion is responsible for these phenotypes. Patch-clamp analysis showed a relatively small change in NMDA-dependent current in cultured granule cells from Grid2 gene-deleted mice, suggesting that GRID2 is important for correct NMDA receptor function. In general, NMDA receptors are activated after the activation of non-NMDA receptors, such as AMPA receptors, and AMPA receptor dysregulation also occurs in Grid2 mutant mice. Indeed, the AMPA treatment enhanced memantine susceptibility in wild-type mice, which was indicated by balance sense and OKR impairments. The present study explores a new role for GRID2 and highlights the adverse effects of memantine in different genetic backgrounds.