Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex

Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex Gilad Gallero-Salas Groos Helmchen

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Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex 2018 Neuron 10.1016/j.neuron.2018.07.029 gilad2018-behavioral-strategy-determines-fro gilad2018-behavioral-strategy-determines-fro.txt, the project's staged copy 781003e968ac8f9ef1e7226683ec5bf42bea587a open-access neuroscience

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0 spans located by searching the stored text for the quote's exact words, allowing any whitespace between them mechanism Quotation withheld because this record is not cleared for redistribution. short-term memory localisation in mouse neocortex Quotation withheld because this record is not cleared for redistribution. calcium-imaging calcium-imaging Quotation withheld because this record is not cleared for redistribution. mechanisms Posterior parietal area RL, which projects both frontally to M2 and posteriorly to area P, routes the sensory information to one destination or the other according to the animal's behavioural state Quotation withheld because this record is not cleared for redistribution. mechanisms When information is held frontally in M2, posterior cortex is actively suppressed below baseline, which is why the two memory patterns are mutually exclusive Quotation withheld because this record is not cleared for redistribution. Wide-field signals are bulk population signals that may be confounded by non-neuronal fluorescence what this limits: every signal reported: Quotation withheld (AS WELL AS POTENTIALLY CONFOUNDED BY NON-NEURONAL FLUORESCENCE CHANGES, WHICH NEEDS TO BE CONTROLLED FOR) Quotation withheld because this record is not cleared for redistribution. Only layer 2/3 was studied; other layers may behave differently what this limits: the laminar reach of the conclusions: THIS STUDY FOCUSED ON LAYER 2/3 NEURONS, WHEREAS OTHER LAYERS MAY CONTRIBUTE DIFFERENTLY TO TASK-RELATED PROCESSES Quotation withheld because this record is not cleared for redistribution. The identity of the posterior activation spot is uncertain and may include neighbouring areas what this limits: the anatomical identity of the posterior activation: GIVEN THE VARIABILITY AMONG ANIMALS ... THE OBSERVED ACTIVATION SPOT MAY ALSO ENCOMPASS ADJACENT POSTERIOR AREAS SUCH AS LATEROMEDIAL VISUAL CORTEX OR POSTRHINAL CORTICES Quotation withheld because this record is not cleared for redistribution. The proposed what/where pathway interpretation is not directly tested here what this limits: the what/where pathway interpretation: ADDITIONAL EXPERIMENTS DIRECTLY TESTING EACH PATHWAY WILL BE NEEDED TO SUBSTANTIATE THESE IDEAS Quotation withheld because this record is not cleared for redistribution. The measurement is a bulk signal, and the authors state they cannot exclude having missed intermingled subpopulations averaged out within it. what this limits: the absence of task-relevant activity in an area of these maps: the signal is a bulk population measure and the authors state intermingled subpopulations could be averaged out within it Quotation withheld because this record is not cleared for redistribution. The grouping variable the entire result rests on is, in some sessions, assigned by a substitute measure whose accuracy is stated as 75%. what this limits: the active/passive trial labels in this study: in sessions without usable body-camera images they were predicted from a z-axis focus drop, reported at 75% accuracy against the camera Quotation withheld because this record is not cleared for redistribution. The independent variable is changed by the manipulation. Strategy is treated as what determines where short-term memory sits, but optogenetic silencing of the site induces strategy switches that persist across days and appear in non-perturbation trials. The paper reports this as a result rather than as a threat, and it is the correct reading - but it means strategy and site are mutually determining, not one prior to the other, and the title states only one direction. Quotation withheld because this record is not cleared for redistribution. Two thresholds on the same movement signal do different jobs: one splits trials into active and passive by movement during the sensation period, the other discards trials with movement in the first second of the delay as noisy. The grouping rule and the exclusion rule read the same measure, so which trials survive is not independent of which class they were assigned to. Quotation withheld because this record is not cleared for redistribution. a set of control experiments on the imaging signal itself eliminates: autofluorescence and non-calcium-related intrinsic signals as the source of the measured activity · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. control imaging targeted at the near-midline M2 area, which lies close to the superior sagittal sinus eliminates: hemodynamic signal as the source of the activity patterns, in the one location where a blood vessel makes it most likely · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. training two wild-type mice - carrying no GCaMP - on the same task and imaging them awake and performing eliminates: autofluorescence, by running the whole experiment in animals that cannot produce the signal of interest · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. cellular-resolution imaging run alongside the wide-field measurement eliminates: the possibility that the bulk population signal is not driven by the layer 2/3 cell bodies it is interpreted as reflecting · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. four experiments on the light delivery, including shining light on cortex not expressing ArchT in the same mice - one record for the set, quoting the sentence that reports the outcome eliminates: light disturbance itself as the cause of the behavioural effect, and establishes that the effect requires the right population at the right time · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. short-term memory short-term memory Quotation withheld because this record is not cleared for redistribution. behavioral strategy behavioral strategy Quotation withheld because this record is not cleared for redistribution. wide-field wide-field Quotation withheld because this record is not cleared for redistribution. activeness activeness Quotation withheld because this record is not cleared for redistribution. quiet trials quiet trials Quotation withheld because this record is not cleared for redistribution. M2 M2 Quotation withheld because this record is not cleared for redistribution. z-axis drop in focus z-axis drop in focus Quotation withheld because this record is not cleared for redistribution. location of short-term memory - NOT A SINGLE SITE: medio-frontal on active trials and lateral posterior on passive ones, so the answer is conditional on the animal's strategy Quotation withheld because this record is not cleared for redistribution. behavioral strategy - an experimental grouping made from the animal's own conduct: engaging the body toward the approaching texture, or passively awaiting the touch Quotation withheld because this record is not cleared for redistribution. active versus passive trial - operationalised by thresholding body movement during the sensation period, so the class is fixed by a cut on a continuous measure Quotation withheld because this record is not cleared for redistribution. delay period - AS ANALYSED, NOT AS RUN: restricted to `quiet trials` in which the mouse did not move for at least the first second, with traces truncated at the first movement thereafter. THIS IS A CONTROL, NOT A CONFOUND - the classes are defined by movement during the SENSATION period, and the delay analysis is made movement-free on purpose so that the persistent activity cannot be motor activity Quotation withheld because this record is not cleared for redistribution. replicates → Chen et al., 2016; Yang et al., 2015 (choice encoding in posterior sensory areas) Quotation withheld because this record is not cleared for redistribution. replicates → Chen et al., 2013, 2016 (timing of hit/CR discrimination) Quotation withheld because this record is not cleared for redistribution. extends → Guo et al., 2014; Li et al., 2015 (frontal areas including ALM as the site of short-term memory) Quotation withheld because this record is not cleared for redistribution. builds-on → Leavitt et al., 2017 (sustained activity encoding working memory is not fully distributed) Quotation withheld because this record is not cleared for redistribution. Wilcoxon signed-rank test and Mann-Whitney U-test Wilcoxon signed-rank test and 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. F statistic with 95% confidence interval F statistic with 95% confidence interval Quotation withheld because this record is not cleared for redistribution. Kolmogorov-Smirnov test Kolmogorov-Smirnov test Quotation withheld because this record is not cleared for redistribution. support vector machine with cross-validation support vector machine with cross-validation Quotation withheld because this record is not cleared for redistribution. label-shuffling permutation test label-shuffling permutation test 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. ROC analysis / area under the curve ROC analysis / area under the curve Quotation withheld because this record is not cleared for redistribution. correlation coefficient correlation coefficient Quotation withheld because this record is not cleared for redistribution. Bonferroni correction Bonferroni correction Quotation withheld because this record is not cleared for redistribution. Which cortical area held the delay-period memory depended on the mouse's behavioural strategy: persistent activity sat medio-frontally (M2) on active trials but in a lateral posterior area on passive trials. Quotation withheld because this record is not cleared for redistribution. The posterior whisker areas encoded the animal's choice soon after touch under both strategies, so the strategy difference appeared only later, during the delay. Quotation withheld because this record is not cleared for redistribution. Optogenetically silencing M2 or area P lowered task performance only in trials run with the strategy that area supports, and left the other strategy unaffected. Quotation withheld because this record is not cleared for redistribution. Silencing M2 and area P together significantly reduced performance in all four VGAT-ChR2 mice, to levels not significantly different from the expert threshold. Quotation withheld because this record is not cleared for redistribution. One passive mouse switched its strategy from passive to active in the perturbation sessions. Quotation withheld because this record is not cleared for redistribution. The two memory sites hold different content: the motor-sensory index was positive in M2 (activity grouped by the upcoming action) and negative in area P (activity grouped by the past texture). Quotation withheld because this record is not cleared for redistribution. On passive trials a classifier restricted to frontal-cortex pixels was at chance distinguishing hit from correct-rejection trials. Quotation withheld because this record is not cleared for redistribution. Discrimination performance (d') correlated positively with how actively a mouse used its whiskers (r = 0.6). Quotation withheld because this record is not cleared for redistribution. activeness activeness Quotation withheld because this record is not cleared for redistribution. active versus passive trial active versus passive trial Quotation withheld because this record is not cleared for redistribution. motor-sensory index (MSI) motor-sensory index (MSI) Quotation withheld because this record is not cleared for redistribution. posterior area P posterior area P Quotation withheld because this record is not cleared for redistribution. layer 2/3 neuronal activity layer 2/3 neuronal activity Quotation withheld because this record is not cleared for redistribution. d-prime d-prime Quotation withheld because this record is not cleared for redistribution. body movement body movement Quotation withheld because this record is not cleared for redistribution. 16 and 82% — range of activeness (percentage of hit trials with body movement at texture touch) across the eight imaged mice Quotation withheld because this record is not cleared for redistribution. 60-88% — accuracy of the classifier separating hit from correct-rejection delay maps, across mice and both strategies Quotation withheld because this record is not cleared for redistribution. 48.5 ± 4.2 and 50.4 ± 3.8 — classifier accuracy after shuffling trial labels, i.e. the chance baseline for active and passive trials Quotation withheld because this record is not cleared for redistribution. r = 0.6 — correlation between a session's activeness and the mouse's d-prime discrimination performance Quotation withheld because this record is not cleared for redistribution. 6.9 ± 0.3 weeks — training time needed before imaging, across the eight mice Quotation withheld because this record is not cleared for redistribution. 1.2-4.5 s — range of enforced delay durations mice could withhold licking for Quotation withheld because this record is not cleared for redistribution. 2.89° ± 0.36° vs. 0.95° ± 0.14° — whisking envelope around texture arrival on active versus passive trials Quotation withheld because this record is not cleared for redistribution. 30 — total adult male mice used across imaging, control and optogenetic experiments 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.neuron.2018.07.029.