Computation of Interaural Time Difference in the Owl's Coincidence Detector Neurons

Both the mammalian and avian auditory systems localize sound sources by computing the interaural time difference (ITD) with submillisecond accuracy. The neural circuits for this computation in birds consist of axonal delay lines and coincidence detector neurons. Here, we report the first in vivo intracellular recordings from coincidence detectors in the nucleus laminaris of barn owls. Binaural tonal stimuli induced sustained depolarizations (DC) and oscillating potentials whose waveforms reflected the stimulus. The amplitude of this sound analog potential (SAP) varied with ITD, whereas DC potentials did not. The amplitude of the SAP was correlated with firing rate in a linear fashion. Spike shape, synaptic noise, the amplitude of SAP, and responsiveness to current pulses differed between cells at different frequencies, suggesting an optimization strategy for sensing sound signals in neurons tuned to different frequencies

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Ramos Cells Using Bio-phantoms

The roles of cell density, extracellular space, intracellular factors, and apoptosis induced by the molecularly targeted drug rituximab on the apparent diffusion coefficient (ADC) values were investigated using bio-phantoms. In these bio-phantoms, Ramos cells (a human Burkittｾs lymphoma cell line) were encapsulated in gellan gum. The ADC values decreased linearly with the increase in cell density, and declined steeply when the extracellular space became less than 4 μm. The analysis of ADC values after destruction of the cellular membrane by sonication indicated that approximately 65% of the ADC values of normal cells originate from the cell structures made of membranes and that the remaining 35% originate from intracellular components. Microparticles, defined as particles smaller than the normal cells, increased in number after rituximab treatments, migrated to the extracellular space and significantly decreased the ADC values of bio-phantoms during apoptosis. An in vitro study using bio-phantoms was conducted to quantitatively clarify the roles of cellular factors and of extracellular space in determining the ADC values yielded by tumor cells and the mechanism by which apoptosis changes those values

In Vitro Assessment of Factors Affecting the Apparent Diffusion Coefficient of Jurkat Cells Using Bio-phantoms

It is well known that many tumor tissues show lower apparent diffusion coefficient (ADC) values, and that several factors are involved in the reduction of ADC values. The aim of this study was to clarify how much each factor contributes to decreases in ADC values. We investigate the roles of cell density, extracellular space, intracellular factors, apoptosis and necrosis in ADC values using bio-phantoms. The ADC values of bio-phantoms, in which Jurkat cells were encapsulated by gellan gum, were measured by a 1.5-Tesla magnetic resonance imaging device with constant diffusion time of 30sec. Heating at 42℃ was used to induce apoptosis while heating at 48℃ was used to induce necrosis. Cell death after heating was evaluated by flow cytometric analysis and electron microscopy. The ADC values of bio-phantoms including non-heated cells decreased linearly with increases in cell density, and showed a steep decline when the distance between cells became less than 3μm. The analysis of ADC values of cells after destruction of cellular structures by sonication suggested that approximately two-thirds of the ADC values of cells originate from their cellular structures. The ADC values of bio-phantoms including necrotic cells increased while those including apoptotic cells decreased. This study quantitatively clarified the role of the cellular factors and the extracellular space in determining the ADC values produced by tumor cells. The intermediate diffusion time of 30msec might be optimal to distinguish between apoptosis and necrosis

Passive Soma Facilitates Submillisecond Coincidence Detection in the Owl's Auditory System

Neurons of the avian nucleus laminaris (NL) compute the interaural time difference (ITD) by detecting coincident arrivals of binaural signals with submillisecond accuracy. The cellular mechanisms for this temporal precision have long been studied theoretically and experimentally. The myelinated axon initial segment in the owl's NL neuron and small somatic spikes observed in auditory coincidence detector neurons of various animals suggest that spikes in the NL neuron are generated at the first node of Ranvier and that the soma passively receives back-propagating spikes. To investigate the significance of the “passive soma” structure, we constructed a two-compartment NL neuron model, consisting of a cell body and a first node, and systematically changed the excitability of each compartment. Here, we show that a neuron with a less active soma achieves higher ITD sensitivity and higher noise tolerance with lower energy costs. We also investigate the biophysical mechanism of the computational advantage of the “passive soma” structure by performing sub- and suprathreshold analyses. Setting a spike initiation site with high sodium conductance, not in the large soma but in the small node, serves to amplify high-frequency input signals and to reduce the impact and the energy cost of spike generation. Our results indicate that the owl's NL neuron uses a “passive soma” design for computational and metabolic reasons