Tonotopic Organization of Vertical Cells in the Dorsal Cochlear Nucleus of the CBA/J Mouse

Tonotopic Organization of Vertical Cells in the Dorsal Cochlear Nucleus of the CBA/J Mouse Muniak Ryugo

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Tonotopic Organization of Vertical Cells in the Dorsal Cochlear Nucleus of the CBA/J Mouse 2014 The Journal of comparative neurology 10.1002/cne.23454 Muniak2014-tonotopic-organization-of-vertical-cells-in Muniak2014-tonotopic-organization-of-vertical-cells-in.txt, the project's staged copy e568c67bfed195d463ef126fe08da62dbe4fbd9f 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 the spatial arrangement of vertical cells in the dorsal cochlear nucleus with respect to frequency Quotation withheld because this record is not cleared for redistribution. whether vertical cells and their projections are tonotopically organised in the intact mammalian brain, which had been inferred but never directly shown Quotation withheld because this record is not cleared for redistribution. converts an inference drawn from indirect evidence into a direct quantitative demonstration in 3D, and shows the arrangement is aligned to auditory nerve innervation Quotation withheld because this record is not cleared for redistribution. existence Quotation withheld because this record is not cleared for redistribution. tonotopic organisation of dorsal cochlear nucleus vertical cells Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms Auditory-nerve input pattern sets each cochlear nucleus neuron's best frequency, so the cochleotopic auditory-nerve projection imposes tonotopy on vertical cells Quotation withheld because this record is not cleared for redistribution. mechanisms Vertical cell axons ramify locally inside an isofrequency slab, which is what makes their inhibition of pyramidal (type IV) cells fall at or near best frequency Quotation withheld because this record is not cleared for redistribution. mechanisms Frequency-specific inhibitory demand in the cochlear nucleus, set by the gains and spectral notches of the mouse ear transfer function, shapes how many vertical cells are found at each frequency Quotation withheld because this record is not cleared for redistribution. retrograde labelling from a physiologically characterised AVCN site gives every labelled DCN cell an inherited BF, since the injection site's BF is measured and the cell's is not Quotation withheld because this record is not cleared for redistribution. normalising every case into one 3D template lets cells from separate animals be merged into a single dataset Quotation withheld because this record is not cleared for redistribution. dendrites and local axons stay within an isofrequency sheet defined by the incoming auditory nerve fibres, so inhibition lands on matched frequencies Quotation withheld because this record is not cleared for redistribution. a disynaptic tuberculoventral pathway whose delay is set by conduction velocity plus one synapse, proposed for echo suppression Quotation withheld because this record is not cleared for redistribution. near-BF inhibition of type IV units follows from vertical cell axons ramifying inside a single isofrequency slab Quotation withheld because this record is not cleared for redistribution. glycinergic inhibition sharpens spike timing in bushy and T-stellate cells on different timescales Quotation withheld because this record is not cleared for redistribution. BF confirmed by an automated 4-octave sweep at 20 dB above threshold, sampled every 1/25 octave Quotation withheld because this record is not cleared for redistribution. Retrograde filling was incomplete, so cells could only be characterised from the soma and primary dendrites rather than the full dendritic arbor. what this limits: every morphological characterisation: OUR RETROGRADE FILLS WERE INSUFFICIENT TO REVEAL THE FULL DENDRITIC ARBORIZATION OF EACH NEURON, SO MORPHOLOGICAL CHARACTERIZATIONS HAD TO BE BASED PRIMARILY UPON THE SOMA AND PRIMARY PROCESSES Quotation withheld because this record is not cleared for redistribution. Injection size, a possible confound for the cell counts, could not be measured reliably. what this limits: any comparison of cell counts across injections: QUANTIFYING THE SIZE OF AN INJECTION SITE IS NOTORIOUSLY DIFFICULT DUE TO THE AMBIGUITY IN DETERMINING THE EDGE OF THE EFFECTIVE UPTAKE REGION Quotation withheld because this record is not cleared for redistribution. The functional role of vertical cells is not settled by these anatomical results and needs further data. what this limits: any functional claim about vertical cells: MORE DATA ARE NEEDED TO BETTER UNDERSTAND THE FUNCTION OF THESE NEURONS Quotation withheld because this record is not cleared for redistribution. the size of an injection site cannot be quantified because the edge of the effective uptake region is ambiguous what this limits: the same scope as limitations[1] - injection size is not reliably quantifiable Quotation withheld because this record is not cleared for redistribution. apparent injection size is further distorted by photobleaching and exposure time what this limits: the apparent injection size specifically: THE APPARENT SIZE OF A FLUORESCENT INJECTION SITE IS SUBJECT TO THE EFFECTS OF PHOTOBLEACHING AND EXPOSURE TIME WHEN COLLECTING IMAGES Quotation withheld because this record is not cleared for redistribution. retrograde fills were incomplete, so morphology had to be judged from soma and primary processes alone duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - soma and primary processes only Quotation withheld because this record is not cleared for redistribution. some cells labelled at the wrong end of the frequency axis are attributed to axons of passage, an artifact of the tracer method what this limits: the low-frequency cells found after high-BF injections: THIS RESULT IS LIKELY DUE TO THE LABELING OF AXONS OF PASSAGE Quotation withheld because this record is not cleared for redistribution. the excess of low-BF cells is left explicitly unexplained rather than resolved what this limits: the low-BF labelling asymmetry, quantified and left open: LOW BF INJECTIONS TENDED TO LABEL MORE VERTICAL CELLS THAN HIGH BF INJECTIONS (R2 = 0.32, P < 0.003), THOUGH THE REASON FOR THIS TONOTOPIC FEATURE IS UNCLEAR Quotation withheld because this record is not cleared for redistribution. the function of these neurons is still open; the anatomy does not settle it duplicate of: limitations[2] · what this limits: the same scope as limitations[2] - the anatomy does not settle the function Quotation withheld because this record is not cleared for redistribution. 21 mice, 19 of them female, with no analysis by sex what this limits: any sex-general reading of the results: TWENTY-ONE ADULT CBA/J MICE (2 MALE, 19 FEMALE), with no analysis by sex Quotation withheld because this record is not cleared for redistribution. image levels and colour were adjusted per case, defended on the ground that the analysis used position and not luminance what this limits: the image-based measurements: LEVEL ADJUSTMENTS AND COLOR ENHANCEMENTS WERE APPLIED TO BRING OUT WEAK SIGNALS, defended because OUR ANALYSIS FOCUSED ON THE LOCATION OF LABELED PIXELS rather than their intensity Quotation withheld because this record is not cleared for redistribution. a frequency model built from AN innervation by cochlear origin, imported as an external criterion against which cell positions are predicted Quotation withheld because this record is not cleared for redistribution. the pinna transfer function and the frequency range of spectral notches, used to explain an anatomical cell-count gradient Quotation withheld because this record is not cleared for redistribution. the tonotopic finding corroborated by independently constructing a three-dimensional surface of the deep layer eliminates: a pattern that exists only in the projection or sectioning used to find it - the 3D reconstruction is built from the same tissue by a different route · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. type II electrophysiological response type II electrophysiological response Quotation withheld because this record is not cleared for redistribution. tonotopic and cochleotopic are used here as TWO DIFFERENT organisations that are compared - the arrangement of cell BFs versus the arrangement of auditory nerve input by cochlear origin; their alignment is the paper's result, so the terms cannot be synonyms in this paper Quotation withheld because this record is not cleared for redistribution. BF, for a vertical cell, is not measured at that cell; it is inherited from the physiologically characterised AVCN injection site that labelled it Quotation withheld because this record is not cleared for redistribution. type II names a response category, used throughout as a proxy for a cell class on the strength of a presumed identification Quotation withheld because this record is not cleared for redistribution. vertical names the dendritic orientation, not the cell's position - the arbors follow the perpendicular axis through the layered DCN Quotation withheld because this record is not cleared for redistribution. isofrequency sheet or slab - a plane of cells sharing a frequency, the unit in which this circuit is organised Quotation withheld because this record is not cleared for redistribution. method: physiologically targeted retrograde tracer injections in AVCN, cells reconstructed and normalised into a shared 3D template of the cochlear nucleus, then assessed by PCA, multiple regression and comparison to an independent frequency model 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: tonotopy in a brainstem interneuron population a second reading DIFFERING from the recorded value. Recorded: tonotopic organisation of dorsal cochlear nucleus vertical cells — 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 → Muniak et al., 2013 (normalised 3D template and quantitative frequency model of the mouse cochlear nucleus) Quotation withheld because this record is not cleared for redistribution. replicates → Lorente de Nó (1981) and subsequent morphological descriptions of vertical cells (Webster and Trune, 1982; Saint Marie et al., 1991; Zhang and Oertel, 1993; Rhode, 1999) Quotation withheld because this record is not cleared for redistribution. converts-to-direct-evidence → the standing inference from physiology and slice anatomy that vertical cells are tonotopically organised Quotation withheld because this record is not cleared for redistribution. supports → Wickesberg and Oertel: on-BF inhibition of bushy and stellate cells in AVCN Quotation withheld because this record is not cleared for redistribution. supports → Muniak et al. 2013: the AN-derived frequency model of the cochlear nucleus Quotation withheld because this record is not cleared for redistribution. qualifies → reports restricting vertical cells to the lower half of the deep layer Quotation withheld because this record is not cleared for redistribution. supports → Spirou et al.: cells sharing a frequency in the DCN are organised into slabs Quotation withheld because this record is not cleared for redistribution. extends → Lorente de No's morphological account of vertical cells Quotation withheld because this record is not cleared for redistribution. vertical cells —same-as→ tuberculoventral cells vertical cells tuberculoventral cells strength of the relation: 1 · note: alternate names in one clause, unhedged Quotation withheld because this record is not cleared for redistribution. vertical cells —part-of→ DCN vertical cells DCN strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. vertical cells —causes→ type II electrophysiological response vertical cells type II electrophysiological response strength of the relation: 0.8 · note: presumed source of - an identification the field treats as settled but the paper hedges; causes rather than same-as because a cell is not a response Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but vertical cells are the 'PRESUMED source' of the type II response; causes is hedged. Quotation withheld because this record is not cleared for redistribution. type II electrophysiological response —causes→ type IV response type II electrophysiological response type IV response strength of the relation: 0.75 · note: partially shaping; the weight carries the partially Quotation withheld because this record is not cleared for redistribution. BF —operationalised-as→ automated tuning curve protocol BF automated tuning curve protocol strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. tonotopic organization —operationalised-as→ principal component analysis tonotopic organization principal component analysis strength of the relation: 0.9 · note: one of four independent operationalisations of the same claim in this paper Quotation withheld because this record is not cleared for redistribution. tonotopic organization —operationalised-as→ multiple regression analysis tonotopic organization multiple regression analysis strength of the relation: 0.9 Quotation withheld because this record is not cleared for redistribution. principal component analysis principal component analysis Quotation withheld because this record is not cleared for redistribution. multiple regression multiple regression Quotation withheld because this record is not cleared for redistribution. coefficient of determination coefficient of determination Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. p-value p-value Quotation withheld because this record is not cleared for redistribution. standard deviation standard deviation Quotation withheld because this record is not cleared for redistribution. principal component analysis principal component analysis Quotation withheld because this record is not cleared for redistribution. multiple regression analysis multiple regression analysis Quotation withheld because this record is not cleared for redistribution. difference error in octaves difference error in octaves Quotation withheld because this record is not cleared for redistribution. SD of BF prediction errors SD of BF prediction errors Quotation withheld because this record is not cleared for redistribution. Vertical cells labelled from low-best-frequency AVCN injections lie in the anteroventral DCN and those labelled from high-best-frequency injections lie in the posterodorsal DCN, so vertical cells are tonotopically arranged. Quotation withheld because this record is not cleared for redistribution. A single spatial axis captures three quarters of the positional variance, so the frequency arrangement of vertical cells is essentially one-dimensional. Quotation withheld because this record is not cleared for redistribution. A linear equation predicting log best frequency from the three normalised spatial coordinates fitted the data closely. Quotation withheld because this record is not cleared for redistribution. Best frequencies predicted for each vertical cell from auditory-nerve innervation suggest vertical cell tonotopy is closely matched to the peripheral input map. Quotation withheld because this record is not cleared for redistribution. Only 11.8% of labelled vertical cells lay outside the reconstructed deep-layer boundary. Quotation withheld because this record is not cleared for redistribution. Injections at low best frequencies labelled more vertical cells than high-frequency injections, an unexplained asymmetry in cell numbers across the frequency axis. Quotation withheld because this record is not cleared for redistribution. The number of labelled vertical cells was not explained by injection size, because the extent of cochlear labelling correlated poorly with cell counts. Quotation withheld because this record is not cleared for redistribution. Pairs of vertical cells further apart in space tended to differ more in best frequency, though the relationship was moderate. Quotation withheld because this record is not cleared for redistribution. vertical cell position varies with frequency along an anteroventral to posterodorsal axis Quotation withheld because this record is not cleared for redistribution. the first principal component accounts for 75% of the variance, so the arrangement is essentially one-dimensional Quotation withheld because this record is not cleared for redistribution. BF is predicted from 3D position with R2 = 0.87 Quotation withheld because this record is not cleared for redistribution. an independent AN-derived frequency model predicts each cell's BF with R2 = 0.88 and near-zero mean error Quotation withheld because this record is not cleared for redistribution. several quantitative approaches converge on the same conclusion Quotation withheld because this record is not cleared for redistribution. 88.2% of labelled cells fall inside the independently reconstructed deep-layer surface Quotation withheld because this record is not cleared for redistribution. cell counts fall as BF rises, and the paper cannot explain it Quotation withheld because this record is not cleared for redistribution. cases with more labelled cells show no wider spread of BF prediction error Quotation withheld because this record is not cleared for redistribution. cells further apart in space differ more in BF, but only moderately Quotation withheld because this record is not cleared for redistribution. type II electrophysiological response type II electrophysiological response Quotation withheld because this record is not cleared for redistribution. spatial envelope spatial envelope Quotation withheld because this record is not cleared for redistribution. vertical cells vertical cells Quotation withheld because this record is not cleared for redistribution. type II electrophysiological response type II electrophysiological response Quotation withheld because this record is not cleared for redistribution. frequency region frequency region Quotation withheld because this record is not cleared for redistribution. body temperature body temperature Quotation withheld because this record is not cleared for redistribution. BF BF Quotation withheld because this record is not cleared for redistribution. Euclidian distance Euclidian distance Quotation withheld because this record is not cleared for redistribution. medial-lateral coordinate medial-lateral coordinate Quotation withheld because this record is not cleared for redistribution. dorsal-ventral coordinate dorsal-ventral coordinate Quotation withheld because this record is not cleared for redistribution. anterior-posterior coordinate anterior-posterior coordinate Quotation withheld because this record is not cleared for redistribution. 75% — share of the variance in normalised vertical cell position captured by the first principal component Quotation withheld because this record is not cleared for redistribution. R 2 = 0.87 — fit between best frequency and spatial position in the multiple regression model Quotation withheld because this record is not cleared for redistribution. R 2 = 0.88 — agreement between measured best frequencies and those predicted by the independent auditory-nerve frequency model Quotation withheld because this record is not cleared for redistribution. 11.8% — proportion of labelled vertical cells lying outside the reconstructed deep-layer boundary Quotation withheld because this record is not cleared for redistribution. 1259 — total number of labelled vertical cells normalised into the 3D DCN model Quotation withheld because this record is not cleared for redistribution. 48.4 ± 33.1 cells — mean number of vertical cells labelled per injection Quotation withheld because this record is not cleared for redistribution. 6.2 to 56 kHz — range of best frequencies of the AVCN recording/injection sites Quotation withheld because this record is not cleared for redistribution. 0.00 ± 0.30 oct. — mean error in octaves between regression-predicted and measured best frequency Quotation withheld because this record is not cleared for redistribution. Twenty-one — number of adult CBA/J mice used Quotation withheld because this record is not cleared for redistribution. 21 adult CBA/J mice, 2 male and 19 female — the sample Quotation withheld because this record is not cleared for redistribution. 26 recording sites, BFs 6.2 to 56 kHz, thresholds 8.6 to 37.6 dB SPL — the physiologically characterised injection sites Quotation withheld because this record is not cleared for redistribution. 11 to 128 labelled cells per injection, mean 48.4 plus or minus 33.1 — yield per case Quotation withheld because this record is not cleared for redistribution. 1259 cells — the merged dataset Quotation withheld because this record is not cleared for redistribution. 75% of variance on the first principal component — how one-dimensional the arrangement is Quotation withheld because this record is not cleared for redistribution. R2 = 0.87, P < 0.0001 — BF against 3D position by multiple regression Quotation withheld because this record is not cleared for redistribution. R2 = 0.88, errors -0.82 to 1.29 oct, mean 0.09 plus or minus 0.28 — accuracy of the independent frequency model's predictions Quotation withheld because this record is not cleared for redistribution. 11.8%, 148 of 1259, of which 98% lie within 40 microns of the surface — cells outside the independently drawn deep-layer boundary Quotation withheld because this record is not cleared for redistribution. R2 = 0.32, P < 0.003 — the unexplained relation between injection BF and cell count Quotation withheld because this record is not cleared for redistribution. R = 0.34, P = 0.092 — cochlear labelling spread against cell counts, offered as evidence that injection size did not drive the counts Quotation withheld because this record is not cleared for redistribution. R2 = 0.0002, P = 0.95 — SD of BF prediction error against cell count - the null that matters here Quotation withheld because this record is not cleared for redistribution. 748,356 pairs — cross-injection cell pairs compared for BF against distance Quotation withheld because this record is not cleared for redistribution.

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