Give a detailed account of how the auditory system manage to code for sounds of different frequency and intensity

and to discriminate sounds in the presence of background noise. What would be the expected phenotype for a person lacking the gene coding for Prestin? Sound can be described as pressure waves in a medium (generally, air). Our perception of sound is a representation of these pressure waves, which is detected and processed by our auditory system. Frequency differentiation The sounds we hear in our daily life is generally complex, not just made up of single pure frequencies of sound waves. To perceive complex sounds, it has been shown that our auditory system first breaks down complex sound with a wide range of spectral frequencies into pure sinusoidal frequencies, which is then added up together at higher levels of processing in the system to generate back the complex sound. It is evident that this type of processing, also known as Fourier analysis, is advantageous as the reduces the need for millions of different types of receptors each for a type of complex sound. A similar method is used by the visual system, which detects the composition of colours by three different types of photoreceptor cells and later summing the relative responses from each to 'regenerate' the image of colour. The auditory system's receptors for sound, therefore need to be able to differentiate their responses for different pure frequency components that make up the complex tone we hear, as well as able to tell the intensity (loudness) of the sound. Frequency differentiation takes place at the basilar membrane on the cochlear and the corresponding spiral ganglion cells that are receiving input from the movement of the membrane and translating it to electrical impulses that can be transmitted to higher levels of processing (where Fourier analysis is carried out). There are two methods that our auditory system uses to code frequency of sound. When sound waves are conducted to the inner ear, The basilar membrane in the cochlear vibrates along different points in space depending on the frequencies that reach, a phenomenon caused by the resonance of the basilar membrane to the frequency the base of the basilar membrane (at the oval window) is stiff and narrow, thus having a higher resonance frequency while the apex is more flexible and broad, corresponding to a lower resonance frequency. This spatial separation of frequencies on the basilar membrane is called tonotopy. Tonotopy fails to work at low frequencies (below 200 Hz) however, as there is no neurons with characteristic frequencies lower than 200 Hz. It would also be necessary to tell whether the basilar membrane movement is due to the signal falling at the particular frequency or is it just a result of being nearer an area that has a large intensity stimulus (refer to later section on intensity). There is thus another mechanism to differentiate frequencies called phase-locking, which takes place at the level of neural firing of the spiral ganglion cells receiving synaptic inputs from the cochlear. The timings of the action potentials (APs) generated by these cells are such that the APs always occur at a specific phase of the stimulus frequency (also at a specific phase of the vibration of the basilar membrane).

Fig. Phase-locking mechanism of the auditory nerve fibres.

APs may not be fired at each cycle, but by taking the overall response from several nerves, the number of cycles per second (therefore frequency) can be computed. This mechanism fails at high frequencies (greater than 4kHz) as the intrinsic variability in the firing of an action potential becomes comparable to the time interval between each cycle. Therefore for high frequencies, the tonotopic map of the basilar membrane is used to determine frequency, at low frequencies phase locking by the neuronal response is used and at intermediate frequencies, both mechanism can be used. Intensity differentiation Intensity of a stimulus is firstly coded by the rate of firing of the neurons at the spiral ganglion, which are synapsed to inner hair cells (IHCs). A high intensity sound causes a large vibration in the basilar membrane, resulting in a greater magnitude of deflection of the stereocilia on IHCs. This mechanical movement of the stereocilia against the tectorial membrane is translated into tension in the tip-links of the stereocilia, which are linked to stretch-sensitive potassium (K) channels. A schematic representation of this process is shown below:

Fig. Tension in tip links caused by deflection of the stereocilia opens ion channels. When the deflection is increased by a higher intensity sound, the tip links are stretched more, and open more stretch-sensitive channels. This will result in a larger amount of current (positive K ions) flowing into the cell per unit time. The change in membrane potential due to the inward K current opens voltage-dependent calcium channels which increases cytosolic concentration of Ca in the IHCs. Calcium-dependent exocytosis is then triggered in the IHCs to release neurotransmitters, which induces changes in potential in the neurons that are synapsed to the IHCs.

Fig. Depolarisation opens Ca channels triggering neurotransmitter release. The high intensity signal will result in the amplification of inward K current per unit time, which causes a larger Ca current and in turn trigger more neurotransmitter release. As such the threshold at the spiral ganglion neurite can be reached faster, thus increasing the rate that the neuron can fire an action potential.

While the basilar membrane vibrates more at the resonance frequency of the stimulus, the larger amplitude of vibration also spreads to the areas around the resonance frequency, due to the rigid nature of the membrane. This activates more neurons at areas around the resonance frequency as the amplitude of deflection has increased as compared to a low intensity sound of the same frequency. Therefore, the intensity of a sound is encoded by both the rate of firing of neurons that corresponds to the signal frequency as well as the number of neurons that fire around the region in resonance with the signal frequency. Discriminating sounds in background noise An attenuation reflex mediated by the tensor tympani muscles and stapedius in the middle ear allows for adaptation of the system to background noise, therefore increasing the dynamic range of hearing. Exposure to loud background noises, tend to saturate the receptor responses, making it hard to discriminate sounds. Contraction of the above mentioned muscles in the middle ear make the chains of ossicles more rigid, and thus more difficult to be moved by displacements of the tympanic membrane due to sound pressure. Sound conduction in the middle ear is therefore diminished, especially for low frequencies. This attenuation effect is conducted through neural response to the muscles by the onset of a loud sound. The attenuation of low frequency noise in the background makes higher-frequency sounds easier to discern. The function of Prestin Besides the IHCs which conduct the mechanical motion of the basilar membrane into depolarisations, there are another set of cells with stereocilia which sits on the basilar membrane known as outer hair cells (OHCs) (they are collectively in a structure called the organ of Corti, on top of the basilar membrane. These cells are far greater in number (three times more in humans) than IHCs but are generally not involved in generating spikes in the spiral ganglion cells synapsed to them. These cells are instead involved more in the active mechanism of amplifying the resonance response on the basilar membrane, and are thus also called the cochlear amplifier. The stereocilia of the OHCs work in the same way as the IHCs (as outlined above). When the inward K current changes the membrane potential, intracellular anions are thought to act as voltage sensors and bind to motor proteins in the OHCs. This causes the motor proteins to lengthen and shorten the OHCs in phase with the vibrations on the basilar membrane, thus amplifying the signal for up to a hundred times. One prominent candidate for this motor protein is Prestin. This protein is packed into the lateral sides of the OHCs and required for rapid length changes in the OHCs. Studies (Liberman et. Al, 2002) have shown that when the gene coding for Prestin is deleted from mice, they become nearly deaf. Animals with auditory systems can detect sound energy from the environment and reconstruct these as perceived sounds. The detection and differentiation can happen at many levels, two many dimensions of variable being intensity and frequency, which are tuned and amplified by said auditory system. This presents us with yet another way of perceiving the world around us. References 1. Bear MF, Connors BW, Paradiso MA. Neuroscience: Exploring the Brain. Lippincott Willians and Wilkins. 2001. 2. Liberman MC, Gao J, He DZ, Wu X, Jia S, Zuo J. Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier. September 2002. Nature 419 (6904): 3004