Hydrolysis rate constants of ATP determined in situ at elevated temperatures.

Life can be found even in extreme environments, e.g., near black smokers on the ocean floor at temperatures up to ca. 120 °C and hydrostatic pressures of 40 MPa. To maintain vital reactions under these hostile conditions, extremophiles are interacting with the surrounding geochemical system. In this context, the stabilities of the essential energy-storing adenosine triphosphate (ATP) and adenosine diphosphate (ADP) are of fundamental importance because reactions involving adenosine phosphates constrain the conditions at which carbon-based life can exist and might be also crucial information for the search of extra-terrestrial life. Adenosine phosphates react by non-enzymatic hydrolysis, which is kinetically enhanced at high temperatures. If these abiotic hydrolysis processes are too rapid, they will most likely prevent metabolisms from relying on ATP. Here, we report on an approach used in experimental geochemistry, i.e., in situ Raman spectroscopic analyses of a fluid phase at high temperature using a hydrothermal diamond anvil cell. This combination allowed the investigation of the hydrolysis of Adenosine Tri-Phosphate (ATP) in aqueous solution at pH 3 and 7 and at temperatures of 80, 100 and 120 °C, extending the so far measured temperature range substantially. We observed Arrhenian behaviour over this temperature interval. The rate constants at 120 °C were 4.34 × 10-3 s-1 at pH 3 and 2.91 × 10-3 s-1 at pH 7. This corresponds to ATP half-lives of a few minutes. These high decomposition rates of ATP suggest that organisms must have developed a mechanism to counteract this fast reaction at high temperatures to maintain the vital processes.

Critical role for cochlear hair cell BK channels for coding the temporal structure and dynamic range of auditory information for central auditory processing.

Large conductance, voltage- and Ca(2+)-activated K(+) (BK) channels in inner hair cells (IHCs) of the cochlea are essential for hearing. However, germline deletion of BKα, the pore-forming subunit KCNMA1 of the BK channel, surprisingly did not affect hearing thresholds in the first postnatal weeks, even though altered IHC membrane time constants, decreased IHC receptor potential alternating current/direct current ratio, and impaired spike timing of auditory fibers were reported in these mice. To investigate the role of IHC BK channels for central auditory processing, we generated a conditional mouse model with hair cell-specific deletion of BKα from postnatal day 10 onward. This had an unexpected effect on temporal coding in the central auditory system: neuronal single and multiunit responses in the inferior colliculus showed higher excitability and greater precision of temporal coding that may be linked to the improved discrimination of temporally modulated sounds observed in behavioral training. The higher precision of temporal coding, however, was restricted to slower modulations of sound and reduced stimulus-driven activity. This suggests a diminished dynamic range of stimulus coding that is expected to impair signal detection in noise. Thus, BK channels in IHCs are crucial for central coding of the temporal fine structure of sound and for detection of signals in a noisy environment.

Long-range effects of GABAergic inhibition in gerbil primary auditory cortex.

Throughout the literature, the effects of iontophoretically applied neurotransmitter agonists or antagonists on the local activity of neurons are typically studied at the site of drug application. Recently, we have demonstrated long-range inhibitory interactions within the primary auditory cortex (AI) that are effective in complex acoustic situations. To further characterize this long-range functional connectivity, we here report the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the GABA(A) antagonist gabazine (SR 95531) on neuronal activity as a function of distance from the application site reaching beyond the diffusion radius of the applied drug. Neuronal responses to pure tone stimulation were simultaneously recorded at the application site and four additional sites, at distances between 300 and 1350 microm from the application site. We found that whereas application of GABA during best frequency (BF) stimulation in general led to a decrease, and gabazine to an increase, in neuronal activity at the application site, a considerable number of units at remote recording sites showed effects opposite to these local, drug-induced effects. These effects were seen both in spiking activity and in amplitudes of local field potentials. At all locations, the effects varied as a function of pure tone stimulation frequency, pointing to a Mexican-hat-like input function resulting from thalamic inputs to the BF region of the cortical neurons and intracortical interconnections projecting to off-BF regions of the neurons. These data demonstrate the existence of long-range, inhibitory interactions within the gerbil AI, realized either by long-range inhibitory projections or by long-range excitatory projections to local inhibitory interneurons.

Improvement of auditory discrimination learning by Ginkgo biloba extract EGb 761.

The effect of oral application of Ginkgo biloba extract EGb 761 on auditory discrimination learning in Mongolian gerbils was investigated using discrimination tasks with three different degrees of difficulty and two protocols for administration starting 2 weeks prior to or at the beginning of training. In comparison to placebo-treated controls we observed significant improvement of learning performance in EGb 761 treated gerbils in discrimination tasks of all degrees of difficulty, from the easiest to the most demanding. EGb 761 has been reported to increase the extracellular concentration of dopamine in prefrontal cortex of rats which plays a major role in the type of discrimination learning used in the present study. We, therefore, suppose that EGb 761 improves discrimination learning through its effect on the dopaminergic system.

Auditory cortical contrast enhancing by global winner-take-all inhibitory interactions.

Brains decompose the world into discrete objects of perception, thereby facing the problem of how to segregate and selectively address similar objects that are concurrently present in a scene. Theoretical models propose that this could be achieved by neuronal implementations of so-called winner-take-all algorithms where neuronal representations of objects or object features interact in a competitive manner. Here we present evidence for the existence of such a mechanism in an animal species. We present electrophysiological, neuropharmacological and neuroanatomical data which suggest a novel view of the role of GABA(A)-mediated inhibition in primary auditory cortex (AI), where intracortical GABA(A)-mediated inhibition operates on a global scale within a circular map of sound periodicity representation in AI, with functionally inhibitory projections of similar effect from any location throughout the whole map. These interactions could underlie the proposed competitive "winner-take-all" algorithm to support object segregation, e.g., segregation of different speakers in cocktail-party situations.

Differential effects of iontophoretic application of the GABAA-antagonists bicuculline and gabazine on tone-evoked local field potentials in primary auditory cortex: interaction with ketamine anesthesia.

gamma-Aminobutric acid (GABA) is one of the main inhibitory transmitters in the central nervous system. In a recent study we have demonstrated differential effects of two iontophoretically applied GABA(A)-blockers, bicuculline (BIC) and gabazine (SR 95531), on neuronal responses in primary auditory cortex (AI): Whereas the only effect of gabazine was to block GABA(A)-mediated inhibition, BIC application additionally induced dose-dependent side effects, probably on calcium-dependent potassium channels. Here we investigated the effects of the two drugs on pure tone-evoked local field potentials (LFPs) in AI. In contrast to spiking activity, which reflects neuronal output, LFP are believed to mainly reflect dendritic activity and therefore neuronal input. LFPs were recorded from the left AI of anaesthetized and unanaesthetized Mongolian gerbils before, during and after microiontophoretic application of BIC and gabazine using multi-barrel glass electrodes. After the application of both drugs, a significant increase of the amplitude of the N1 component of the LFP was observed in both anaesthetized and unanaesthetized animals, but this increase was significantly more pronounced after BIC than after gabazine application, a result which corresponds to the effects on neuronal discharge rate reported earlier. In contrast, the effects of BIC and gabazine on LFP duration (prolongation) and LFP spectral tuning (sharpening) were affected by ketamine anesthesia, an effect that was not seen in the spiking data. We conclude from the data presented that the main functional role of GABA(A)-mediated inhibition in auditory cortex is to (1) prevent over-excitation (seizures) of cortical networks and (2) to speed up cortical processing.