Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse.

Neuronal nitric oxide synthase (nNOS) is broadly expressed in the brain and associated with synaptic plasticity through NMDAR-mediated calcium influx. However, its physiological activation and the mechanisms by which nitric oxide (NO) influences synaptic transmission have proved elusive. Here, we exploit the unique input-specificity of the calyx of Held to characterize NO modulation at this glutamatergic synapse in the auditory pathway.

Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons.

The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K(+) current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of approximately 37 nS; it is half-activated at -9.

Kv4 (A-type) potassium currents in the mouse medial nucleus of the trapezoid body.

Principal neurones of the mouse medial nucleus of the trapezoid body (MNTB) possess multiple voltage-gated potassium currents, including a transient outward current (or A-current), which is characterized here. The A-current exhibited rapid voltage-dependent inactivation and was half inactivated at resting membrane potentials. Following a hyperpolarizing pre-pulse to remove inactivation, the peak transient current was 1.

Listeners' sensitivity to "onset/offset" and "ongoing" interaural delays in high-frequency, sinusoidally amplitude-modulated tones.

The relative potency of onset/offset and envelope-based ongoing interaural time delays (ITDs) was assessed using high-frequency stimuli. A two-cue, two-alternative, forced-choice adaptive task was employed to measure threshold ITDs with 100% sinusoidally amplitude-modulated tones centered at 4 kHz. Modulation rates of 125, 250, and 350 Hz were tested with durations of 32, 90, or 240 ms.

Neural sensitivity to interaural envelope delays in the inferior colliculus of the guinea pig.

Interaural time differences (ITDs) are important cues for mammalian sound localization. At high frequencies, sensitivity to ITDs, which are conveyed only by the envelope of the waveforms, has been shown to be poorer than sensitivity to ITDs at low frequencies, which are conveyed primarily by the fine structure of the waveforms. Recently, human psychophysical experiments have demonstrated that sensitivity to envelope-based ITDs in high-frequency transposed tones can be equivalent to low-frequency fine-structure-based ITD sensitivity.

Prediction of in vitro intrinsic clearance from hepatocytes: comparison of suspensions and monolayer cultures.

Due to the time-dependent loss of cytochrome P450 (P450)-mediated metabolism in freshly isolated hepatocytes, several types of culture systems have been developed to extend their lifespan. The aim of this study was to evaluate the ability of monolayer cultures of rat hepatocytes to determine the in vitro CL(int) compared with suspensions of freshly isolated hepatocytes. Seven compounds were incubated in rat hepatocyte suspensions and monolayer cultures, and in vitro CL(int) was obtained via metabolite formation (12 pathways) or substrate depletion approaches.

Comparison of fresh and cryopreserved rat hepatocyte suspensions for the prediction of in vitro intrinsic clearance.

Freshly isolated hepatocytes are currently regarded as the most superior in vitro model for use in prediction studies, in particular to provide estimates of in vivo intrinsic clearance (CL(int)). However, due to their loss of viability within 4 h and a decrease in cytochrome P450-dependent metabolism upon culture, newer cellular models are being developed. Cryopreserved hepatocytes have several potential advantages, but to date evaluation of the utility of this model for estimating in vitro CL(int) has been limited to the substrate depletion approach.