Gamma Synchronization Influences Map Formation Time in a Topological Model of Spatial Learning.

The mammalian hippocampus plays a crucial role in producing a cognitive map of space-an internalized representation of the animal's environment. We have previously shown that it is possible to model this map formation using a topological framework, in which information about the environment is transmitted through the temporal organization of neuronal spiking activity, particularly those occasions in which the firing of different place cells overlaps. In this paper, we discuss how gamma rhythm, one of the main components of the extracellular electrical field potential affects the efficiency of place cell map formation. Using methods of algebraic topology and the maximal entropy principle, we demonstrate that gamma modulation synchronizes the spiking of dynamical cell assemblies, which enables learning a spatial map at faster timescales.

The effects of theta precession on spatial learning and simplicial complex dynamics in a topological model of the hippocampal spatial map.

Learning arises through the activity of large ensembles of cells, yet most of the data neuroscientists accumulate is at the level of individual neurons; we need models that can bridge this gap. We have taken spatial learning as our starting point, computationally modeling the activity of place cells using methods derived from algebraic topology, especially persistent homology. We previously showed that ensembles of hundreds of place cells could accurately encode topological information about different environments ("learn" the space) within certain values of place cell firing rate, place field size, and cell population; we called this parameter space the learning region. Here we advance the model both technically and conceptually. To make the model more physiological, we explored the effects of theta precession on spatial learning in our virtual ensembles. Theta precession, which is believed to influence learning and memory, did in fact enhance learning in our model, increasing both speed and the size of the learning region. Interestingly, theta precession also increased the number of spurious loops during simplicial complex formation. We next explored how downstream readout neurons might define co-firing by grouping together cells within different windows of time and thereby capturing different degrees of temporal overlap between spike trains. Our model's optimum coactivity window correlates well with experimental data, ranging from ∼150-200 msec. We further studied the relationship between learning time, window width, and theta precession. Our results validate our topological model for spatial learning and open new avenues for connecting data at the level of individual neurons to behavioral outcomes at the neuronal ensemble level. Finally, we analyzed the dynamics of simplicial complex formation and loop transience to propose that the simplicial complex provides a useful working description of the spatial learning process.

Impact of a pharmacist-implemented anemia management in outpatients with end-stage renal disease in Japan.

Given the absence of standard guidelines for use of recombinant human erythropoietin in patients with end-stage renal disease in Japan, in the present study, pharmacists actively managed the erythropoietin therapy, and the therapeutic and pharmacoeconomic outcome was evaluated. We compiled in-hospital guidelines for proper use of erythropoietin for outpatients with renal anemia under hemodialysis, and made recommendations, particularly about changes in the doses of erythropoietin and administration of iron preparations, to physicians. The clinical test values and the dosages of erythropoietin were monitored for 9 months and analyzed. As results of our participation, the number of renal anemia patients with over 30% of the hematocrit value as a therapeutic target increased from 7 to 32 among 41 patients. Twenty three of the 41 patients could decrease the dose of erythropoietin, and 5 patients could cease receiving the drug. Monthly total units of erythropoietin used for the 41 patients could also be decreased from 915000 units to 642000 units, resulting in considerable improvement of cost performance. Thus, active participation of pharmacists in management of renal anemia had great therapeutic and pharmacoecomic impact in Japan, as in North America.