Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus

Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus Ono Bishop Oliver

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Neuronal sensitivity to the interaural time difference of the sound envelope in the mouse inferior colliculus 2020 Hearing Research 10.1016/j.heares.2019.107844 Ono2020-neuronal-sensitivity-to-the-interaural-time Ono2020-neuronal-sensitivity-to-the-interaural-time.txt, the project's staged copy 77c97a7dd0999dab5da6bf9196f5a618259061e1 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 neurons in the mouse midbrain are sensitive to a binaural timing cue the animal is thought unable to use Quotation withheld because this record is not cleared for redistribution. how neurons respond to interaural time differences carried in the envelope of amplitude-modulated sound, in a small mammal Quotation withheld because this record is not cleared for redistribution. the circuitry to process interaural time differences persists in the mouse despite its lack of low-frequency hearing, and is probably shaped in the lateral superior olive Quotation withheld because this record is not cleared for redistribution. existence Quotation withheld because this record is not cleared for redistribution. envelope interaural time difference sensitivity in inferior colliculus neurons Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms ITD tuning is inherited from brainstem (chiefly LSO) inputs rather than computed within the inferior colliculus, because IC phase-locking to monaural sound degrades at the modulation rates where ITD sensitivity persists Quotation withheld because this record is not cleared for redistribution. mechanisms The enlarged LSO, not the small MSO, supplies the mouse IC with its ITD sensitivity Quotation withheld because this record is not cleared for redistribution. mechanisms The contralateral-leading preference arises because LSO projections crossing to the opposite IC are purely excitatory while the ipsilateral ones mix excitation and inhibition Quotation withheld because this record is not cleared for redistribution. mechanisms Trough-type tuning is produced by coincidence of excitatory input from one ear with inhibitory input from the other Quotation withheld because this record is not cleared for redistribution. the sensitivity is probably not built in the midbrain but inherited from the brainstem Quotation withheld because this record is not cleared for redistribution. the lateral superior olive is much larger than the medial superior olive in the mouse, which is the argument for it being the source Quotation withheld because this record is not cleared for redistribution. contralateral projections from the lateral superior olive are exclusively excitatory while ipsilateral ones are mixed, which would explain why firing rises when the contralateral sound leads Quotation withheld because this record is not cleared for redistribution. GABAergic cells may not carry the timing information themselves but could sharpen tuning downstream by raising conductance Quotation withheld because this record is not cleared for redistribution. lateral superior olive neurons in gerbil change firing probability over microseconds, so even a small mammal with an undeveloped medial superior olive could detect these differences Quotation withheld because this record is not cleared for redistribution. Only a limited stimulus set was tested, so the reported proportion of ITD-sensitive neurons may be an underestimate. what this limits: the reported proportion of ITD-sensitive neurons, with the direction named: EVEN MORE NEURONS ... MIGHT TURN OUT TO BE SENSITIVE ... IF THEY ARE TESTED WITH MORE DIVERSE SOUND STIMULI THAN THOSE USED IN THE PRESENT STUDY Quotation withheld because this record is not cleared for redistribution. Best and characteristic frequency could not be determined for two glutamatergic cells. what this limits: the frequency-tuning analysis: IN TWO GLUTAMATERGIC NEURONS, WE COULD NOT IDENTIFY EITHER BF OR CF BECAUSE THEIR RESPONSIVENESS TO TONES WAS TOO LOW Quotation withheld because this record is not cleared for redistribution. The raised-sine stimulus broadens the carrier spectrum, which could itself affect measured ITD sensitivity. what this limits: every ITD sensitivity measured with the raised sine: THE BROADENING OF THE SPECTRUM IN THE RAISED SINE STIMULI MIGHT AFFECT THE ITD SENSITIVITY IN THE IC NEURONS Quotation withheld because this record is not cleared for redistribution. the neuronal mechanism behind the dependence on envelope shape is stated to be unknown what this limits: any mechanistic reading of the envelope-shape effect: IT IS UNCLEAR WHAT NEURONAL MECHANISM UNDERLIES THIS SENSITIVITY TO THE ENVELOPE SHAPE Quotation withheld because this record is not cleared for redistribution. more neurons might prove sensitive if tested with a wider range of stimuli than were used here duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - the proportion is a lower bound set by the stimulus set Quotation withheld because this record is not cleared for redistribution. the spectral-broadening artefact of the raised sine stimulus is bounded at under 10 percent, but the supporting measurement is not shown what this limits: the same scope as limitations[2], and the control that retires it is not printed: THE BROADENING ... WAS LESS THAN 10% ... (DATA NOT SHOWN). SO, THE EFFECT OF THE SPECTRUM CHANGE IS LIKELY TO BE LIMITED Quotation withheld because this record is not cleared for redistribution. recordings were dropped when the recording depth and the labelled site did not clearly correspond what this limits: the anatomical assignment of the recordings: WE EXCLUDED THE DATA WHEN THE CORRESPONDENCE BETWEEN THE RECORDING DEPTH AND THE LABELED SITE WAS AMBIGUOUS Quotation withheld because this record is not cleared for redistribution. the change in firing rate within the mouse's own physiological range was very small, so the authors conclude the cue may have minimal effect what this limits: the functional significance of the effect, as against its existence: THE CHANGE IN FIRING RATE WITHIN PHYSIOLOGICAL ITD RANGE WAS VERY SMALL IN MOST NEURONS. SO, THE ITD MAY HAVE MINIMAL EFFECTS ON THE FIRING RATE OF THE IC NEURONS Quotation withheld because this record is not cleared for redistribution. the raised-sine envelope, imported because a listener's threshold is lower for it than for a sinusoid Quotation withheld because this record is not cleared for redistribution. CP as an index of alignment, where 0 means the ITD curves are aligned near their peaks and 0.5 near their troughs Quotation withheld because this record is not cleared for redistribution. neurons whose responses were not tested at all five modulation frequencies excluded when the PERCENTAGE of beat-sensitive neurons was measured, while still included in the other beat sensitivity analyses eliminates: an inflated denominator - a neuron counts as not beat-sensitive when it was simply never tested at the frequency that would have shown it · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. ITD here means the delay between the ENVELOPES, not between the fine structures - the stimulus is built so the carrier has no interaural phase difference at all, which is what makes the claim possible in a high-frequency animal Quotation withheld because this record is not cleared for redistribution. GABAergic here means a cell the light drove, and glutamatergic a cell the light suppressed by more than 50 percent - a class defined by a response threshold, validated separately against GAD67 staining Quotation withheld because this record is not cleared for redistribution. CP is an index whose two values ARE the two hypotheses: 0 means the curves align at peaks, 0.5 means they align at troughs, so the measurement returns the answer directly rather than a test statistic Quotation withheld because this record is not cleared for redistribution. the physiological ITD range of the mouse is a derived quantity, from head size, and it is what makes every result here a claim about a cue the animal may never encounter Quotation withheld because this record is not cleared for redistribution. an animal is included only if its auditory brainstem response threshold is under 40 dB - hearing is an inclusion criterion with a number, not an assumption Quotation withheld because this record is not cleared for redistribution. claim_type: existence a second reading reaching the same value. Recorded: existence — note: a second reading reaching the same value from a different sentence. Not applied - a person decides. Quotation withheld because this record is not cleared for redistribution. method: extracellular single-unit recording with optogenetic identification of GABAergic cells, binaural beat amplitude-modulated noise, and phase-plot analysis a second reading DIFFERING from the recorded value. Recorded: electrophysiology — 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: over half of inferior colliculus neurons, of both cell types, synchronise to the beat between two differently modulated envelopes a second reading DIFFERING from the recorded value. Recorded: envelope interaural time difference sensitivity in inferior colliculus neurons — 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. builds-on → Ono et al., 2016; Ono et al., 2017 (optogenetic cell-type identification in IC) Quotation withheld because this record is not cleared for redistribution. extends → Ono et al., 2017 (pure-tone response properties of IC cell types) Quotation withheld because this record is not cleared for redistribution. builds-on → Batra et al., 1997c; Joris et al., 1995 (LSO envelope-ITD sensitivity in cat and rabbit) Quotation withheld because this record is not cleared for redistribution. builds-on → Bernstein et al., 1985 (human psychophysics of envelope ITD) Quotation withheld because this record is not cleared for redistribution. extends → reports that envelope interaural time differences are detected in the lateral superior olive of cat and rabbit Quotation withheld because this record is not cleared for redistribution. qualifies → the behavioural finding that mice cannot use interaural time differences in low-frequency sound to localise Quotation withheld because this record is not cleared for redistribution. supports → the proposal that a vestigial binaural circuit can persist in an animal that no longer uses it, as discussed for the Mexican free-tailed bat Quotation withheld because this record is not cleared for redistribution. confirms → psychophysical observations that a large envelope ITD is needed to shift the intracranial image away from the midline Quotation withheld because this record is not cleared for redistribution. builds-on → the peak-type and trough-type classification of ITD sensitivity established in the rabbit inferior colliculus Quotation withheld because this record is not cleared for redistribution. ITD —contrasted-with→ ILD ITD ILD strength of the relation: 1 · note: CRITERION: head size. A small head gives a small ITD range, so small animals are held to use level differences instead - which is the assumption this paper tests against Quotation withheld because this record is not cleared for redistribution. LSO —contrasted-with→ MSO LSO MSO strength of the relation: 1 · note: CRITERION: relative size. The argument for the source is anatomical, not physiological - the LSO is much larger in this animal Quotation withheld because this record is not cleared for redistribution. LSO —causes→ IC LSO IC strength of the relation: 0.9 · note: an inference from anatomy and from cat and rabbit recordings, not measured here Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but ITD sensitivity in the IC is 'MOST LIKELY due to' inputs from the LSO; causes is hedged and 'IC' as the target drops the ITD sensitivity. Quotation withheld because this record is not cleared for redistribution. lateral lemniscus —causes→ IC lateral lemniscus IC strength of the relation: 0.6 — the record marks this weak · note: a second candidate source, raised and left open Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the lateral lemniscus 'MAY contribute' to binaural processing in the IC; causes is hedged. Quotation withheld because this record is not cleared for redistribution. ICC —part-of→ IC ICC IC strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. GABAergic —contrasted-with→ glutamatergic GABAergic glutamatergic status: the paper's own words: is not known · strength of the relation: 1 · note: 25 percent against 75 percent, and the paper's question is whether the two differ in this function Quotation withheld because this record is not cleared for redistribution. trough-type —contrasted-with→ peak-type trough-type peak-type strength of the relation: 1 · note: the two established alternatives, imported from the rabbit Quotation withheld because this record is not cleared for redistribution. CD —operationalised-as→ ITD CD ITD strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. vector strength —operationalised-as→ ITD vector strength ITD strength of the relation: 1 · note: computed twice per cell - to the beat and to the contralateral modulation - and it is the COMPARISON between the two that kills the local account Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but vector strength quantified PHASE LOCKING of ITD-sensitive neurons; operationalised-as ITD is loose. Quotation withheld because this record is not cleared for redistribution. ILD —causes→ IC ILD IC strength of the relation: 0.8 · note: SAME SIGN AS THE ITD EFFECT: both cues raise firing when the contralateral side leads or is louder, so they would add Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but in the IC the ILD also evokes a higher firing rate for a louder contralateral sound; 'causes IC' is loose. Quotation withheld because this record is not cleared for redistribution. raised sine —contrasted-with→ SAM raised sine SAM strength of the relation: 1 · note: steeper envelope, more spectral sidebands - which is why the spectral artefact had to be bounded Quotation withheld because this record is not cleared for redistribution. rMTF —operationalised-as→ modulation frequency rMTF modulation frequency strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the rMTF was MEASURED to evaluate firing-rate change with modulation frequency; operationalised-as is loose. Quotation withheld because this record is not cleared for redistribution. Rayleigh test Rayleigh test Quotation withheld because this record is not cleared for redistribution. Fisher's exact test Fisher's exact test Quotation withheld because this record is not cleared for redistribution. Wilcoxon signed-rank test Wilcoxon signed-rank test Quotation withheld because this record is not cleared for redistribution. ANOVA ANOVA Quotation withheld because this record is not cleared for redistribution. post hoc multiple comparison test post hoc multiple comparison test Quotation withheld because this record is not cleared for redistribution. regression regression Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. vector strength (circular phase-locking measure) vector strength (circular phase-locking measure) Quotation withheld because this record is not cleared for redistribution. Rayleigh test Rayleigh test Quotation withheld because this record is not cleared for redistribution. paired Wilcoxon signed-rank test paired Wilcoxon signed-rank test Quotation withheld because this record is not cleared for redistribution. Two-way ANOVA test Two-way ANOVA test Quotation withheld because this record is not cleared for redistribution. vector strength vector strength Quotation withheld because this record is not cleared for redistribution. More than half of both inhibitory and excitatory inferior colliculus neurons in the mouse locked their firing to the binaural beat carried in the sound envelope, i.e. they were envelope-ITD sensitive. Quotation withheld because this record is not cleared for redistribution. To the authors' knowledge, envelope-ITD sensitivity had not been shown in the mouse auditory pathway before. Quotation withheld because this record is not cleared for redistribution. The proportion of ITD-sensitive neurons did not differ between glutamatergic and GABAergic cells. Quotation withheld because this record is not cleared for redistribution. Characteristic delay coincided with the trough rather than the peak of the ITD curve in most cells, identifying them as trough-type. Quotation withheld because this record is not cleared for redistribution. Within the mouse's physiological ITD range the ITD curve slopes positively toward the contralateral side for both cell types, so firing is higher when the contralateral envelope leads. Quotation withheld because this record is not cleared for redistribution. Above 256 Hz modulation, phase-locking to the binaural beat exceeded phase-locking to the monaural contralateral stimulus in most responses. Quotation withheld because this record is not cleared for redistribution. Rate modulation transfer functions of most IC neurons of both types fell into the low-rate, low-pass or band-reject classes for sinusoidal modulation. Quotation withheld because this record is not cleared for redistribution. Glutamatergic neurons synchronized to the beat fired faster than unsynchronized neurons of either type at 64 Hz modulation. Quotation withheld because this record is not cleared for redistribution. The slope of the ITD curve near zero did not differ between GABAergic and glutamatergic neurons. Quotation withheld because this record is not cleared for redistribution. more than half of both GABAergic and glutamatergic neurons synchronised to the binaural beat frequency in the envelopes Quotation withheld because this record is not cleared for redistribution. 47 neurons were recorded, 18 GABAergic and 29 glutamatergic Quotation withheld because this record is not cleared for redistribution. characteristic phase was close to 0.5 in both cell types, which is the trough-type pattern Quotation withheld because this record is not cleared for redistribution. the squared deviation from the unity line was significantly smaller for mean trough time than mean peak time, 0.87 against 6.62 ms squared Quotation withheld because this record is not cleared for redistribution. within the physiological ITD range the slope was positive toward the contralateral side, whatever the cell type or stimulus Quotation withheld because this record is not cleared for redistribution. the firing pattern shaped by envelope ITD matches that of level differences, which also favour the contralateral side in these neurons Quotation withheld because this record is not cleared for redistribution. VS contra was larger than VS beat when the modulation frequency was lower than 128 Hz, and smaller than VS beat when it was higher than 256 Hz Quotation withheld because this record is not cleared for redistribution. THE LOCAL MECHANISM EXCLUDED BY THE PAPER'S OWN DATA: sensitivity at high modulation frequency is not likely to be shaped by coincidence detection in the IC Quotation withheld because this record is not cleared for redistribution. THE INGREDIENT IS WORSE THAN THE PRODUCT: a local mechanism needs highly phase-locked monaural inputs, and monaural phase-locking degrades where the sensitivity persists Quotation withheld because this record is not cleared for redistribution. so the sensitivity is more likely inherited from brainstem neurons than built in the midbrain Quotation withheld because this record is not cleared for redistribution. ARTEFACT BOUNDED RATHER THAN ASSUMED AWAY: the raised sine broadens the spectrum by less than 10 percent even at 512 Hz, so its effect is judged limited Quotation withheld because this record is not cleared for redistribution. NULL BETWEEN CELL TYPES: the percentages synchronised did not differ significantly between glutamatergic and GABAergic neurons Quotation withheld because this record is not cleared for redistribution. NULL AGAIN: fewer GABAergic than glutamatergic neurons synchronised to the raised sine, and that difference was not significant either Quotation withheld because this record is not cleared for redistribution. the ITD slope was neither significantly different between envelope shapes nor between cell types Quotation withheld because this record is not cleared for redistribution. THE AUTHORS DEFLATE THEIR OWN RESULT: the firing-rate change within the physiological range was very small, so the cue may have minimal effect on these neurons Quotation withheld because this record is not cleared for redistribution. AND OFFER A VESTIGIAL READING: the sensitivity may belong to a circuit mice no longer use for binaural hearing Quotation withheld because this record is not cleared for redistribution. the trough of the ITD curve covers most of the mouse's whole physiological range Quotation withheld because this record is not cleared for redistribution. the escape route offered is echoes: real environments would deliver longer delays than the head alone allows Quotation withheld because this record is not cleared for redistribution. humans detect these envelope differences well despite limited high-frequency hearing, which is the opposite asymmetry Quotation withheld because this record is not cleared for redistribution. the finding is stated as new for the mouse auditory pathway Quotation withheld because this record is not cleared for redistribution. sound envelope sound envelope Quotation withheld because this record is not cleared for redistribution. beat-sensitive neurons beat-sensitive neurons Quotation withheld because this record is not cleared for redistribution. best frequency (BF) best frequency (BF) Quotation withheld because this record is not cleared for redistribution. characteristic frequency (CF) characteristic frequency (CF) Quotation withheld because this record is not cleared for redistribution. characteristic phase (CP) characteristic phase (CP) Quotation withheld because this record is not cleared for redistribution. characteristic delay (CD) characteristic delay (CD) Quotation withheld because this record is not cleared for redistribution. envelope envelope Quotation withheld because this record is not cleared for redistribution. CP CP Quotation withheld because this record is not cleared for redistribution. CD CD Quotation withheld because this record is not cleared for redistribution. trough-type trough-type WHOSE RESULT THIS IS: Previous studies reported - THE SUBJECT OF THIS RESULT IS AN INDEFINITE STUDY, NOT THIS PAPER. 'Previous studies reported', 'studies in guinea pig showed', 'recent studies have reported' - somebody else's work under a common noun rather than a name, with a citation in the sentence and no first-person marker. The quote is verbatim and the claim is true; only the attribution is wrong. FOUND BY MEASURING MY OWN CUE'S RECALL: the first sweep required a NAMED author as the subject ('Sperling (1960) demonstrated') and found 17. Reading eleven citation-bearing findings on 'Plakke2016' by hand showed four the cue could not see - 'A study examining recognition found', 'studies of typical human subjects have demonstrated', 'A follow up study found' - so the named cue's 17 was a floor and not a count. A CUE'S FALSE POSITIVES TELL YOU NOTHING ABOUT ITS FALSE NEGATIVES, and the only way to find these was to read a record's whole layer. Quotation withheld because this record is not cleared for redistribution. vector strength vector strength Quotation withheld because this record is not cleared for redistribution. modulation envelope modulation envelope Quotation withheld because this record is not cleared for redistribution. phase locking of spike responses phase locking of spike responses Quotation withheld because this record is not cleared for redistribution. slope of the ITD curve around zero ITD slope of the ITD curve around zero ITD Quotation withheld because this record is not cleared for redistribution. SPL level SPL level Quotation withheld because this record is not cleared for redistribution. modulation frequency modulation frequency Quotation withheld because this record is not cleared for redistribution. ITD ITD Quotation withheld because this record is not cleared for redistribution. vector strength vector strength Quotation withheld because this record is not cleared for redistribution. 47 neurons, of which 18 were GABAergic and 29 were glutamatergic — sample of single units recorded with binaural beat AM sound Quotation withheld because this record is not cleared for redistribution. 30 — number of VGAT-ChR2 transgenic mice used Quotation withheld because this record is not cleared for redistribution. ± 50 μs — the physiological range of interaural time difference available to a mouse, set by head size Quotation withheld because this record is not cleared for redistribution. 75 % / 25% — proportion of glutamatergic versus GABAergic neurons making up the inferior colliculus Quotation withheld because this record is not cleared for redistribution. close to 0.5 — characteristic phase of both cell types, the value indicating trough-aligned ITD curves Quotation withheld because this record is not cleared for redistribution. left, 30.7 ± 1.1 dB, right, 30.3 ± 1.0 dB, n = 30 — auditory brainstem response thresholds confirming normal hearing in the recorded mice Quotation withheld because this record is not cleared for redistribution. p = 0.00545 — significance of the change in glutamatergic synchronization across modulation frequency (Fisher's exact test) Quotation withheld because this record is not cleared for redistribution. ±50 μs — the mouse's physiological ITD range, derived from head size Quotation withheld because this record is not cleared for redistribution. <4 kHz — the ceiling on auditory-nerve phase locking that rules out fine-structure ITD at high frequencies Quotation withheld because this record is not cleared for redistribution. 75 % and 25% — glutamatergic and GABAergic shares of inferior colliculus neurons Quotation withheld because this record is not cleared for redistribution. 47 neurons — the sample: 18 GABAergic, 29 glutamatergic Quotation withheld because this record is not cleared for redistribution. less than 40 dB — auditory brainstem response threshold required for an animal to be used Quotation withheld because this record is not cleared for redistribution. p = 0.0625 — cell-type comparison of synchronisation percentages, reported as not significant Quotation withheld because this record is not cleared for redistribution. p = 0.125 — the same comparison for the raised sine, also reported as not significant Quotation withheld because this record is not cleared for redistribution.

The full text of this article is not redistributable, so it is not included here. The evidence sentences are withheld with it; the tag layer and its grounding status remain. The article itself is at https://doi.org/10.1016/j.heares.2019.107844.