Learning to Encode Timing: Mechanisms of Plasticity in the Auditory Brainstem

Learning to Encode Timing: Mechanisms of Plasticity in the Auditory Brainstem Thanos Tzounopoulos Nina Kraus

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Learning to Encode Timing: Mechanisms of Plasticity in the Auditory Brainstem 2009 Neuron 10.1016/j.neuron.2009.05.002 unknown2009-learning-to-encode-timing-mechanisms-of-plas unknown2009-learning-to-encode-timing-mechanisms-of-plas.txt, the project's staged copy 36ea54226e2a1ea881e1d6d6bfbc36edae5d5cca not-redistributable neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them whether the auditory brainstem, long treated as a hard-wired relay optimised for timing, is a site of experience-dependent plasticity Quotation withheld because this record is not cleared for redistribution. does the mammalian auditory brainstem express the cellular mechanisms that could support the learning effects seen in humans Quotation withheld because this record is not cleared for redistribution. assembles slice physiology and human evoked-potential evidence to overturn the view that early auditory processing is non-plastic, and identifies cell-specific synaptic and intrinsic plasticity in brainstem nuclei Quotation withheld because this record is not cleared for redistribution. existence Quotation withheld because this record is not cleared for redistribution. auditory brainstem plasticity Quotation withheld because this record is not cleared for redistribution. review review Quotation withheld because this record is not cleared for redistribution. mechanisms Synapse-specific plasticity simultaneously disinhibits fusiform cells and strengthens their excitatory input, driving the fusiform hyperactivity that underlies tinnitus Quotation withheld because this record is not cleared for redistribution. mechanisms Anti-Hebbian STDP reweights parallel-fiber synapses so that inputs predicting incoming sensory activity are weakened, building a 'negative image' that cancels the sensory consequences of the animal's own movements Quotation withheld because this record is not cleared for redistribution. mechanisms Nitric oxide diffusing out of MNTB principal neurons suppresses postsynaptic Kv3 channels in neighbouring cells, providing intercellular gain control during loud sound Quotation withheld because this record is not cleared for redistribution. mechanisms Corticofugal (efferent) feedback from higher-order processing levels descends onto brainstem nuclei and is the route by which language and musical experience alter subcortical timing Quotation withheld because this record is not cleared for redistribution. the field inferred incapacity from function - a structure optimised for fast reliable signalling was assumed to be ill-suited to plasticity, and the test was not run Quotation withheld because this record is not cleared for redistribution. and effort was directed to the cortex instead, which is where the plasticity literature accumulated Quotation withheld because this record is not cleared for redistribution. the reversal is built from two independent lines that meet in the middle - slice physiology in animals and non-invasive evoked potentials in humans Quotation withheld because this record is not cleared for redistribution. adding an in-vivo-like feature to the standard slice preparation reversed a standing conclusion about the same nucleus Quotation withheld because this record is not cleared for redistribution. and the authors generalise the warning rather than confining it to that result Quotation withheld because this record is not cleared for redistribution. plasticity is shown to be feature-specific rather than a gain change, which is what makes it evidence of learning rather than of arousal Quotation withheld because this record is not cleared for redistribution. the functional interpretation of the dorsal cochlear nucleus is imported wholesale from the electrosensory lobe of a fish, where anti-Hebbian plasticity cancels self-generated input Quotation withheld because this record is not cleared for redistribution. the argument that the same job exists in audition is made by matching the problem, not the anatomy - both systems must separate external signals from self-generated ones Quotation withheld because this record is not cleared for redistribution. human timescales are stacked deliberately: lifelong language and musical experience, then training over weeks, then attention within a session Quotation withheld because this record is not cleared for redistribution. the same plasticity mechanisms are used to explain a pathology, which converts the review's claim into something testable in tinnitus Quotation withheld because this record is not cleared for redistribution. a theory built for visual cortex is extended below the cortex, and the extension is flagged as the authors' view rather than an established result Quotation withheld because this record is not cleared for redistribution. The synaptic-plasticity evidence base comes overwhelmingly from brain slices, which differ substantially from the intact brain. what this limits: every plasticity claim in the review: MOST STUDIES OF SYNAPTIC PLASTICITY IN THE AUDITORY BRAINSTEM HAVE BEEN PERFORMED IN BRAIN SLICES Quotation withheld because this record is not cleared for redistribution. How naturally occurring noise exposure would induce the plasticity proposed to underlie tinnitus is not established. what this limits: the tinnitus account specifically: it is obvious that ELECTRICAL STIMULATION OF PARALLEL FIBERS CAN INDUCE SYNAPTIC PLASTICITY, but how naturally occurring noise exposure would do so is not established Quotation withheld because this record is not cleared for redistribution. How brainstem pathways adapt to ongoing sensory activity and contribute to perception of environmental sound remains largely unknown. what this limits: what the brainstem literature covers: MUCH LESS IS KNOWN ABOUT HOW THESE PATHWAYS ADAPT TO ONGOING SENSORY ACTIVITY AND HOW THEY CONTRIBUTE TO THE PERCEPTION AND INTERPRETATION OF ENVIRONMENTAL SOUNDS, INCLUDING SPEECH Quotation withheld because this record is not cleared for redistribution. most of the plasticity evidence comes from slices, which differ from the intact brain in ways that have already changed one conclusion what this limits: the plasticity evidence base as a whole: Quotation withheld THIS EXPERIMENTAL APPROACH HAS SUBSTANTIAL DIFFERENCES FROM STUDYING INTACT BRAINS IN VIVO Quotation withheld because this record is not cleared for redistribution. how noise exposure would induce the plasticity proposed to cause tinnitus is not established duplicate of: limitations[1] · what this limits: the same scope as limitations[1] - how naturally occurring noise exposure would induce the plasticity proposed to underlie tinnitus is not established Quotation withheld because this record is not cleared for redistribution. the pathophysiology of tinnitus remains poorly understood despite its prevalence what this limits: any mechanistic claim about the disorder: DESPITE THE WIDE PREVALENCE OF TINNITUS, THE PATHOPHYSIOLOGY OF THE DISORDER IS POORLY UNDERSTOOD Quotation withheld because this record is not cleared for redistribution. whether the fish-derived cancellation function applies to the dorsal cochlear nucleus is posed as an open question, not answered what this limits: the transfer of the cancellation function from the fish circuit: A KEY QUESTION IS WHETHER ANTI-HEBBIAN PLASTICITY OBSERVED IN THE DCN CAN SERVE A SIMILAR FUNCTION Quotation withheld because this record is not cleared for redistribution. whether brainstem plasticity is driven top-down, locally, or by both is unresolved what this limits: the locus of control for brainstem plasticity: whether changes are INITIATED/MODULATED IN A TOP-DOWN FASHION ... OR THROUGH LOCAL MECHANISMS OF ADAPTATION is unresolved Quotation withheld because this record is not cleared for redistribution. how these pathways adapt and contribute to perception is much less understood than how they transmit timing duplicate of: limitations[2] · what this limits: the same scope as limitations[2] - transmission of timing is understood far better than adaptation or perception Quotation withheld because this record is not cleared for redistribution. The Reverse Hierarchy Theory, first formulated to describe top-down influence of higher visual cortical areas on lower ones, is taken over to explain top-down modulation of auditory processing and extended below cortex to the brainstem. Quotation withheld because this record is not cleared for redistribution. The adaptive-sensory-processor / 'negative image' account of anti-Hebbian STDP in the cerebellum-like electrosensory lobe is imported as a candidate functional model for the mammalian dorsal cochlear nucleus. Quotation withheld because this record is not cleared for redistribution. anti-Hebbian STDP building a negative image that cancels the sensory consequences of the animal's own movements, imported as the candidate function of the dorsal cochlear nucleus Quotation withheld because this record is not cleared for redistribution. the Reverse Hierarchy Theory, built for higher-to-lower visual cortical areas and extended here to corticofugal control of the brainstem Quotation withheld because this record is not cleared for redistribution. the parallel-fiber and climbing-fiber arrangement, used both as the structural analogy for the DCN and as the model for how auditory nerve activity might induce plasticity Quotation withheld because this record is not cleared for redistribution. auditory brainstem response auditory brainstem response Quotation withheld because this record is not cleared for redistribution. STDP - Hebbian at fusiform cells and anti-Hebbian at cartwheel cells; ONE induction protocol producing opposite signs, decided by cell type Quotation withheld because this record is not cleared for redistribution. the auditory brainstem - as a hard-wired relay optimised for timing versus as a plastic, experience-modified structure; the paper is the transition between the two readings Quotation withheld because this record is not cleared for redistribution. plasticity - synaptic (changed connection strength) versus intrinsic (changed excitability through ion channels); the review insists a circuit needs one or the other Quotation withheld because this record is not cleared for redistribution. experience effects - as a generalised gain change versus as feature-specific alteration; only the second counts as learning Quotation withheld because this record is not cleared for redistribution. the MNTB - as a simple faithful relay versus as a nucleus that fails under realistic activity; the reading depends on what the slice preparation includes Quotation withheld because this record is not cleared for redistribution. brainstem plasticity - as adaptive learning versus as the cause of a disease; the same mechanism read with opposite valence in tinnitus Quotation withheld because this record is not cleared for redistribution. claim_type: critique a second reading DIFFERING from the recorded value. Recorded: existence — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: narrative review pairing rodent brain-slice recordings of synaptic and intrinsic plasticity with non-invasive human auditory brainstem responses a second reading DIFFERING from the recorded value. Recorded: review — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. phenomenon: experience-dependent plasticity in subcortical auditory processing a second reading DIFFERING from the recorded value. Recorded: auditory brainstem plasticity — note: a second reading, verbatim-verified, disagreeing with the value on the record. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. extends → Reverse Hierarchy Theory (Ahissar and Hochstein, 2004) Quotation withheld because this record is not cleared for redistribution. contradicts → the traditional view that early sensory processing stages are hard-wired and non-plastic Quotation withheld because this record is not cleared for redistribution. critiques → the inference from specialisation for precise timing to incapacity for plasticity Quotation withheld because this record is not cleared for redistribution. contradicts → the treatment of the MNTB as a simple and faithful relay nucleus Quotation withheld because this record is not cleared for redistribution. builds-on → Krishnan and colleagues, who first showed that language experience alters brainstem pitch encoding Quotation withheld because this record is not cleared for redistribution. extends → the Reverse Hierarchy Theory, from intracortical feedback to subcortical processing Quotation withheld because this record is not cleared for redistribution. supports → the account of tinnitus as centrally maintained rather than purely cochlear Quotation withheld because this record is not cleared for redistribution. Hebbian —contrasted-with→ anti-Hebbian Hebbian anti-Hebbian strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. fusiform —contrasted-with→ cartwheel cells fusiform cartwheel cells strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. RETRACTED (WRONG TYPE: a KIND, not a PART) · intrinsic plasticity —is-a→ plasticity intrinsic plasticity plasticity RETRACTED: WRONG TYPE: a KIND, not a PART. Intrinsic plasticity is a sort of plasticity, not a component of it. — strength of the relation: 0.95 Quotation withheld because this record is not cleared for redistribution. frequency following response —part-of→ auditory brainstem response frequency following response auditory brainstem response strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span writes 'ABR'; endpoint abbreviated. Quotation withheld because this record is not cleared for redistribution. plasticity —causes→ tinnitus plasticity tinnitus strength of the relation: 0.75 Audit 2026-09-28: DOUBTFUL - read against its span and kept, but plasticity-driven disinhibition is linked to tinnitus; causes is loose. Quotation withheld because this record is not cleared for redistribution. dorsal cochlear nucleus —part-of→ auditory brainstem dorsal cochlear nucleus auditory brainstem strength of the relation: 0.95 Quotation withheld because this record is not cleared for redistribution. standard error of the mean standard error of the mean Quotation withheld because this record is not cleared for redistribution. fast Fourier transform fast Fourier transform Quotation withheld because this record is not cleared for redistribution. phase locking phase locking Quotation withheld because this record is not cleared for redistribution. Contrary to the traditional view that early sensory stages are not plastic, the auditory brainstem is dynamic. Quotation withheld because this record is not cleared for redistribution. In the dorsal cochlear nucleus one protocol produces LTP in fusiform cells and LTD in cartwheel cells. Quotation withheld because this record is not cleared for redistribution. Language experience reshapes brainstem coding: speakers of tonal languages show enhanced neural representation of pitch. Quotation withheld because this record is not cleared for redistribution. Experience-driven changes in the brainstem are selective to particular stimulus features rather than an across-the-board amplification of all responses. Quotation withheld because this record is not cleared for redistribution. Acoustic environment tunes intrinsic excitability: in quiet conditions PKC phosphorylation of Kv3.1b potassium channels lowers the potassium current so that neurons fire only at low frequencies. Quotation withheld because this record is not cleared for redistribution. The medial nucleus of the trapezoid body is not a faithful relay: under in-vivo-like spontaneous activity it fails to entrain reliably to prolonged high-frequency stimuli because of short-term plasticity, even though it still encodes stimulus onset precisely. Quotation withheld because this record is not cleared for redistribution. The authors argue that the Reverse Hierarchy Theory, formulated for cortex, extends to subcortical processing and may itself initiate or modulate brainstem plasticity. Quotation withheld because this record is not cleared for redistribution. one induction protocol produces LTP in fusiform cells and LTD in cartwheel cells Quotation withheld because this record is not cleared for redistribution. speakers of tonal languages have enhanced neural representation of pitch in the brainstem Quotation withheld because this record is not cleared for redistribution. musical experience produces more robust brainstem encoding of speech, linguistic pitch patterns and vocal emotion Quotation withheld because this record is not cleared for redistribution. brainstem encoding is disrupted in subsets of poor readers and children with autism Quotation withheld because this record is not cleared for redistribution. brainstem responses are affected by attention and are larger to a speech syllable than to its time-reversed version Quotation withheld because this record is not cleared for redistribution. experience does not produce a generalised gain change but alters specific stimulus features Quotation withheld because this record is not cleared for redistribution. brainstem processing can also be changed by auditory training over weeks, not only by lifelong experience Quotation withheld because this record is not cleared for redistribution. adding in-vivo-like spontaneous activity to MNTB slices revealed synaptic failures at high frequency that earlier studies had not seen Quotation withheld because this record is not cleared for redistribution. so the MNTB is not a simple faithful relay and may not entrain reliably to sustained high-frequency input Quotation withheld because this record is not cleared for redistribution. phosphorylation state of Kv3.1b channels sets whether neurons fire at low or high frequency, tracking the acoustic environment Quotation withheld because this record is not cleared for redistribution. activity in one MNTB neuron can modulate the excitability of its neighbours, a candidate gain reduction in loud noise Quotation withheld because this record is not cleared for redistribution. retrograde GABA signalling in the lateral superior olive adjusts the excitation-inhibition balance underlying sound localisation Quotation withheld because this record is not cleared for redistribution. synapse-specific plasticity that disinhibits and excites fusiform cells can produce hyperactivity like that seen in animals with behavioural signs of tinnitus Quotation withheld because this record is not cleared for redistribution. cortical activation shapes the tuning of cochlear nucleus neurons, giving a route for top-down control Quotation withheld because this record is not cleared for redistribution. intrinsic plasticity intrinsic plasticity Quotation withheld because this record is not cleared for redistribution. spike-timing-dependent plasticity (STDP) spike-timing-dependent plasticity (STDP) Quotation withheld because this record is not cleared for redistribution. auditory brainstem response (ABR) auditory brainstem response (ABR) Quotation withheld because this record is not cleared for redistribution. frequency following response (FFR) frequency following response (FFR) Quotation withheld because this record is not cleared for redistribution. tinnitus tinnitus Quotation withheld because this record is not cleared for redistribution. pitch tracking pitch tracking Quotation withheld because this record is not cleared for redistribution. Reverse Hierarchy Theory (RHT) Reverse Hierarchy Theory (RHT) Quotation withheld because this record is not cleared for redistribution. auditory brainstem response auditory brainstem response Quotation withheld because this record is not cleared for redistribution. frequency following response frequency following response Quotation withheld because this record is not cleared for redistribution. spike-timing-dependent plasticity spike-timing-dependent plasticity Quotation withheld because this record is not cleared for redistribution. intrinsic plasticity intrinsic plasticity Quotation withheld because this record is not cleared for redistribution. Tinnitus Tinnitus Quotation withheld because this record is not cleared for redistribution. Reverse Hierarchy Theory Reverse Hierarchy Theory Quotation withheld because this record is not cleared for redistribution. <4000 Hz — Upper frequency limit of the 'low-frequency' sounds that the binaural timing circuitry of the mammalian brainstem is specialised to localise Quotation withheld because this record is not cleared for redistribution. 4–12 µm — Diameter of the myelinated globular-bushy-cell axons giving rise to the calyx of Held, large enough to give fast conduction velocity Quotation withheld because this record is not cleared for redistribution. 200 µs — Delay with which inhibitory input reaches the cat lateral superior olive after the excitatory input Quotation withheld because this record is not cleared for redistribution. 40 ms time bins, 1 ms interval — Window length and step of the running short-term Fourier analysis used to extract pitch contours from the brainstem response Quotation withheld because this record is not cleared for redistribution. 0.5 ms — Scale of the x-axis tick marks in Figure 1, indicating that the experience-related timing disruptions and enhancements are of the order of tenths of a millisecond Quotation withheld because this record is not cleared for redistribution. <4000 Hz — the low-frequency range localised by interaural timing in mammals Quotation withheld because this record is not cleared for redistribution. microsecond range — the interaural phase differences the brainstem resolves Quotation withheld because this record is not cleared for redistribution. last 10 years — the period over which brainstem timing mechanisms were worked out Quotation withheld because this record is not cleared for redistribution. relative timing of presynaptic and postsynaptic action potentials relative timing of presynaptic and postsynaptic action potentials Quotation withheld because this record is not cleared for redistribution. sound intensity sound intensity Quotation withheld because this record is not cleared for redistribution. pitch tracking pitch tracking Quotation withheld because this record is not cleared for redistribution.

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