On the role of the wideband inhibitor in the dorsal cochlear nucleus: a computational modeling study.

Principal cells (type IV units) in the dorsal cochlear nucleus (DCN) are uniquely sensitive to (are inhibited by) energy minima or notches in acoustic spectra, which provide cues to sound localization. The once accepted conceptual model of the DCN suggested that this sensitivity was shaped largely by inhibitory inputs from wideband inhibitors (WBIs), which received auditory nerve inputs over a wide frequency range and inhibited type IV units over a narrow frequency range. A computational model based on this wide-input narrow-output conceptual model was able to reproduce quantitatively type IV unit responses to notch-noise stimuli as a function of notch width. Recent physiological results have shown however that WBIs are unresponsive to notch-noise stimuli with wide notch widths and thus have narrower auditory nerve fiber input bandwidths than previously assumed. A computational model based on a narrow-input narrow-output model of the WBI was unable to account fully for the notch sensitivity of type IV units suggesting the need to add a new component to the DCN circuit. The goal of this study was to test whether making the output bandwidth of the WBIs wide while keeping their input bandwidth narrow could explain the responses of type IV units to notch-noise stimuli. Anatomical evidence supports this model configuration, and the results show that such a model can produce strong inhibition in type IV units for wide notches. The results thus suggest that WBIs, in narrow-input wide-output form, are sufficient to account for the notch sensitivity of DCN type IV units.

Monaural spectral processing differs between the lateral superior olive and the inferior colliculus: physiological evidence for an acoustic chiasm.

Evidence suggests that the lateral superior olive (LSO) initiates an excitatory pathway specialized to process interaural level differences (ILDs), the primary cues used by mammals to localize high-frequency sounds in the horizontal plane. Type I units in the central nucleus of the inferior colliculus (ICC) of decerebrate cats exhibit monaural and binaural response properties qualitatively similar to those of LSO units, and are thus supposed to be the midbrain component of the ILD pathway. Studies have shown, however, that the responses of ICC cells do not often reflect simply the output of any single source of excitatory inputs. The goal of this study was to compare directly the monaural, spectral response properties of LSO and type I units measured in unanesthetized decerebrate cats. Compared to LSO units, type I units have narrower V-shaped excitatory tuning curves, higher spontaneous rates, lower maximum stimulus-evoked firing rates and more nonmonotonic rate-level curves for tones and noise. In addition, low-frequency type I units have lower thresholds to tones than corresponding LSO units. Taken together, these results suggest that the excitatory ILD pathway from LSO to ICC is mostly a high-frequency channel, and that additional inputs transform LSO influences in the ICC.

Response properties of single units in the dorsal nucleus of the lateral lemniscus of decerebrate cats.

The dorsal nucleus of the lateral lemniscus (DNLL) receives afferent inputs from many brain stem nuclei and, in turn, is a major source of inhibitory inputs to the inferior colliculus (IC). The goal of this study was to characterize the monaural and binaural response properties of neurons in the DNLL of unanesthetized decerebrate cat. Monaural responses were classified according to the patterns of excitation and inhibition observed in contralateral and ipsilateral frequency response maps. Binaural classification was based on unit sensitivity to interaural level differences. The results show that units in the DNLL can be grouped into three distinct types. Type v units produce contralateral response maps that show a wide V-shaped excitatory area and no inhibition. These units receive ipsilateral excitation and exhibit binaural facilitation. The contralateral maps of type i units show a more restricted I-shaped region of excitation that is flanked by inhibition. Type o maps display an O-shaped island of excitation at low stimulus levels that is bounded by inhibition at higher levels. Both type i and type o units receive ipsilateral inhibition and exhibit binaural inhibition. Units that produce type v maps have a low best frequency (BF), whereas type i and type o units have high BFs. Type v and type i units give monotonic rate-level responses for both BF tones and broadband noise. Type o units are inhibited by tones at high levels, but are excited by high-level noise. These results show that the DNLL can exert strong, differential effects in the IC.

Mechanics of transient platelet adhesion to von Willebrand factor under flow.

A primary and critical step in platelet attachment to injured vascular endothelium is the formation of reversible tether bonds between the platelet glycoprotein receptor Ibalpha and the A1 domain of surface-bound von Willebrand factor (vWF). Due to the platelet's unique ellipsoidal shape, the force mechanics involved in its tether bond formation differs significantly from that of leukocytes and other spherical cells. We have investigated the mechanics of platelet tethering to surface-immobilized vWF-A1 under hydrodynamic shear flow. A computer algorithm was used to analyze digitized images recorded during flow-chamber experiments and track the microscale motions of platelets before, during, and after contact with the surface. An analytical two-dimensional model was developed to calculate the motion of a tethered platelet on a reactive surface in linear shear flow. Through comparison of the theoretical solution with experimental observations, we show that attachment of platelets occurs only in orientations that are predicted to result in compression along the length of the platelet and therefore on the bond being formed. These results suggest that hydrodynamic compressive forces may play an important role in initiating tether bond formation.