COMPARATIVE AUDITORY NEUROSCIENCE LAB

"Nothing in biology makes sense except in the light of evolution"

(Theodosius Dobzhansky, 1973, The American Biology Teacher 35:125-129)

How did the sensory and nervous systems of animals evolve within the context of their environment? What is the system capable of and how did it arrive there? How do different evolutionary solutions to the same problem compare and what can we learn from this?
Our model for studying these basic questions is the auditory system of vertebrates. We are interested in the sensory elements of the inner ear as well as the first stages of neural processing of auditory stimuli.

....... more about current projects

The neural basis of sound localisation

Localisation of stimuli is an essential task of sensory systems. The localisation of sound is less straightforward than for most other senses. Unlike, e.g., the retina of the eye, the auditory receptor organ, the cochlea, contains no map-like representation of stimulus location. Sound localisation is a computational problem that has to be solved by the central auditory pathways in the brain. Animals and humans use the minute differences in the timing and intensity of the acoustic input to both ears: When sound comes from one side of the body, it reaches one ear before the other and it is louder in that ear. These so-called interaural differences are computed by the brain by comparing the inputs from both ears and are used to synthesise a neural map of auditory space.
Many steps are involved in this and the individual stages of neural processing are quite well known for the derivation of interaural time differences. Research on barn owls has contributed much to our understanding of temporal processing in the auditory system. New data from small mammals, however, have pointed out inconsistencies with the processing model established in the barn owl and have lead to the suggestion of an alternative mechanism for coding interaural time differences.
Together with Prof. Catherine Carr, we are recording from the relevant brainstem centre (Nucleus laminaris) in chickens and barn owls to learn more about the neural coding of interaural time differences across frequencies and across species.

The black structure in this microscope image is a single dye-labelled nerve cell in the chicken's brainstem. This particular neurone responded best when sound in the left ear was leading the same sound in the right ear by 60 µs. For the chicken, this means a sound originating from about 30° to its left. Neighbouring neurones responded best to other time differences, together they form a map of horizontal auditory space.

An example for the neural circuits involved in the barn owl's brainstem. This is a schematic drawing reconstructing the projections (red) of a single neurone whose cell body lay in Nucleus magnocellularis (outline in dark red). The axon bifurcates shortly after leaving the nucleus. The ipsilateral branch terminates at multiple sites within Nucleus laminaris (gray outlines, paling with depth); the other branch, which is only shown up to the brain's midline, travels to the contralateral Nucleus laminaris.

This scientific drawing caught the interest of Franz Mayrhofer, an artist in Vienna (Austria), and was used as a template for some beautiful variations made with acrylic paints and gold leaf.
see Kunstproduktion Franz Mayrhofer

Evolution of the cochlear efferent system

An important part of the peripheral auditory system is the feedback control returning from the brain to the sensory cells of the cochlea, termed the efferent system. The efferent system in mammals (and humans) is complex and despite a long history of research, its functions are still only partly known. Our approach is to study the different and mostly simpler forms of the efferent system in a variety of other vertebrate animals. This will enable us to separate its common, basic properties from more specialised functions added later in evolution.
The primitive condition is a small number of otic efferent neurones, many of them synapsing on a range of hair-cell endorgans, auditory, vestibular and, if present, lateral line. In the highly developed auditory systems of birds and mammals, there is a complete separation of efferents to the vestibular endorgans and efferents serving exclusively the cochlea. When did this separation occur and why? We are looking at amphibians, birds and reptiles to shed light on this question.

This little movie shows a fluorescent microscope view focussing through different layers of a basilar-papilla wholemount from a lizard. The bright green dots and fibre-like structures represent efferent synapses and axons, labelled with an antibody against ChAT (the enzyme which synthesises the major efferent transmitter). The outlines of the basilar papilla and some hair cells within are just discernable as the weaker fluorescence.

Examples of labelled efferent neurones in the barn owl's brainstem. Different tracer substances were introduced into the two ears of an individual animal, where they were taken up by the efferent synaptic terminals and transported retrogradely to the cell body in the brainstem. The two tracers were subsequently coupled to fluoresent markers of different colours. A minority of neurones (e.g. the cell in the middle of this image) is labelled with both colours, i.e. it sent axons to both inner ears.

The basis of cochlear amplification

A now firmly-established concept in auditory physiology is the active amplification of faint stimuli by the sensory cells, the hair cells. In mammals, the most favoured mechanism underlying this are membrane-based movements of the hair-cell body. There is strong evidence that the inner ears of amphibians, reptiles and birds can also actively generate mechanical energy. However, the mechanism underlying this is believed to reside in the mechanosensitive hair bundle at the top of the cell, not in the cell body. Both types of hair-cell motility are well characterized in vitro.
Together with Prof. Manley (Technische Universität München) and Dr. Yates (University of Western Australia), we showed for the first time that, in a lizard, hair bundle motions are indeed involved in vivo.
Together with Prof. Forge (University College, London) we showed, using freeze-fracture techniques, that the hair-cell membranes in birds and lizards lack the characteristic specializations which, in mammals, are causally linked to their motility. This is further evidence that membrane-based motility is indeed unique to mammals. Hair-bundle motility is probably involved in active amplification in all vertebrates, including the mammalian cochlea.
Together with Prof. Iwasa (NIH, USA) we are using quantitative anatomical data on bird hair cells to model hair-bundle motility and to determine whether it could provide significant amplification in the avian hearing range.

Two neighbouring hair cells from the apical third of the basilar papilla of a tokay gecko. Large areas of the cell membrane of both hair cells are fractured; at the top, parts of the stereovillar bundles can still be observed, albeit grossly displaced during tissue processing.

Development of the barn owl cochlea

The barn owl is a very well-known model for the neural mechanisms of sound localization. Owls are altricial birds, still growing immensely in the first weeks after hatching. During this time, the physical cues that are the basis of precise sound localization, i.e. interaural time and intensity differences, change continuously. Maturation of the relevant brainstem and midbrain centres has been shown to occur gradually over weeks and months, partly under the guidance of the visual system. It is unknown at present whether maturation of the sense organ, the cochlea, may also be contributing to these processes. Indeed, nothing is known about the young owl's inner ear. We therefore currently investigate the development of the barn owl's cochlea. Physiological data show that the animals probably hatch deaf and that there is a surprisingly prolonged period of cochlear maturation after hatching (2-3 months). Owl chicks should therefore be rewarding subjects for future experimental manipulations of their peripheral auditory development.

Development of the thresholds of the compound action potential (CAP) recorded at the cochlear round window, using pure-tone stimuli of different frequencies. Differently-coloured curves represent owlets of different ages (Pxx = days posthatching. Adult values are shown as medians and interquartile ranges.

Scanning electron microscopic surface views of individual hair cells in a 4-day old (A, C) and an adult (B, D) owl. The top two hair cells are from basal regions (80% of papillar length from the apex), the bottom two from apical regions (30% from the papillar apex). Note the many supernumerary villi in the immature bundles of the young hair cells.

The basis of fast temporal processing in the barn owl cochlea

The barn owl is a well-established model for the fast temporal processing used in measuring interaural time differences for localizing sound sources in space. The owl serves as an example for the extreme performance of a basic mechanism that is used by many animals, including humans. The basis for its extreme performance is already found at the level of the inner ear. Via neural phase locking, the afferent nerve fibres leaving the owl's cochlea for the brainstem code the temporal occurrence of a stimulus with a precision of up to 30µs. Although well documented, it is still unknown how that kind of precision is achieved. We believe that specializations both at the level of the hair cells and the afferent neurones are necessary. We have already shown that afferent axons are unusually heavily myelinated in the owl. Studies of the development of neural phase locking in the auditory nerve are underway. These will help to elucidate when and how experience-dependent refinement of the brainstem circuits using this crucial input takes place.

Temporal dispersion (or jitter) of phase coding in the auditory nerve as a function of stimulus frequency. The different curves show median values for large samples of single-unit data in different species of birds and mammals. Note the scaling in microseconds - this degree of temporal precision is an amazing feat of the auditory system! The barn owl (red curve) holds the record, with temporal dispersions below 30µs.