We know much about the way the peripheral parts of the hearing system process sounds. However, the subsequent processing of this information by neurones in the more central parts of the auditory system is much less well understood. We are attempting to understand the complex circuits and pathways involved in these processes by mapping them anatomically, measuring their functional responses physiologically and by combining these approaches with reversibly inactivating parts of them.

These projects are basic research, but they provide the underpinning for technologies being developed to manage profound hearing impairment, such as the new generation of auditory brainstem and midbrain implants.

Figure 1. The frequency level response area of a single neurone in the inferior colliculus showing a typical “V” shaped region of excitatory frequencies flanked by inhibition. The cell was filled with dye and then reconstructed in three dimensions to show its laminar connections within the inferior colliculus.

We investigate the normal auditory nervous system using combinations of neuroanatomical methods such as single neurone reconstruction (Figure 1), histochemistry (Figure 2), tract tracing, and neurophysiological methods such as iontophoresis, single and multi electrode recording and stimulation. In one project, we combine various neurophysiological measures with detailed reconstruction of filled neurones (see Figure 1). Here, we are seeking to determine the form and extent of both the dendrites and axons of cells intrinsic to the auditory midbrain and link them to the different physiological response profiles. We are using similar techniques in the auditory cortex to record from neurones (such as the pyramidal cells in Figure 2) and reconstruct their connections. In further studies we seek to link up our work in animal models with human neuroanatomy (Figure 2) combining traditional neuroanatomical techniques with functional magnetic resonance imaging.

Figure 2. Pyramidal cells in layer five of the human auditory cortex stained for Acetylcholinesterase.

Recent studies have implicated the profuse descending connections from the cortex (illustrated in Figure 3) in a variety of functions such as plasticity, learning and attention. We are beginning to address these functions by reversibly inactivating the cortex while monitoring the effects at the thalamic, midbrain and cochlear levels (Figure 3). Such studies will provide a basis for understanding the modulation of sensory abilities by attention and the plastic changes that take place as a result of learning or pathology.

Figure 3. Schematic diagram of the ascending (black arrows) and descending (red arrows) auditory system. We inactivate the cortex by cooling, while recording neural spiking responses from auditory midbrain (inferior colliculus) and thalamus (medialGeniculate body) or gross potentials from the cochlea.

We use computational models to ask how it is that the auditory system might be accomplishing a particular processing feat. For example – following an injury to a specific part of the cochlea, the auditory system rapidly ‘reorganises’ itself so that neurons that used to represent the damaged region of the cochlea now represent undamaged regions. We have shown that even a simple model of dendritic processing in a single neuron (figure 2) can produce this ‘reorganising’ without any modification of synapses. Understanding how the brain manages to cope so well with damage to our ears not only helps to understand the consequences of hearing loss, but also tells us more generally about how the brain is able to process sound so flexibly.