Semester

Summer

Date of Graduation

2011

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Microbiology, Immunology, and Cell Biology

Committee Chair

George A Spirou

Abstract

The medial and lateral superior olives (MSO, LSO) are the lowest order cell groups in the mammalian auditory circuit to receive massive binaural input. The MSO functions in part to encode interaural time differences (ITD), the predominant cue for localization of low frequency sounds. Binaural inputs to the MSO consist of excitatory projections from the cochlear nuclei (CN) and inhibitory projections from both the medial nucleus of the trapezoid body (MNTB) and lateral nucleus of the trapezoid body (LNTB). The interaction of excitatory and inhibitory currents within an MSO cell's soma and dendrites over the backdrop of its intrinsic ionic conductances imbues ITD sensitivity to these neurons. Lloyd Jeffress proposed a coincidence detection circuit in which arrays of neurons receive sub-threshold excitatory inputs via delay lines that represent sound location as a place code of activity patterns within the cell group (Jeffress, 1948). The Jeffress place code model later found a neural instantiation in the MSO. Recent in vivo (McAlpine et al., 2001; Brand et al., 2002) studies have shown that peak discharge rates do not fall within the ecological range as the Jeffress model predicts but instead ITD is coded by changes in discharge rate. The timing of inhibition relative to excitation modulates the discharge rates of MSO cells (Brand et al., 2002; Chirila et al., 2007); however, the details of this circuit, such as the onset time of inhibition, are not well known. Although the MNTB and LNTB have been investigated in vivo and in vitro , they have not been well characterized with respect to their function in ITD processing in larger mammals. Additionally, inhibition is modulated by anesthesia and confounds in vivo experiments that examine the careful interplay of excitatory and inhibitory effects in the MSO. For this reason, these physiological experiments were performed on decerebrate unanaesthetized animals. Further investigation of the anatomical organization of inhibitory inputs was carried out as the basis for a comprehensive model of the MSO that incorporates the effects of binaural inhibiting projections to MSO neurons.;Unbiased stereological counts of the MNTB, MSO and subdivisions of the LNTB showed that the MSO and MNTB contain approximately the same number of cells. The main (m)LNTB, posteroventral (pv)LNTB and the hilus (h)LNTB are estimated to contain 3800, 1400, and 200 neurons respectively. Tonotopic organization of the MNTB and MSO show that in the low frequency area, MSO cells outnumber MNTB cells 2 to 1, suggesting a divergent innervation of the MSO from the MNTB. Injection of the retrograde tracer, biotinylated dextrane amine, in the MSO, labeled cells in the MNTB, pvLNTB and mLNTB and defines the important role that these sub-nuclei, and in particular the pvLNTB, have in ITD coding. Computational modeling of a single MSO cell suggests that when two sources of inhibition temporally frame excitation the coincidence detection window is refined and less sensitive to temporal fluctuations that otherwise might degrade ITD sensitivity. Finally, physiological properties of MNTB cells reveal a heterogeneous population of responses and less precise temporal coding than are found in their inputs, globular bushy cells.

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