Editing Tonotopy (section)

=== Peripheral nervous system ===

==== Cochlea ====
Tonotopic organization in the cochlea forms throughout pre- and post-natal development through a series of changes that occur in response to auditory stimuli.<ref>{{cite journal | vauthors = Mann ZF, Kelley MW | title = Development of tonotopy in the auditory periphery | journal = Hearing Research | volume = 276 | issue = 1–2 | pages = 2–15 | date = June 2011 | pmid = 21276841 | doi = 10.1016/j.heares.2011.01.011 | s2cid = 38361485 }}</ref> 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.<ref>{{cite journal | vauthors = Kandler K, Clause A, Noh J | title = Tonotopic reorganization of developing auditory brainstem circuits | journal = Nature Neuroscience | volume = 12 | issue = 6 | pages = 711–7 | date = June 2009 | pmid = 19471270 | pmc = 2780022 | doi = 10.1038/nn.2332 }}</ref> 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.<ref>{{Cite journal|date=May 1990|title=Development alterations in the frequency map of the mammalian cochlea|journal=American Journal of Otolaryngology|volume=11|issue=3|pages=207|doi=10.1016/0196-0709(90)90041-s|issn=0196-0709}}</ref> Research has suggested that the [[Guanylate cyclase-coupled receptor|receptor guanylyl cyclase]] [[NPR2|Npr2]] is vital for the precise and specific organization of this tonotopy.<ref>{{cite journal | vauthors = Lu CC, Cao XJ, Wright S, Ma L, Oertel D, Goodrich LV | title = Mutation of Npr2 leads to blurred tonotopic organization of central auditory circuits in mice | journal = PLOS Genetics | volume = 10 | issue = 12 | pages = e1004823 | date = December 2014 | pmid = 25473838 | pmc = 4256264 | doi = 10.1371/journal.pgen.1004823 | doi-access = free }}</ref> Further experiments have demonstrated a conserved role of [[Sonic hedgehog|Sonic Hedgehog]] emanating from the notochord and floor plate in establishing tonotopic organization during early development.<ref>{{cite journal | vauthors = Son EJ, Ma JH, Ankamreddy H, Shin JO, Choi JY, Wu DK, Bok J | title = Conserved role of Sonic Hedgehog in tonotopic organization of the avian basilar papilla and mammalian cochlea | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 12 | pages = 3746–51 | date = March 2015 | pmid = 25775517 | pmc = 4378437 | doi = 10.1073/pnas.1417856112 | bibcode = 2015PNAS..112.3746S | doi-access = free }}</ref> It is this proper tonotopic organization of the hair cells in the cochlea that allows for correct perception of frequency as the proper pitch.<ref>{{cite journal | vauthors = Oxenham AJ, Bernstein JG, Penagos H | title = Correct tonotopic representation is necessary for complex pitch perception | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 5 | pages = 1421–5 | date = February 2004 | pmid = 14718671 | pmc = 337068 | doi = 10.1073/pnas.0306958101 | doi-access = free }}</ref>

==== Structural organization ====

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).<ref name=":2">{{Citation|last=Dallos|first=Peter|chapter=Overview: Cochlear Neurobiology|date=1996|pages=1–43|editor-last=Dallos|editor-first=Peter| name-list-style = vanc |series=Springer Handbook of Auditory Research|publisher=Springer New York|language=en|doi=10.1007/978-1-4612-0757-3_1|isbn=9781461207573|editor2-last=Popper|editor2-first=Arthur N.|editor3-last=Fay|editor3-first=Richard R.|title=The Cochlea|volume=8}}</ref> 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.<ref name=":2" /> High frequency sounds stimulate neurons at the base of the structure and lower frequency sounds stimulate neurons at the apex.<ref name=":2" /> 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.<ref name=":2" /> For example, the BM increases in stiffness towards its base.

==== Mechanisms of cochlear tonotopy ====

Hair bundles, or the “mechanical antenna” of [[hair cell]]s, are thought to be particularly important in cochlear tonotopy.<ref name=":2" /> The morphology of hair bundles likely contributes to the BM gradient. Tonotopic position determines the structure of hair bundles in the cochlea.<ref name=":3">{{cite journal | vauthors = LeMasurier M, Gillespie PG | title = Hair-cell mechanotransduction and cochlear amplification | journal = Neuron | volume = 48 | issue = 3 | pages = 403–15 | date = November 2005 | pmid = 16269359 | doi = 10.1016/j.neuron.2005.10.017 | s2cid = 8002615 | doi-access = free }}</ref> 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).<ref name=":3" />

Furthermore, in the tip-link complex of cochlear hair cells, tonotopy is associated with gradients of intrinsic mechanical properties.<ref name=":4">{{cite journal | vauthors = Tobin M, Chaiyasitdhi A, Michel V, Michalski N, Martin P | title = Stiffness and tension gradients of the hair cell's tip-link complex in the mammalian cochlea | journal = eLife | volume = 8 | pages = e43473 | date = April 2019 | pmid = 30932811 | pmc = 6464607 | doi = 10.7554/eLife.43473  | doi-access = free }}</ref> 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.<ref name=":3" />  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.<ref name=":4" />

Tonotopy also manifests in the electrophysical properties of transduction.<ref name=":4" /> 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.<ref name=":5">{{cite journal | vauthors = He DZ, Jia S, Dallos P | title = Mechanoelectrical transduction of adult outer hair cells studied in a gerbil hemicochlea | journal = Nature | volume = 429 | issue = 6993 | pages = 766–70 | date = June 2004 | pmid = 15201911 | doi = 10.1038/nature02591 | bibcode = 2004Natur.429..766H | s2cid = 4422628 }}</ref> As noted above, basal cochlear hair cells have more stereocilia, thus providing more channels and larger currents.<ref name=":5" /> 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.<ref>{{cite journal | vauthors = Ricci AJ, Crawford AC, Fettiplace R | title = Tonotopic variation in the conductance of the hair cell mechanotransducer channel | journal = Neuron | volume = 40 | issue = 5 | pages = 983–90 | date = December 2003 | pmid = 14659096 | doi = 10.1016/S0896-6273(03)00721-9 | s2cid = 18002732 | doi-access = free }}</ref>

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.<ref name=":2" />