Tonotopy

In physiology, tonotopy (from Greek tono=frequency and topos = place) is the spatial arrangement of where sounds of different frequency are processed in the brain. Tones close to each other in terms of frequency are represented in topologically neighbouring regions in the brain. Tonotopic maps are a particular case of topographic organization, similar to retinotopy in the visual system. In physiology, tonotopy (from Greek tono=frequency and topos = place) is the spatial arrangement of where sounds of different frequency are processed in the brain. Tones close to each other in terms of frequency are represented in topologically neighbouring regions in the brain. Tonotopic maps are a particular case of topographic organization, similar to retinotopy in the visual system. Tonotopy in the auditory system begins at the cochlea, the small snail-like structure in the inner ear that sends information about sound to the brain. Different regions of the basilar membrane in the organ of Corti, the sound-sensitive portion of the cochlea, vibrate at different sinusoidal frequencies due to variations in thickness and width along the length of the membrane. Nerves that transmit information from different regions of the basilar membrane therefore encode frequency tonotopically. This tonotopy then projects through the vestibulocochlear nerve and associated midbrain structures to the primary auditory cortex via the auditory radiation pathway.Throughout this radiation, organization is linear with relation to placement on the organ of Corti, in accordance to the best frequency response (that is, the frequency at which that neuron is most sensitive) of each neuron. However, binaural fusion in the superior olivary complex onward adds significant amounts of information encoded in the signal strength of each ganglion. Thus, the number of tonotopic maps varies between species and the degree of binaural synthesis and separation of sound intensities; in humans, six tonotopic maps have been identified in the primary auditory cortex. their anatomical locations along the auditory cortex. The earliest evidence for tonotopic organization in auditory cortex was indicated by Vladimir E. Larionov in an 1899 paper entitled 'On the musical centers of the brain', which suggested that lesions in an S-shaped trajectory resulted in failure to respond to tones of different frequencies. By the 1920s, cochlear cochlear anatomy had been described and the concept of tonotopicity had been introduced. At this time, Hungarian biophysicist, Georg von Békésy began further exploration of tonotopy in the auditory cortex. Békésy measured the cochlear traveling wave by opening up the cochlea widely and using a strobe light and microscope to visually observe the motion on a wide variety of animals including guinea pig, chicken, mouse, rat, cow, elephant, and human temporal bone. Importantly, Békésy found that different sound frequencies caused maximum wave amplitudes to occur at different places along the basilar membrane along the coil of the cochlea, which is the fundamental principal of tonotopy. Békésy was awarded the  Nobel Prize in Physiology or Medicine  for his work. In 1946, the first live demonstration of tonotopic organization in auditory cortex occurred at John Hopkins Hospital. More recently, advances in technology have allowed researchers to map the tonotopic organization in healthy human subjects using electroencephalographic (EEG) and magnetoencephalographic (MEG) data. While most human studies agree on the existence of a tonotopic gradient map in which low frequencies are represented laterally and high frequencies are represented medially around Heschl's gyrus, a more detailed map in human auditory cortex is not yet firmly established due to methodological limitations Tonotopic organization in the cochlea forms throughout pre- and post-natal development through a series of changes that occur in response to auditory stimuli. Research suggests that the pre-natal establishment of tonotopic organization is partially guided by synaptic reorganization; however, more recent studies have shown that the early changes and refinements occur at both the circuit and subcellular levels. In mammals, after the inner ear is otherwise fully developed, the tonotopic map is then reorganized in order to accommodate higher and more specific frequencies. Research has suggested that the receptor guanylyl cyclase Npr2 is vital for the precise and specific organization of this tonotopy. Further experiments have demonstrated a conserved role of Sonic Hedgehog emanating from the notochord and floor plate in establishing tonotopic organization during early development. It is this proper tonotopic organization of the hair cells in the cochlea that allows for correct perception of frequency as the proper pitch. In the cochlea, sound creates a traveling wave that moves from base to apex, increasing in amplitude as it moves along a tonotopic axis in the basilar membrane (BM). This pressure wave travels along the BM of the cochlea until it reaches an area that corresponds to its maximum vibration frequency; this is then coded as pitch. High frequency sounds stimulate neurons at the base of the structure and lower frequency sounds stimulate neurons at the apex. This represents cochlear tonotopic organization. This occurs because the mechanical properties of the BM are graded along a tonotopic axis; this conveys distinct frequencies to hair cells (mechanosensory cells that amplify cochlear vibrations and send auditory information to the brain), establishing receptor potentials and, consequently frequency tuning. For example, the BM increases in stiffness towards its base. Hair bundles, or the “mechanical antenna” of hair cells, are thought to be particularly important in cochlear tonotopy. The morphology of hair bundles likely contributes to the BM gradient. Tonotopic position determines the structure of hair bundles in the cochlea. The height of hair bundles increases from base to apex and the number of stereocilia decreases (i.e. hair cells located at the base of the cochlea contain more stereo cilia than those located at the apex). Furthermore, in the tip-link complex of cochlear hair cells, tonotopy is associated with gradients of intrinsic mechanical properties. In the hair bundle, gating springs determine the open probability of mechanoelectrical ion transduction channels: at higher frequencies, these elastic springs are subject to higher stiffness and higher mechanical tension in tip-links of hair cells.  This is emphasized by the division of labor between outer and inner hair cells, in which mechanical gradients for outer hair cells (responsible for amplification of lower frequency sounds) have higher stiffness and tension. Tonotopy also manifests in the electrophysical properties of transduction. Sound energy is translated into neural signals through mechanoelectrical transduction. The magnitude of peak transduction current varies with tonotopic position. For example, currents are largest at high frequency positions such as the base of cochlea. As noted above, basal cochlear hair cells have more stereocilia, thus providing more channels and larger currents. Tonotopic position also determines the conductance of individual transduction channels. Individual channels at basal hair cells conduct more current than those at apical hair cells. Finally, sound amplification is greater in the basal than in the apical cochlear regions because outer hair cells express the motor protein prestin, which amplifies vibrations and increases sensitivity of outer hair cells to lower sounds.