Development of Inhibitory Timescales in Auditory Cortex

Development of Inhibitory Timescales in Auditory Cortex Oswald Reyes

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Development of Inhibitory Timescales in Auditory Cortex 2011 Cerebral Cortex 10.1093/cercor/bhq214 Oswald2011-development-of-inhibitory-timescales-in-audi Oswald2011-development-of-inhibitory-timescales-in-audi.txt, the project's staged copy 692709e71320df0ec1ca147fe4d0edeae7b7221c 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 how the timing of cortical inhibition matures over the weeks after hearing onset Quotation withheld because this record is not cleared for redistribution. which intrinsic and synaptic properties set the speed of inhibitory recruitment, and how each changes between P10 and P29 Quotation withheld because this record is not cleared for redistribution. shows fast-spiking cells and their synapses both speed up over development, and that the temporal properties of inhibition mature later than those of excitation Quotation withheld because this record is not cleared for redistribution. mechanism Quotation withheld because this record is not cleared for redistribution. postnatal development of inhibitory timing in auditory cortex layer 2/3 Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms Shortening of the postsynaptic membrane time constant during development speeds the decay of synaptic potentials Quotation withheld because this record is not cleared for redistribution. mechanisms Falling input resistance of the postsynaptic pyramidal cell offsets a rising inhibitory current, so the measured IPSP amplitude declines with age Quotation withheld because this record is not cleared for redistribution. mechanisms Later IPSP peak times in young animals reduce excitation-inhibition overlap and thereby widen the synaptic integration window Quotation withheld because this record is not cleared for redistribution. mechanisms Inhibitory decay constants longer than excitatory ones impose an upper frequency limit on responses to closely spaced inputs Quotation withheld because this record is not cleared for redistribution. mechanisms Developmental expression of leak and repolarizing potassium channels in PV+ FS cells drives the change in intrinsic excitability Quotation withheld because this record is not cleared for redistribution. mechanisms A switch from slow alpha-3 to faster alpha-1 GABA_A receptor subunits accelerates IPSP rise and decay Quotation withheld because this record is not cleared for redistribution. faster firing in older cells follows from shorter membrane time constants, briefer afterhyperpolarisations and narrower spikes Quotation withheld because this record is not cleared for redistribution. the speed-up coincides with development of potassium channels handling leak and spike repolarisation Quotation withheld because this record is not cleared for redistribution. excitatory decay tracks the membrane time constant of the receiving cell, so a synaptic timescale is partly a membrane timescale Quotation withheld because this record is not cleared for redistribution. inhibitory rise, peak and decay times shorten with age, attributed in part to the falling membrane time constant of the receiving pyramidal cell Quotation withheld because this record is not cleared for redistribution. shorter inhibitory decays let older cells follow inputs at 20-40 Hz where younger ones summate and stop responding above 10 Hz Quotation withheld because this record is not cleared for redistribution. Voltage clamp was deliberately not used, limiting the measurements to current-clamp postsynaptic potentials. what this limits: every synaptic measurement in the paper: VOLTAGE CLAMP RECORDINGS WERE NOT PERFORMED BECAUSE THE STANDARD INTERNAL SOLUTIONS ... WOULD PROHIBIT THE CHARACTERIZATION OF INTRINSIC NEURAL P[roperties] - one measurement excludes the other Quotation withheld because this record is not cleared for redistribution. Whether the paired-cell changes in inhibitory strength hold at the population level in vivo is unknown. what this limits: the extrapolation from paired recordings to the intact animal: IT REMAINS TO BE DETERMINED HOW CHANGES IN INHIBITORY STRENGTH BETWEEN PAIRS OF NEURONS ARE REFLECTED AT THE POPULATION LEVEL IN VIVO Quotation withheld because this record is not cleared for redistribution. The functional consequences for auditory processing were not tested and require in vivo work. what this limits: any functional claim about auditory processing: FURTHER IN VIVO STUDIES ARE NECESSARY TO ELUCIDATE FUNCTIONAL IMPLICATIONS Quotation withheld because this record is not cleared for redistribution. Identifying fast-spiking cells electrophysiologically is unreliable in the youngest animals. what this limits: the fast-spiking classification in the youngest animals: THE IDENTIFICATION OF FS CELLS BASED ON ELECTROPHYSIOLOGICAL PROPERTIES CAN BE DIFFICULT PARTICULARLY IN YOUNG ANIMALS (P10-P14) SINCE FS RESPONSES ARE LESS APPARENT Quotation withheld because this record is not cleared for redistribution. voltage clamp was deliberately not used, because the solutions needed for it would have prevented measuring intrinsic properties and bidirectional connections duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - the trade-off between clamp quality and intrinsic properties Quotation withheld because this record is not cleared for redistribution. the age bins were divided arbitrarily what this limits: every developmental comparison in the paper: THE TRANSITIONAL PERIOD WAS DIVIDED ARBITRARILY INTO AN EARLY PHASE (P10-P14) - the independent variable's boundaries are declared arbitrary Quotation withheld because this record is not cleared for redistribution. only postsynaptic potentials that fitted the double-exponential model well were analysed what this limits: the fitted decay parameters: ONLY PSPS THAT WERE WELL FIT BY EQUATION 1 (CHI2 < 1.75) WERE CHOSEN - a goodness-of-fit threshold decides which data enter Quotation withheld because this record is not cleared for redistribution. receptor composition changes are not excluded as an additional cause of the synaptic decay changes what this limits: the mechanistic attribution of the decay changes: OUR RESULTS DO NOT PRECLUDE THE POSSIBILITY THAT DEVELOPMENTAL CHANGES IN AMPA AND/OR NMDA RECEPTOR COMPOSITION also contribute Quotation withheld because this record is not cleared for redistribution. how paired-cell inhibitory strength maps onto the population level in the intact animal is left open duplicate of: limitations[1] · what this limits: the same scope as limitations[1] - paired cells versus population in vivo Quotation withheld because this record is not cleared for redistribution. a GFP line used not as the object of study but as a check on an electrophysiological classification Quotation withheld because this record is not cleared for redistribution. the expectation that a synaptic potential's time course follows the membrane time constant of the cell receiving it Quotation withheld because this record is not cleared for redistribution. the location of AI verified in a subset of slices by stimulating the MG and recording field potential responses in layers 3 and 4 eliminates: recording from the wrong cortical field - the functional check is independent of the stereotaxic estimate it verifies · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. EPSPs → FS cell membrane time constants CORRELATED THROUGHOUT DEVELOPMENT, with no manipulation of either quantity. Recording it as 'causes' in either direction asserts more than the sentence does. Quotation withheld because this record is not cleared for redistribution. FS is an ELECTROPHYSIOLOGICAL category whose defining features are absent in the youngest animals, which is exactly the age this paper is about Quotation withheld because this record is not cleared for redistribution. the transgenic label covers only a SUBSET - the PV cells that are also fast-spiking express EGFP - so GFP-positive is narrower than PV-positive Quotation withheld because this record is not cleared for redistribution. IPSP and IPSC are not interchangeable measures of inhibitory strength: they differ by the postsynaptic input resistance, which itself falls with age Quotation withheld because this record is not cleared for redistribution. reported PSP amplitudes are averaged over all trials INCLUDING failures, so they are a product of size and reliability rather than a size alone Quotation withheld because this record is not cleared for redistribution. a successful PSP is defined by a three-part criterion on onset, amplitude and peak time, with anything else counted as a failure of amplitude zero Quotation withheld because this record is not cleared for redistribution. claim_type: mechanism a second reading reaching the same value. Recorded: mechanism — 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: paired whole-cell current-clamp recording from connected fast-spiking and pyramidal cells in auditory thalamocortical slices across three age bins 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: the developmental narrowing of the synaptic integration window in auditory cortex a second reading DIFFERING from the recorded value. Recorded: postnatal development of inhibitory timing in auditory cortex layer 2/3 — 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 → Oswald and Reyes 2008 (development of L2/3 pyramidal cells in AI) Quotation withheld because this record is not cleared for redistribution. builds-on → Oswald and Reyes 2008 (companion study on PC–PC circuitry) Quotation withheld because this record is not cleared for redistribution. contradicts → Doischer et al. 2008; Kobayashi et al. 2008 (age-related increase in IPSC amplitude in other cortical areas) Quotation withheld because this record is not cleared for redistribution. contradicts → Dorrn et al. 2010; Sun et al. 2010 (in vivo reports that inhibitory strength is stable in early development) Quotation withheld because this record is not cleared for redistribution. contradicts → reports from other cortical areas that inhibitory postsynaptic amplitudes increase with age Quotation withheld because this record is not cleared for redistribution. reconciles → that disagreement, by proposing that falling input resistance converts a rising current into a falling voltage Quotation withheld because this record is not cleared for redistribution. extends → their own companion study on pyramidal cell development in the same layer Quotation withheld because this record is not cleared for redistribution. supports → the proposal that inhibitory tuning lags excitatory tuning, which the paper notes is itself disputed Quotation withheld because this record is not cleared for redistribution. builds-on → in vivo work on thalamorecipient layers, by adding the supragranular circuit Quotation withheld because this record is not cleared for redistribution. input resistance —causes→ IPSP input resistance IPSP strength of the relation: 1 · note: the conversion factor between the measures is itself a developing variable, which is why a cross-paper comparison of inhibitory strength needs to know which was measured Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but 'one LIKELY explanation' is that decreasing input resistance counters rising IPSC amplitude; causes is hedged. Quotation withheld because this record is not cleared for redistribution. membrane time constant —causes→ IPSP membrane time constant IPSP strength of the relation: 0.8 · note: same route on the inhibitory side, with a receptor subunit switch offered as an additional cause Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the IPSP time changes 'MAY, in part, be attributed to' the membrane time constant; causes is hedged. Quotation withheld because this record is not cleared for redistribution. GABA A —causes→ IPSP GABA A IPSP strength of the relation: 0.7 · note: the alpha-3 to alpha-1 switch; an alternative not separated from the membrane route here Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the GABA A subunit transition 'MAY ALSO contribute' to IPSP kinetics; causes is hedged. Quotation withheld because this record is not cleared for redistribution. FS —contrasted-with→ PCs FS PCs strength of the relation: 1 · note: the mature separation rests on firing rate, spike width and afterhyperpolarisation - all of which are absent before P15 Quotation withheld because this record is not cleared for redistribution. IPSP —causes→ integration window IPSP integration window strength of the relation: 1 · note: SIGN: later inhibitory peaks widen the window, so young cells accept less precisely timed inputs Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but later-peaking IPSPs 'WOULD LIKELY' broaden the integration window; causes is hedged. Quotation withheld because this record is not cleared for redistribution. short-term depression —operationalised-as→ paired pulse ratio short-term depression paired pulse ratio strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. ANOVA ANOVA Quotation withheld because this record is not cleared for redistribution. Tukey's HSD post hoc test Tukey's HSD post hoc test Quotation withheld because this record is not cleared for redistribution. Levene's test for homogeneity of variance Levene's test for homogeneity of variance Quotation withheld because this record is not cleared for redistribution. Mann-Whitney U test Mann-Whitney U test Quotation withheld because this record is not cleared for redistribution. standard deviation standard deviation Quotation withheld because this record is not cleared for redistribution. least-squares curve fitting (chi-squared minimisation) least-squares curve fitting (chi-squared minimisation) Quotation withheld because this record is not cleared for redistribution. correlation correlation Quotation withheld because this record is not cleared for redistribution. F statistic F statistic about this quote: This quote ends with the stray word 'The', the first word of the next sentence. It is not trimmed, because the quote without it occurs more than once in the paper's text and could not be tied to one place. The claim is carried by the sentence before 'The'. Quotation withheld because this record is not cleared for redistribution. Mann–Whitney U test Mann–Whitney U test Quotation withheld because this record is not cleared for redistribution. ANOVA ANOVA Quotation withheld because this record is not cleared for redistribution. Between P10 and P29 the firing rates of fast-spiking interneurons rose, driven by shorter membrane time constants, briefer afterhyperpolarizations and narrower action potentials. Quotation withheld because this record is not cleared for redistribution. IPSP latency, rise time and peak time, together with the decay constants of both EPSPs and IPSPs, all shortened between P10 and P29. Quotation withheld because this record is not cleared for redistribution. Excitatory PC-to-FS synapses in the youngest animals depressed most strongly (paired-pulse ratio 0.4) and this depression weakened with age (0.7 at P15-P18 and 0.8 at P19-P29). Quotation withheld because this record is not cleared for redistribution. Because short-term depression at PC-to-FS synapses weakened with age, older synapses sustained their responses better during repetitive stimulation. Quotation withheld because this record is not cleared for redistribution. The temporal properties that determine when inhibition is recruited mature later than the corresponding properties of excitation. Quotation withheld because this record is not cleared for redistribution. IPSP amplitude fell from 0.8 mV at P10-P14 to 0.5 mV at P19-P29. Quotation withheld because this record is not cleared for redistribution. The EPSP decay time constant shortened from 37 ms at P10-P14 to 16 ms at P19-P29 while the rise time constant did not change with age. Quotation withheld because this record is not cleared for redistribution. FS-to-PC inhibitory responses to single pulses were entirely GABA_A-receptor mediated, being abolished by bicuculline. Quotation withheld because this record is not cleared for redistribution. At resting potential, PC-to-FS excitatory responses were entirely AMPA-receptor mediated, being abolished by DNQX. Quotation withheld because this record is not cleared for redistribution. FS-cell intrinsic membrane and action-potential properties were indistinguishable between the GFP-expressing G42 line and Swiss Webster mice at every age tested. Quotation withheld because this record is not cleared for redistribution. Except for latency, the rise, peak and decay of the IPSP were significantly longer than the corresponding excitatory timescales. Quotation withheld because this record is not cleared for redistribution. Fast-spiking cells at P10-P14 were the least mature electrically, with the longest membrane time constants, highest input resistance and most depolarized resting potential. Quotation withheld because this record is not cleared for redistribution. spikes narrowed and afterhyperpolarisations shortened with age, raising firing rates Quotation withheld because this record is not cleared for redistribution. the hyperpolarisation-activated sag was prominent at P10-P14 Quotation withheld because this record is not cleared for redistribution. excitatory amplitudes fell with age and correlated with input resistance across all ages Quotation withheld because this record is not cleared for redistribution. short-term depression at excitatory synapses weakened with age, making repetitive responses more sustained Quotation withheld because this record is not cleared for redistribution. inhibitory rise, peak and decay times all shortened with age Quotation withheld because this record is not cleared for redistribution. inhibitory decays stayed longer than excitatory ones at every age, setting an upper frequency bound Quotation withheld because this record is not cleared for redistribution. properties transitioned between P10 and P18 and plateaued from P19 to P29 Quotation withheld because this record is not cleared for redistribution. excitatory potentials were fully blocked by an AMPA receptor antagonist Quotation withheld because this record is not cleared for redistribution. CONTROL: GFP-labelled cells in the transgenic line and electrophysiologically identified cells did not differ at any age Quotation withheld because this record is not cleared for redistribution. UNEXPECTED RESULT: inhibitory potential amplitudes fell with age, where other cortical areas report the current rising Quotation withheld because this record is not cleared for redistribution. RESOLUTION OFFERED: falling input resistance would convert a rising inhibitory current into a falling inhibitory voltage Quotation withheld because this record is not cleared for redistribution. the classification of fast-spiking cells is hardest exactly in the youngest animals, where the defining responses are less apparent Quotation withheld because this record is not cleared for redistribution. spike frequency adaptation spike frequency adaptation Quotation withheld because this record is not cleared for redistribution. failure rate failure rate Quotation withheld because this record is not cleared for redistribution. paired pulse ratio paired pulse ratio Quotation withheld because this record is not cleared for redistribution. EPSP latency EPSP latency Quotation withheld because this record is not cleared for redistribution. PSP latency PSP latency Quotation withheld because this record is not cleared for redistribution. spike threshold spike threshold Quotation withheld because this record is not cleared for redistribution. amplitude of the sag amplitude of the sag Quotation withheld because this record is not cleared for redistribution. paired pulse ratio paired pulse ratio Quotation withheld because this record is not cleared for redistribution. integration window integration window Quotation withheld because this record is not cleared for redistribution. sag sag Quotation withheld because this record is not cleared for redistribution. step current step current Quotation withheld because this record is not cleared for redistribution. IPSP amplitude IPSP amplitude Quotation withheld because this record is not cleared for redistribution. decay of the EPSP decay of the EPSP Quotation withheld because this record is not cleared for redistribution. reversal potential reversal potential Quotation withheld because this record is not cleared for redistribution. membrane time constant membrane time constant Quotation withheld because this record is not cleared for redistribution. paired pulse ratio paired pulse ratio Quotation withheld because this record is not cleared for redistribution. input resistance input resistance Quotation withheld because this record is not cleared for redistribution. 116 FS cells / 134 PCs — number of fast-spiking interneurons recorded and pyramidal cells they were synaptically connected to Quotation withheld because this record is not cleared for redistribution. 0.4 ± 0.1 vs 0.8 ± 0.2 — paired-pulse ratio at PC-to-FS synapses in the youngest versus oldest age group Quotation withheld because this record is not cleared for redistribution. 1.4 ± 0.3 — spike-frequency adaptation ratio (last/first interspike interval) in P10-P14 FS cells, higher than in older animals Quotation withheld because this record is not cleared for redistribution. 23 ± 11 ms; 294 ± 183 MΩ — membrane time constant and input resistance of FS cells at P10-P14, the highest values recorded Quotation withheld because this record is not cleared for redistribution. R : 0.88 — correlation between mean EPSP decay constant and mean FS-cell membrane time constant across ages Quotation withheld because this record is not cleared for redistribution. R : 0.77 — correlation between postsynaptic pyramidal-cell input resistance and mean IPSP amplitude Quotation withheld because this record is not cleared for redistribution. χ 2 < 1.75, n = 155 EPSPs, n = 167 IPSPs — goodness-of-fit cutoff and the number of postsynaptic potentials that passed it for kinetic analysis Quotation withheld because this record is not cleared for redistribution. 60–200 ms — IPSP duration in young animals, long enough to summate and suppress responsiveness above 10 Hz Quotation withheld because this record is not cleared for redistribution. 25–50 ms — IPSP duration in older animals, permitting responses to 20-40 Hz inputs Quotation withheld because this record is not cleared for redistribution. 116 and 134 — fast-spiking cells and connected pyramidal cells recorded Quotation withheld because this record is not cleared for redistribution. P10 to P29 — age range, spanning hearing onset to the plateau Quotation withheld because this record is not cleared for redistribution. 60-200 ms against 25-50 ms — inhibitory potential durations in young against older animals Quotation withheld because this record is not cleared for redistribution. above 10 Hz against 20-40 Hz — input frequencies the young and older circuits can follow Quotation withheld because this record is not cleared for redistribution. 0.4 against 0.8 — paired pulse ratio at 10 Hz in the youngest against the oldest group Quotation withheld because this record is not cleared for redistribution. 72 — neurons filled with biocytin to confirm identity morphologically Quotation withheld because this record is not cleared for redistribution.

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