Temporal coding of the periodicity of monaural and binaural complex tones in the guinea pig auditory brainstem Sami Alsindi Centre for the Neural Basis of Hearing, The Physiological Laboratory, University of Cambridge This dissertation is submitted to the University of Cambridge for the degree of Doctor of Philosophy, July 2017 Declaration II Declaration This dissertation is the result of my own work and includes nothing which is the outcome of work done in collaboration except as declared in the Preface and specified in the text. It is not substantially the same as any that I have submitted, or, is being concurrently submitted for a degree or diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text. I further state that no substantial part of my dissertation has already been submitted, or, is being concurrently submitted for any such degree, diploma or other qualification at the University of Cambridge or any other University or similar institution except as declared in the Preface and specified in the text It does not exceed the 60000 word limit prescribed by the Degree Committee of Biology. Sami Alsindi Corpus Christi College, Cambridge July 2017 Summary III Summary Sami Alsindi Temporal coding of the periodicity of monaural and binaural complex tones in the guinea pig auditory brainstem Humans report a strong pitch percept in response to a complex tone – the sum of a series of harmonics – presented to either a single ear (‘monaurally’) or both ears (‘diotically’). Interspike interval histograms of responses of neurons in the auditory system to monaural complex tones show a peak at the period of the pitch reported by humans – a ‘neural correlate of pitch’. However, the same pitch percept can be generated by presenting complexes with harmonics distributed across both ears (‘dichotically’). This requires combination of the neural signals underlying pitch from both sides of the auditory system, termed ‘binaural fusion’. Temporal coding generally deteriorates along the auditory pathway; binaural fusion should occur at a relatively early stage. One of the prime candidates is in the superior olivary complex (SOC). Although the guinea pig auditory system has been extensively studied, this work is the first in vivo investigation of the guinea pig SOC. Cells of the lateral superior olive (LSO) show sensitivity to interaural level differences; medial superior olive (MSO) cells show sensitivity to interaural time differences. Additionally, cells with responses similar to the medial nucleus of the trapezoid body (MNTB) and superior paraolivary nucleus (SPN) of other species were found in the guinea pig SOC. Presumed MNTB cells showed a three-component spike waveform shape; presumed SPN cells responded at the offset of contralaterally-presented stimuli. MSO and LSO cells respond to the overall pitch of complex tones, even if the monaural waveforms presented to each ear differ; this is consistent with the perception of humans. In contrast, cells of the ventral cochlear nucleus, which provide the main input to MSO and LSO cells, do not show evidence of a binaural pitch response. In conclusion, SOC cells are able to encode the pitch of binaural complex tones in their spike timing patterns. Acknowledgements IV Acknowledgements I originally applied to Cambridge to be a Biochemist, of all things! After the best three lectures I have ever attended, I soon realised the error of my ways. In one of those lectures, I was introduced to the tonotopy of the cochlea and was riveted (I may have kept the lecturer behind for an hour after a Saturday lecture asking questions!). Thank you, David Tolhurst, not only for this but also for being a very supportive Advisor during my PhD. For a 2nd year summer project, I looked to Cambridge-based Principal Investigators. Thankfully, the PI I was most interested in working with (Ian) responded and invited me to his lab, where he introduced me to the neurophysiological study of pitch in the auditory system. It seemed like the perfect confluence of my two passions: neuroscience and music. There, he introduced me to a type of pitch stimulus that was generated by what sounded like mere white noise in each headphone on its own but, when listened together, produced a clear pitch percept. I was baffled, and knew that binaural pitch was what I wanted to investigate. Of course it should go without saying that I thank my supervisor, Ian Winter, for not only sparking my interest in this field, but also providing a great environment in which to carry out such an interesting PhD project, and his invaluable contribution to my scientific understanding and training. It’s been a fantastic three-and-a-half years. Throughout my PhD, Arkadiusz ‘Arek’ Stasiak, a postdoc in our lab, offered tremendous scientific and personal support. He helped immensely with development of my computer programming skills, for which I cannot ever thank him enough. We went on to become good friends, both in and out of the lab, although I can’t rule out that this was due to the excellent electrodes he manufactured, which facilitated the best experiments of my PhD! I owe an enormous debt of gratitude to Anita Shelley and Mel Quy, who provided excellent training for the histology crucial to this Thesis. Thanks also goes to Mark Sayles, Roy Patterson, Ray Meddis, Hedwig Gockel, Jan Diepenbrock, Nihaad Paraouty, Alex Billig, Alan Archer-Boyd and many, many others for stimulating discussions and for making my PhD such an enjoyable one. An endless thanks goes to my father Zuhair and my mother Sahar, who were instrumental in instilling an early love of science, and, along with my brothers Wassim and Nabeel, somehow managed to put up with my antics over the years. However, above all, I need to express my gratitude for the one thing that was able to pull me through the long nights of searching for MSO units: the DeLonghi MAGNIFICA coffee machine. I couldn’t have done it without you… Sami Alsindi, July 2017 Contents V Table of Contents Declaration .......................................................................................................................... II Summary ............................................................................................................................ III Acknowledgements ........................................................................................................... IV Table of Contents ............................................................................................................... V List of Abbreviations ......................................................................................................... IX 1 General introduction ................................................................................................... 1 1.1 Overview ................................................................................................................ 2 1.2 Basic auditory pathway ........................................................................................... 2 1.2.1 External and middle ear ................................................................................... 2 1.2.2 Cochlea ........................................................................................................... 3 1.2.3 Auditory nerve ................................................................................................. 6 1.2.4 Cochlear nucleus ............................................................................................. 6 1.2.5 Superior olivary complex ................................................................................. 7 1.2.5.1 Mechanisms affecting MSO ITD-sensitivity .................................................. 9 1.2.6 Inferior colliculus ............................................................................................ 11 1.3 Pitch ..................................................................................................................... 12 1.3.1 Periodicity ...................................................................................................... 13 1.3.2 Place coding and resolvability ........................................................................ 17 1.3.3 Temporal coding of pitch ............................................................................... 19 1.3.4 Brainstem and midbrain models of pitch ........................................................ 21 1.4 Binaural integration ............................................................................................... 22 1.4.1 Binaural advantage ........................................................................................ 23 1.4.2 Azimuthal sound source localisation .............................................................. 24 1.4.3 Binaural pitch ................................................................................................. 25 1.4.3.1 Binaural pitch models ................................................................................. 27 1.4.3.2 Central pitch processor .............................................................................. 28 1.5 Thesis outline ....................................................................................................... 28 2 Methods ..................................................................................................................... 31 2.1 Experimental procedure .......................................................................................