Editing Tonotopy (section)

=== Central nervous system ===

==== Cortex ====
Audio frequency, otherwise known as the pitch, is currently the only characteristic of sound that is known with certainty to be topographically mapped in the central nervous system. However, other characteristics may form similar maps in the cortex such as sound intensity,<ref>{{cite journal | vauthors = Bilecen D, Seifritz E, Scheffler K, Henning J, Schulte AC | title = Amplitopicity of the human auditory cortex: an fMRI study | journal = NeuroImage | volume = 17 | issue = 2 | pages = 710–8 | date = October 2002 | pmid = 12377146 | doi =  10.1006/nimg.2002.1133| s2cid = 12976735 }}</ref><ref>{{cite journal | vauthors = Pantev C, Hoke M, Lehnertz K, Lütkenhöner B | title = Neuromagnetic evidence of an amplitopic organization of the human auditory cortex | journal = Electroencephalography and Clinical Neurophysiology | volume = 72 | issue = 3 | pages = 225–31 | date = March 1989 | pmid = 2465125 | doi = 10.1016/0013-4694(89)90247-2 }}</ref> tuning bandwidth,<ref>{{cite journal | vauthors = Seifritz E, Di Salle F, Esposito F, Herdener M, Neuhoff JG, Scheffler K | title = Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence | journal = NeuroImage | volume = 29 | issue = 3 | pages = 1013–22 | date = February 2006 | pmid = 16253522 | doi = 10.1016/j.neuroimage.2005.08.029 | s2cid = 17432921 }}</ref> or modulation rate,<ref>{{cite journal | vauthors = Langner G, Sams M, Heil P, Schulze H | title = Frequency and periodicity are represented in orthogonal maps in the human auditory cortex: evidence from magnetoencephalography | journal = Journal of Comparative Physiology A | volume = 181 | issue = 6 | pages = 665–76 | date = December 1997 | pmid = 9449825 | doi = 10.1007/s003590050148 | s2cid = 2487323 }}</ref><ref>{{cite journal | vauthors = Herdener M, Esposito F, Scheffler K, Schneider P, Logothetis NK, Uludag K, Kayser C | title = Spatial representations of temporal and spectral sound cues in human auditory cortex | journal = Cortex; A Journal Devoted to the Study of the Nervous System and Behavior | volume = 49 | issue = 10 | pages = 2822–33 | date = November 2013 | pmid = 23706955 | doi = 10.1016/j.cortex.2013.04.003 | s2cid = 19454517 }}</ref><ref>{{cite journal | vauthors = Barton B, Venezia JH, Saberi K, Hickok G, Brewer AA | title = Orthogonal acoustic dimensions define auditory field maps in human cortex | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 50 | pages = 20738–43 | date = December 2012 | pmid = 23188798 | pmc = 3528571 | doi = 10.1073/pnas.1213381109 | bibcode = 2012PNAS..10920738B | doi-access = free }}</ref> but these have not been as well studied.

In the midbrain, there exist two primary auditory pathways to the auditory cortex—the [[lateral lemniscus|lemniscal]] classical auditory pathway and the extralemniscal non-classical auditory pathway.<ref name=":0">{{cite journal | vauthors = Saenz M, Langers DR | title = Tonotopic mapping of human auditory cortex | journal = Hearing Research | volume = 307 | pages = 42–52 | date = January 2014 | pmid = 23916753 | doi = 10.1016/j.heares.2013.07.016 | s2cid = 8705873 }}</ref> The lemniscal classical auditory pathway is tonotopically organized and consists of the central nucleus of the [[inferior colliculus]] and the ventral [[Medial geniculate nucleus|medial geniculate body]] projecting to primary areas in the auditory cortex. The non-primary auditory cortex receives inputs from the extralemniscal non-classical auditory pathway, which shows a diffuse frequency organization.<ref name=":0" />

The tonotopic organization of the [[auditory cortex]] has been extensively examined and is therefore better understood compared to other areas of the auditory pathway.<ref name=":0" /> Tonotopy of the auditory cortex has been observed in many animal species including birds, rodents, primates, and other mammals.<ref name=":0" /> '''In mice,''' four subregions of the auditory cortex have been found to exhibit tonotopic organization. The classically divided A1 subregion has been found to in fact be two distinct tonopic regions—A1 and the dorsomedial field (DM).<ref name=":1">{{cite journal | vauthors = Tsukano H, Horie M, Bo T, Uchimura A, Hishida R, Kudoh M, Takahashi K, Takebayashi H, Shibuki K | title = Delineation of a frequency-organized region isolated from the mouse primary auditory cortex | journal = Journal of Neurophysiology | volume = 113 | issue = 7 | pages = 2900–20 | date = April 2015 | pmid = 25695649 | pmc = 4416634 | doi = 10.1152/jn.00932.2014 }}</ref> Auditory cortex region A2 and the anterior auditory field (AAF) both have tonotopic maps that run dorsoventrally.<ref name=":1" /> The other two regions of the mouse auditory cortex, the dorsoanterior field (DA) and the dorsoposterior field (DP) are non-tonotopic. While neurons in these non-tonotopic regions have a characteristic frequency, they are arranged randomly.<ref>{{cite journal | vauthors = Guo W, Chambers AR, Darrow KN, Hancock KE, Shinn-Cunningham BG, Polley DB | title = Robustness of cortical topography across fields, laminae, anesthetic states, and neurophysiological signal types | journal = The Journal of Neuroscience | volume = 32 | issue = 27 | pages = 9159–72 | date = July 2012 | pmid = 22764225 | pmc = 3402176 | doi = 10.1523/jneurosci.0065-12.2012 }}</ref>

Studies using non-human primates have generated a hierarchical model of auditory cortical organization consisting of an elongated core consisting of three back-to-back tonotopic fields—the primary auditory field A1, the rostral field R, and the rostral temporal field RT. These regions are surrounded by belt fields (secondary) regions and higher-order parabelt fields.<ref>{{cite journal | vauthors = Hackett TA, Preuss TM, Kaas JH | title = Architectonic identification of the core region in auditory cortex of macaques, chimpanzees, and humans | journal = The Journal of Comparative Neurology | volume = 441 | issue = 3 | pages = 197–222 | date = December 2001 | pmid = 11745645 | doi = 10.1002/cne.1407 | s2cid = 21776552 }}</ref> A1 exhibits a frequency gradient from high to low in the posterior-to-anterior direction; R exhibits a reverse gradient with characteristic frequencies from low to high in the posterior-to-anterior direction. RT has a less clearly organized gradient from high back to low frequencies.<ref name=":0" /> These primary tonotopic patterns continuously extend into the surrounding belt areas.<ref>{{cite journal | vauthors = Kusmierek P, Rauschecker JP | title = Functional specialization of medial auditory belt cortex in the alert rhesus monkey | journal = Journal of Neurophysiology | volume = 102 | issue = 3 | pages = 1606–22 | date = September 2009 | pmid = 19571201 | pmc = 2746772 | doi = 10.1152/jn.00167.2009 }}</ref>

Tonotopic organization in the human auditory cortex has been studied using a variety of non-invasive imaging techniques including magneto- and electroencephalography ([[Magnetoencephalography|MEG]]/[[Electroencephalography|EEG]]), positron emission tomography ([[Positron emission tomography|PET]]), and functional magnetic resonance imaging ([[Functional magnetic resonance imaging|fMRI]]).<ref>van Dijk, P., & Langers, D. R. M. (2013). [https://link.springer.com/chapter/10.1007%2F978-1-4614-1590-9_46 "Mapping Tonotopy in Human Auditory Cortex"] In B. C. J. Moore, R. D. Patterson, I. M. Winter, R. P. Carlyon, & H. E. Gockel (Eds.), ''Basic Aspects of Hearing'' (Vol. 787, pp. 419–425). https://doi.org/10.1007/978-1-4614-1590-9_46</ref> The primary tonotopic map in the human auditory cortex is along [[Transverse temporal gyrus|Heschl's gyrus]](HG). However, various researchers have reached conflicting conclusions about the direction of frequency gradient along HG. Some experiments found that tonotopic progression ran parallel along HG while others found that the frequency gradient ran perpendicularly across HG in a diagonal direction, forming an angled V-shaped pair of gradients.<ref name=":0" />

==== In mice ====
One of the well-established methods of studying tonotopic patterning in the auditory cortex during development is tone-rearing.<ref name=Barkat2011>{{cite journal | vauthors = Barkat TR, Polley DB, Hensch TK | title = A critical period for auditory thalamocortical connectivity | journal = Nature Neuroscience | volume = 14 | issue = 9 | pages = 1189–94 | date = July 2011 | pmid = 21804538 | pmc = 3419581 | doi = 10.1038/nn.2882 }}</ref><ref name=deVillers2007>{{cite journal | vauthors = de Villers-Sidani E, Chang EF, Bao S, Merzenich MM | title = Critical period window for spectral tuning defined in the primary auditory cortex (A1) in the rat | journal = The Journal of Neuroscience | volume = 27 | issue = 1 | pages = 180–9 | date = January 2007 | pmid = 17202485 | pmc = 6672294 | doi = 10.1523/JNEUROSCI.3227-06.2007 | url = https://escholarship.org/content/qt20p2h3wt/qt20p2h3wt.pdf?t=lnr8r3 }}</ref>  In mouse Primary [[Auditory cortex|Auditory Cortex]] (A1), different neurons respond to different ranges of frequencies with one particular frequency eliciting the largest response – this is known as the "best frequency" for a given neuron.<ref name=Barkat2011 /> Exposing mouse pups to one particular frequency during the auditory critical period (postnatal day 12 to 15)<ref name=Barkat2011 /> will shift the "best frequencies" of neurons in A1 towards the exposed frequency tone.<ref name=Barkat2011 />

These frequency shifts in response to environmental stimuli have been shown to improve performance in perceptual behavior tasks in adult mice that were tone-reared during auditory critical period.<ref>{{cite journal | vauthors = Han YK, Köver H, Insanally MN, Semerdjian JH, Bao S | title = Early experience impairs perceptual discrimination | journal = Nature Neuroscience | volume = 10 | issue = 9 | pages = 1191–7 | date = September 2007 | pmid = 17660815 | doi = 10.1038/nn1941 | s2cid = 11772101 }}</ref><ref>{{cite journal | vauthors = Sarro EC, Sanes DH | title = The cost and benefit of juvenile training on adult perceptual skill | journal = The Journal of Neuroscience | volume = 31 | issue = 14 | pages = 5383–91 | date = April 2011 | pmid = 21471373 | pmc = 3090646 | doi = 10.1523/JNEUROSCI.6137-10.2011 }}</ref> Adult learning and critical period sensory manipulations induce comparable shifts in cortical topographies, and by definition adult learning results in increased perceptual abilities.<ref>{{cite journal | vauthors = Polley DB, Steinberg EE, Merzenich MM | title = Perceptual learning directs auditory cortical map reorganization through top-down influences | journal = The Journal of Neuroscience | volume = 26 | issue = 18 | pages = 4970–82 | date = May 2006 | pmid = 16672673 | pmc = 6674159 | doi = 10.1523/JNEUROSCI.3771-05.2006 }}</ref> The tonotopic development of A1 in mouse pups is therefore an important factor in understanding the neurological basis of auditory learning.

Other species also show similar tonotopic development during critical periods. Rat tonotopic develop is nearly identical to mouse, but the critical period is shifted slightly earlier,<ref name=deVillers2007 /> and barn owls show an analogous auditory development in [[Interaural time difference|Interaural Time Differences]] (ITD).<ref>{{cite journal | vauthors = Knudsen EI |title=Capacity for Plasticity in the Adult Owl Auditory System Expanded by Juvenile Experience. |journal=Science |date=1998 |volume=279 |issue=5356 |pages=1531–1533 |doi=10.1126/SCIENCE.279.5356.1531|pmid=9488651 |bibcode=1998Sci...279.1531K }}</ref>

==== Plasticity of auditory critical period ====
The auditory critical period of rats, which lasts from postnatal day 11 (P11) to P13<ref name=deVillers2007 /> can be extended through deprivation experiments such as white noise-rearing.<ref name=Chang2003>{{
cite journal | vauthors = Chang EF, Merzenich MM | title = Environmental noise retards auditory cortical development | journal = Science | volume = 300 | issue = 5618 | pages = 498–502 | date = April 2003 | pmid = 12702879 | doi = 10.1126/SCIENCE.1082163 | bibcode = 2003Sci...300..498C | s2cid = 7912796 }}</ref> It has been shown that subsets of the tonotopic map in A1 can be held in a plastic state indefinitely by exposing the rats to white noise consisting of frequencies within a particular range determined by the experimenter.<ref name=Barkat2011 /><ref name=deVillers2007 /> For example, exposing a rat during auditory critical period to white noise that includes tone frequencies between 7&nbsp;kHz and 10&nbsp;kHz will keep the corresponding neurons in a plastic state far past the typical critical period–one study has retained this plastic state until the rats were 90 days old.<ref name=Barkat2011 />
Recent studies have also found that release of the neurotransmitter norepinephrine is required for critical period plasticity in the auditory cortex, however intrinsic tonotopic patterning of the auditory cortical circuitry occurs independently from norepinephrine release.<ref>{{cite journal | vauthors = Shepard K, Liles L, Weinshenker D, Liu R | year = 2015 | title = Norepinephrine is necessary for experience-dependent plasticity in the developing mouse auditory cortex | journal = The Journal of Neuroscience | volume = 35 | issue = 6| pages = 2432–7 | doi = 10.1523/jneurosci.0532-14.2015 | pmid = 25673838 | pmc = 4323528 }}</ref>
A recent toxicity study showed that in-utero and postnatal exposure to polychlorinated biphenyl (PCB) altered overall primary auditory cortex (A1) organization, including tonotopy and A1 topography. Early PCB exposure also changed the balance of excitatory and inhibitory inputs, which altered the ability of the auditory cortex to plastically reorganize  after changes in the acoustic environment, thereby altering the critical period of auditory plasticity.<ref>{{cite journal | vauthors = Kenet T, Froemke RC, Schreiner CE, Pessah IN, Merzenich MM | year = 2007 | title = Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy, receptive fields, and plasticity in rat primary auditory cortex | journal = Proceedings of the National Academy of Sciences | volume = 104 | issue = 18| pages = 7646–7651 | doi = 10.1073/pnas.0701944104 | pmid = 17460041 | doi-access = free | pmc = 1855918 | bibcode = 2007PNAS..104.7646K }}</ref>

==== Adult plasticity ====

Studies in mature A1 have focused on neuromodulatory influences and have found that direct and indirect vagus nerve stimulation, which triggers neuromodulator release, promotes adult auditory plasticity.<ref>{{cite journal | vauthors = Engineer ND, Riley JR, Seale JD, Vrana WA, Shetake JA, Sudanagunta SP, Kilgard MP | year = 2011 | title = Reversing pathological neural activity using targeted plasticity | journal = Nature | volume = 470 | issue = 7332| pages = 101–4 | doi = 10.1038/nature09656 | pmid = 21228773 | pmc = 3295231 | bibcode = 2011Natur.470..101E }}</ref> Cholinergic signaling has been shown to engage 5-HT3AR cell activity across cortical areas and facilitate adult auditory plasticity.<ref>{{cite journal | vauthors = Takesian AE, Bogart LJ, Lichtman JW, Hensch TK | year = 2018 | title = Inhibitory circuit gating of auditory critical-period plasticity | journal = Nature Neuroscience | volume = 21 | issue = 2| pages = 218–227 | doi = 10.1038/s41593-017-0064-2 | pmid = 29358666 | pmc = 5978727 }}</ref> Furthermore, behavioral training using rewarding or aversive stimuli, commonly known to engage cholinergic afferents and 5-HT3AR cells, has also been shown to alter and shift adult tonotopic maps.<ref>{{cite journal | vauthors = Polley D, Steinberg E, Merzenich M | year = 2006 | title = Perceptual learning directs auditory cortical map reorganization through top-down influences | journal = The Journal of Neuroscience | volume = 26 | issue = 18| pages = 4970–4982 | doi = 10.1523/jneurosci.3771-05.2006 | pmid = 16672673 | doi-access = free | pmc = 6674159 }}</ref>