Differential sensitivity of brainstem vs cortical astrocytes to changes in pH reveals functional regional specialization of astroglia

Astrocytes might function as brain interoceptors capable of detecting different (chemo)sensory modalities and transmitting sensory information to the relevant neural networks controlling vital functions. For example, astrocytes which reside near the ventral surface of the brainstem (central respiratory chemosensitive area) respond to physiological decreases in pH with vigorous elevations in intracellular Ca(2+) and release of ATP. ATP transmits astroglial excitation to the brainstem respiratory network and contributes to adaptive changes in lung ventilation. Here we show that in terms of pH-sensitivity ventral brainstem astrocytes are clearly distinct from astrocytes residing in the cerebral cortex. We monitored vesicular fusion in cultured rat brainstem astrocytes using total internal reflection fluorescence microscopy and found that approximately 35% of them respond to acidification with an increased rate of exocytosis of ATP-containing vesicular compartments. These fusion events require intracellular Ca(2+) signaling and are independent of autocrine ATP actions. In contrast, the rate of vesicular fusion in cultured cortical astrocytes is not affected by changes in pH. Compared to cortical astrocytes, ventral brainstem astrocytes display higher levels of expression of genes encoding proteins associated with ATP vesicular transport and fusion, including vesicle-associated membrane protein-3 and vesicular nucleotide transporter. These results suggest that astrocytes residing in different parts of the rat brain are functionally specialized. In contrast to cortical astrocytes, astrocytes of the brainstem chemosensitive area(s) possess signaling properties which are functionally relevant – they are able to sense changes in pH and respond to acidification with enhanced vesicular release of ATP

Equivariant geometric K-homology for compact Lie group actions

Let G be a compact Lie-group, X a compact G-CW-complex. We define equivariant geometric K-homology groups K^G_*(X), using an obvious equivariant version of the (M,E,f)-picture of Baum-Douglas for K-homology. We define explicit natural transformations to and from equivariant K-homology defined via KK-theory (the "official" equivariant K-homology groups) and show that these are isomorphism.Comment: 25 pages. v2: some mistakes corrected, more detail added, Michael Walter as author added. To appear in Abhandlungen aus dem Mathematischen Seminar der Universit\"at Hambur

Equivariant Lefschetz maps for simplicial complexes and smooth manifolds

Let X be a locally compact space with a continuous proper action of a locally compact group G. Assuming that X satisfies a certain kind of duality in equivariant bivariant Kasparov theory, we can enrich the classical construction of Lefschetz numbers to equivariant K-homology classes. We compute the Lefschetz invariants for self-maps of finite-dimensional simplicial complexes and of self-maps of smooth manifolds. The resulting invariants are independent of the extra structure used to compute them. Since smooth manifolds can be triangulated, we get two formulas for the same Lefschetz invariant in these cases. The resulting identity is closely related to the equivariant Lefschetz Fixed Point Theorem of Luck and Rosenberg.Comment: Minor revisions, affecting some theorem number

Operator *-correspondences in analysis and geometry

An operator *-algebra is a non-selfadjoint operator algebra with completely isometric involution. We show that any operator *-algebra admits a faithful representation on a Hilbert space in such a way that the involution coincides with the operator adjoint up to conjugation by a symmetry. We introduce operator *-correspondences as a general class of inner product modules over operator *-algebras and prove a similar representation theorem for them. From this we derive the existence of linking operator *-algebras for operator *-correspondences. We illustrate the relevance of this class of inner product modules by providing numerous examples arising from noncommutative geometry.Comment: 31 pages. This work originated from the MFO workshop "Operator spaces and noncommutative geometry in interaction

Expression of Microbial Enzymes in Mammalian Astrocytes to Modulate Lactate Release

Astrocytes support and modulate neuronal activity through the release of L-lactate. The suggested roles of astrocytic lactate in the brain encompass an expanding range of vital functions, including central control of respiration and cardiovascular performance, learning, memory, executive behaviour and regulation of mood. Studying the effects of astrocytic lactate requires tools that limit the release of lactate selectively from astrocytes. Here, we report the validation in vitro of novel molecular constructs derived from enzymes originally found in bacteria, that when expressed in astrocytes, interfere with lactate handling. When lactate 2-monooxygenase derived from M. smegmatis was specifically expressed in astrocytes, it reduced intracellular lactate pools as well as lactate release upon stimulation. D-lactate dehydrogenase derived from L. bulgaricus diverts pyruvate towards D-lactate production and release by astrocytes, which may affect signalling properties of lactate in the brain. Together with lactate oxidase, which we have previously described, this set of transgenic tools can be employed to better understand astrocytic lactate release and its role in the regulation of neuronal activity in different behavioural contexts

Uniformization and an Index Theorem for Elliptic Operators Associated with Diffeomorphisms of a Manifold

We consider the index problem for a wide class of nonlocal elliptic operators on a smooth closed manifold, namely differential operators with shifts induced by the action of an isometric diffeomorphism. The key to the solution is the method of uniformization: We assign to the nonlocal problem a pseudodifferential operator with the same index, acting in sections of an infinite-dimensional vector bundle on a compact manifold. We then determine the index in terms of topological invariants of the symbol, using the Atiyah-Singer index theorem.Comment: 16 pages, no figure

A Short Survey of Noncommutative Geometry

We give a survey of selected topics in noncommutative geometry, with some emphasis on those directly related to physics, including our recent work with Dirk Kreimer on renormalization and the Riemann-Hilbert problem. We discuss at length two issues. The first is the relevance of the paradigm of geometric space, based on spectral considerations, which is central in the theory. As a simple illustration of the spectral formulation of geometry in the ordinary commutative case, we give a polynomial equation for geometries on the four dimensional sphere with fixed volume. The equation involves an idempotent e, playing the role of the instanton, and the Dirac operator D. It expresses the gamma five matrix as the pairing between the operator theoretic chern characters of e and D. It is of degree five in the idempotent and four in the Dirac operator which only appears through its commutant with the idempotent. It determines both the sphere and all its metrics with fixed volume form. We also show using the noncommutative analogue of the Polyakov action, how to obtain the noncommutative metric (in spectral form) on the noncommutative tori from the formal naive metric. We conclude on some questions related to string theory.Comment: Invited lecture for JMP 2000, 45

Fluxes, Brane Charges and Chern Morphisms of Hyperbolic Geometry

The purpose of this paper is to provide the reader with a collection of results which can be found in the mathematical literature and to apply them to hyperbolic spaces that may have a role in physical theories. Specifically we apply K-theory methods for the calculation of brane charges and RR-fields on hyperbolic spaces (and orbifolds thereof). It is known that by tensoring K-groups with the rationals, K-theory can be mapped to rational cohomology by means of the Chern character isomorphisms. The Chern character allows one to relate the analytic Dirac index with a topological index, which can be expressed in terms of cohomological characteristic classes. We obtain explicit formulas for Chern character, spectral invariants, and the index of a twisted Dirac operator associated with real hyperbolic spaces. Some notes for a bivariant version of topological K-theory (KK-theory) with its connection to the index of the twisted Dirac operator and twisted cohomology of hyperbolic spaces are given. Finally we concentrate on lower K-groups useful for description of torsion charges.Comment: 26 pages, no figures, LATEX. To appear in the Classical and Quantum Gravit

Homology and K--Theory Methods for Classes of Branes Wrapping Nontrivial Cycles

We apply some methods of homology and K-theory to special classes of branes wrapping homologically nontrivial cycles. We treat the classification of four-geometries in terms of compact stabilizers (by analogy with Thurston's classification of three-geometries) and derive the K-amenability of Lie groups associated with locally symmetric spaces listed in this case. More complicated examples of T-duality and topology change from fluxes are also considered. We analyse D-branes and fluxes in type II string theory on ${\mathbb C}P^3\times \Sigma_g \times {\mathbb T}^2$ with torsion $H-$flux and demonstrate in details the conjectured T-duality to ${\mathbb R}P^7\times X^3$ with no flux. In the simple case of $X^3 = {\mathbb T}^3$, T-dualizing the circles reduces to duality between ${\mathbb C}P^3\times {\mathbb T}^2 \times {\mathbb T}^2$ with $H-$flux and ${\mathbb R}P^7\times {\mathbb T}^3$ with no flux.Comment: 27 pages, tex file, no figure