Medial Superior Olivary Neurons Receive Surprisingly Few Excitatory and Inhibitory Inputs with Balanced Strength and Short-Term Dynamics

Neurons in the medial superior olive (MSO) process microsecond interaural time differences, the major cue for localizing low-frequency sounds, by comparing the relative arrival time of binaural, glutamatergic excitatory inputs. This coincidence detection mechanism is additionally shaped by highly specialized glycinergic inhibition. Traditionally, it is assumed that the binaural inputs are conveyed by many independent fibers, but such an anatomical arrangement may decrease temporal precision. Short-term depression on the other hand might enhance temporal fidelity during ongoing activity. For the first time we show that binaural coincidence detection in MSO neurons may require surprisingly few but strong inputs, challenging long-held assumptions about mammalian coincidence detection. This study exclusively uses adult gerbils for in vitro electrophysiology, single-cell electroporation and immunohistochemistry to characterize the size and short-term plasticity of inputs to the MSO. We find that the excitatory and inhibitory inputs to the MSO are well balanced both in strength and short-term dynamics, redefining this fastest of all mammalian coincidence detector circuits

NMDA Currents Modulate the Synaptic Input–Output Functions of Neurons in the Dorsal Nucleus of the Lateral Lemniscus in Mongolian Gerbils

Neurons in the dorsal nucleus of the lateral lemniscus (DNLL) receive excitatory and inhibitory inputs from the superior olivary complex (SOC) and convey GABAergic inhibition to the contralateral DNLL and the inferior colliculi. Unlike the fast glycinergic inhibition in the SOC, this GABAergic inhibition outlasts auditory stimulation by tens of milliseconds. Two mechanisms have been postulated to explain this persistent inhibition. One, an “integration-based” mechanism, suggests that postsynaptic excitatory integration in DNLL neurons generates prolonged activity, and the other favors the synaptic time course of the DNLL output itself. The feasibility of the integration-based mechanism was tested in vitro in DNLL neurons of Mongolian gerbils by quantifying the cellular excitability and synaptic input–output functions (IO-Fs). All neurons were sustained firing and generated a near monotonic IO-F on current injections. From synaptic stimulations, we estimate that activation of approximately five fibers, each on average liberating ∼18 vesicles, is sufficient to trigger a single postsynaptic action potential. A strong single pulse of afferent fiber stimulation triggered multiple postsynaptic action potentials. The steepness of the synaptic IO-F was dependent on the synaptic NMDA component. The synaptic NMDA receptor current defines the slope of the synaptic IO-F by enhancing the temporal and spatial EPSP summation. Blocking this NMDA-dependent amplification during postsynaptic integration of train stimulations resulted into a ∼20% reduction of the decay time course of the GABAergic inhibition. Thus, our data show that the NMDA-dependent amplification of the postsynaptic activity contributes to the GABAergic persistent inhibition generated by DNLL neurons

Probing the intracellular calcium sensitivity of transmitter release during synaptic facilitation

In nerve terminals, residual Ca2+ remaining from previous activity can cause facilitation of transmitter release by a mechanism that is still under debate. Here we show that the intracellular Ca2+ sensitivity of transmitter release at the calyx of Held is largely unchanged during facilitation, which leaves an increased microdomain Ca2+ signal as a possible mechanism for facilitation. We measured the Ca2+ dependencies of facilitation, as well as of transmitter release, to estimate the required increment in microdomain Ca2+. These measurements show that linear summation of residual and microdomain Ca2+ accounts for only 30% of the observed facilitation. However, a small degree of supra-linearity in the summation of intracellular Ca2+ signals, which might be caused by saturation of cytosolic Ca2+ buffer(s), is sufficient to explain facilitation at this CNS synapse

Applying EMSL Capabilities to Biogeochemistry and Environmental Research

The Environmental Molecular Sciences laboratory (EMSL) is a national scientific user facility operated by the Pacific Northwest National Laboratory (PNNL) for the U.S. Department of Energy's Office of Biological and Environmental Research. Located in Richland, Washington, EMSL offers researchers a comprehensive array of cutting-edge capabilities unmatched anywhere else in the world and access to the expertise of over 300 resident users--all at one location. EMSL's resources are available on a peer-reviewed proposal basis and are offered at no cost if research results are shared in the open literature. Researchers are encouraged to submit a proposal centered around one of EMSL's four Science Themes, which represent growing areas of research: (1) Geochemistry/Biogeochemistry and Subsurface Science; (2) Atmospheric Aerosol Chemistry; (3) Biological Interactions and Dynamics; and (4) Science of Interfacial Phenomena. To learn more about EMSL, visit www.emsl.pnl.gov

Recapitalizing EMSL: Meeting Future Science and Technology Challenges

EMSL, located in Richland, Washington, is a national scientific user facility operated for the U.S. Department of Energy (DOE) by the Pacific Northwest National Laboratory. The vision that directed the development of EMSL as a problem-solving environment for environmental molecular science has led to significant scientific progress in many areas ranging from subsurface science to atmospheric sciences, and from biochemistry to catalysis. Our scientific staff and users are recognized nationally and internationally for their significant contributions to solving challenging scientific problems. We have explored new scientific frontiers and organized a vibrant and diverse user community in support of our mission as a national scientific user facility that provides integrated experimental and computational resources in the environmental molecular sciences. Users from around the world - from academia to industry and national laboratories to international research organizations - use the resources of EMSL because of the quality of science that we enable

Thermodynamic Modeling of Hanford Waste Tank 241-AN-107

The high level waste storage double-shell tanks at the Hanford site are highly basic. The high basicity is a key factor in controlling the chemical behavior of different components of the waste and in influencing the corrosion rate of the carbon steel primary tanks. However, the introduction of atmospheric CO2 can act to reduce the pH of the tank wastes over time and possibly alter the corrosion rate of the carbon steel tanks. In order to at least partially address this issue for waste tank 241-AN-107, thermodynamic modeling calculations were performed to predict the changes in pH and carbonate concentration that could occur as CO2 is absorbed from the atmosphere. The calculations extended to complete equilibrium with the partial pressure of CO2 in the atmosphere (i.e. pCO2 = 10-3.5 atm). Simulations were performed for both the “upper” segments of tank 241-AN-107, which have been influenced by the introduction of high concentrations of NaOH to the supernatant, and for the “lower” segments where the salt cake/interstitial liquid have not been substantially altered by the introduction of base concentration

Inhibiting the inhibition

The precedence effect describes the phenomenon whereby echoes are spatially fused to the location of an initial sound by selectively suppressing the directional information of lagging sounds (echo suppression). Echo suppression is a prerequisite for faithful sound localization in natural environments but can break down depending on the behavioral context. To date, the neural mechanisms that suppress echo directional information without suppressing the perception of echoes themselves are not understood. We performed in vivo recordings in Mongolian gerbils of neurons of the dorsal nucleus of the lateral lemniscus (DNLL), a GABAergic brainstem nucleus that targets the auditory midbrain, and show that these DNLL neurons exhibit inhibition that persists tens of milliseconds beyond the stimulus offset, so-called persistent inhibition (PI). Using in vitro recordings, we demonstrate that PI stems from GABAergic projections from the opposite DNLL. Furthermore, these recordings show that PI is attributable to intrinsic features of this GABAergic innervation. Implementation of these physiological findings into a neuronal model of the auditory brainstem demonstrates that, on a circuit level, PI creates an enhancement of responsiveness to lagging sounds in auditory midbrain cells. Moreover, the model revealed that such response enhancement is a sufficient cue for an ideal observer to identify echoes and to exhibit echo suppression, which agrees closely with the percepts of human subjects

Chemical Speciation of Americium, Curium and Selected Tetravalent Actinides in High Level Waste

Large volumes of high-level waste (HLW) currently stored in tanks at DOE sites contain both sludges and supernatants. The sludges are composed of insoluble precipitates of actinides, radioactive fission products, and nonradioactive components. The supernatants are alkaline carbonate solutions, which can contain soluble actinides, fission products, metal ions, and high concentrations of major electrolytes including sodium hydroxide, nitrate, nitrite, phosphate, carbonate, aluminate, sulfate, and organic complexants. The organic complexants include several compounds that can form strong aqueous complexes with actinide species and fission products including ethylenediaminetetraacetic acid (EDTA), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (HEDTA), nitrilotriacetic acid (NTA), iminodiacetic acid (IDA), citrate, glycolate, gluconate, and degradation products, formate and oxalate

Glycinergic inhibition tunes coincidence detection in the auditory brainstem

Neurons in the medial superior olive (MSO) detect microsecond differences in the arrival time of sounds between the ears (interaural time differences or ITDs),a crucial binaural cue for sound localization. Synaptic inhibition has been implicated in tuning ITD sensitivity, but the cellular mechanisms underlying its influence on coincidence detection are debated. Here we determine the impact of inhibition on coincidence detection in adult Mongolian gerbil MSO brain slices by testing precise temporal integration of measured synaptic responses using conductance-clamp. We find that inhibition dynamically shifts the peak timing of excitation, depending on its relative arrival time, which in turn modulates the timing of best coincidence detection. Inhibitory control of coincidence detection timing is consistent with the diversity of ITD functions observed in vivo and is robust under physiologically relevant conditions. Our results provide strong evidence that temporal interactions between excitation and inhibition on microsecond timescales are critical for binaural processing