Dynamics of social representation in the mouse prefrontal cortex

Dynamics of social representation in the mouse prefrontal cortex Levy Tamir Kaufman Parabucki Weissbrod Schneidman Yizhar

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Dynamics of social representation in the mouse prefrontal cortex 2019 Nature Neuroscience 10.1038/s41593-019-0531-z levy2019-dynamics-of-social-representation levy2019-dynamics-of-social-representation.txt, the project's staged copy 57c3a35c76a00f7934ce792febe763e44b8d9cba 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 existence Quotation withheld because this record is not cleared for redistribution. social representation in medial prefrontal cortex Quotation withheld because this record is not cleared for redistribution. electrophysiology electrophysiology Quotation withheld because this record is not cleared for redistribution. mechanisms Elevated baseline cortical noise degrades the mPFC's ability to form category-specific social representations and to drive the synaptic plasticity that refines them Quotation withheld because this record is not cleared for redistribution. mechanisms Loss of CNTNAP2 impairs targeting of AMPA and NMDA receptors to post-synaptic membranes, removing the plasticity that would otherwise refine odour-category representations with experience Quotation withheld because this record is not cleared for redistribution. The social/nonsocial distinction is a distinction between two sets of odours. what this limits: any claim that this mPFC activity encodes social information: the tuning measure is the normalised odor-evoked response magnitude, and it was higher for male and female cues than for all nonsocial odors Quotation withheld because this record is not cleared for redistribution. Two of the three behavioural measures did not differ between social and nonsocial stimuli. what this limits: any behavioural evidence that the mice treated social cues differently: orientation probability was higher for social cues, while response latency and the stimulus-evoked increase in locomotion did not significantly differ Quotation withheld because this record is not cleared for redistribution. The paper's central quantity is a log ratio of distances between activity patterns. what this limits: any social distinction index quoted from this work: it was calculated to quantify the separation between the representations of social and nonsocial stimuli for each mouse Quotation withheld because this record is not cleared for redistribution. baseline firing rate and locomotion as explanations for the elevated noise eliminates: the reading that the knockouts' higher baseline noise is a rate or movement artefact · outcome (stated by the tagger, no quotation): held Quotation withheld because this record is not cleared for redistribution. social distinction index social distinction index Quotation withheld because this record is not cleared for redistribution. nonsocial odors nonsocial odors Quotation withheld because this record is not cleared for redistribution. odor-evoked response magnitude odor-evoked response magnitude Quotation withheld because this record is not cleared for redistribution. separation separation Quotation withheld because this record is not cleared for redistribution. baseline noise levels baseline noise levels Quotation withheld because this record is not cleared for redistribution. a social stimulus, here - AN ODOUR FROM A CONSPECIFIC: the tuning measure is odor-evoked response magnitude, higher for male and female cues than for all nonsocial odors regardless of odor identity, so every 'social' difference reported is a difference between two sets of smells Quotation withheld because this record is not cleared for redistribution. the social distinction index - A LOG RATIO OF POPULATION DISTANCES: introduced to quantify the separation between social and nonsocial representations per mouse, so a phrase that reads as a faculty names a ratio between distances among activity patterns - and the paper prints the formula beside the name Quotation withheld because this record is not cleared for redistribution. the behavioural evidence - ONE DIFFERENCE OUT OF THREE MEASURES: orientation probability was higher for social cues while response latency and locomotion increase did not significantly differ, so the animals' overt behaviour separates the categories on one axis and not on two Quotation withheld because this record is not cleared for redistribution. extends → prior work on experience-dependent divergence of conspecific sex representations in hypothalamus and medial amygdala Quotation withheld because this record is not cleared for redistribution. builds-on → Lazaro et al., "Reduced prefrontal synaptic connectivity and disturbed oscillatory population dynamics in the CNTNAP2 model of autism" (bioRxiv 2018) Quotation withheld because this record is not cleared for redistribution. separation —operationalised-as→ social distinction index separation social distinction index strength of the relation: 1 Quotation withheld because this record is not cleared for redistribution. Friedman test Friedman 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. t-test t-test Quotation withheld because this record is not cleared for redistribution. chi-squared chi-squared Quotation withheld because this record is not cleared for redistribution. standardized residuals standardized residuals Quotation withheld because this record is not cleared for redistribution. z-score z-score Quotation withheld because this record is not cleared for redistribution. Bonferroni correction Bonferroni correction Quotation withheld because this record is not cleared for redistribution. Levene's test Levene's 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. cross-validation cross-validation Quotation withheld because this record is not cleared for redistribution. multiple regression multiple regression Quotation withheld because this record is not cleared for redistribution. maximum likelihood classification maximum likelihood classification 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. In the mouse medial prefrontal cortex, nearly a quarter of recorded units were selective for social odours, twice as many as were selective for nonsocial odours or showed mixed responses. Quotation withheld because this record is not cleared for redistribution. The mPFC population code is organised by social versus nonsocial category rather than by odour identity or valence: responses to the two social cues were more similar to each other than to any nonsocial odour. Quotation withheld because this record is not cleared for redistribution. Average unit tuning was stronger for both male and female social cues than for any of the three nonsocial odours, independent of odour identity. Quotation withheld because this record is not cleared for redistribution. In wild-type mice the social distinction index rose significantly from the first to the second recording day, showing experience-dependent refinement of the social representation. Quotation withheld because this record is not cleared for redistribution. Cntnap2 knockout mice showed no experience-dependent change: their social distinction index was unchanged between the two recording sessions. Quotation withheld because this record is not cleared for redistribution. The autism-model deficit is specific to categorisation rather than to stimulus encoding: single-odour decoding was equally accurate in both genotypes, but social/nonsocial category decoding was significantly worse in Cntnap2 knockouts. Quotation withheld because this record is not cleared for redistribution. Baseline (ongoing) population activity was noisier in Cntnap2 knockout mice than in wild-type littermates, with the two genotypes almost completely non-overlapping on this measure. Quotation withheld because this record is not cleared for redistribution. Mean baseline firing rates of mPFC units were higher in Cntnap2 knockout mice than in wild-type littermates. Quotation withheld because this record is not cleared for redistribution. Across both genotypes, the level of baseline neuronal noise was strongly negatively correlated with the social distinction index. Quotation withheld because this record is not cleared for redistribution. Baseline cortical noise predicted how much a mouse's social representation refined with experience: higher noise went with a smaller day-to-day gain in the social distinction index. Quotation withheld because this record is not cleared for redistribution. The neural preference for social cues was not explained by behaviour: latency to orient and stimulus-evoked locomotion did not differ between social and nonsocial odours. Quotation withheld because this record is not cleared for redistribution. social distinction index social distinction index Quotation withheld because this record is not cleared for redistribution. Jensen-Shannon divergence Jensen-Shannon divergence Quotation withheld because this record is not cleared for redistribution. cortical noise cortical noise Quotation withheld because this record is not cleared for redistribution. unit tuning unit tuning Quotation withheld because this record is not cleared for redistribution. evoked firing rate evoked firing rate Quotation withheld because this record is not cleared for redistribution. cortical noise level cortical noise level Quotation withheld because this record is not cleared for redistribution. locomotion level locomotion level Quotation withheld because this record is not cleared for redistribution. n = 194 — number of mPFC single units recorded in the first cohort of six mice Quotation withheld because this record is not cleared for redistribution. 44% — proportion of recorded mPFC units that responded to at least one odour stimulus Quotation withheld because this record is not cleared for redistribution. 51% — proportion of responsive units that responded to only one specific stimulus Quotation withheld because this record is not cleared for redistribution. from 44% on day 1 to 58% on day 2 — rise in the share of non-responsive units in Cntnap2 knockout mice across the two sessions Quotation withheld because this record is not cleared for redistribution. 269 / 237 — total units recorded in Cntnap2 knockout mice versus wild-type littermates across both days Quotation withheld because this record is not cleared for redistribution. 75% — variance in population activity captured by the first two principal components in the example projection Quotation withheld because this record is not cleared for redistribution. social = 98.33 ± 1.05, nonsocial = 87.22 ± 3.03, clean air = 65 ± 7.63 — mean probability of an odour-evoked orientation response by stimulus class Quotation withheld because this record is not cleared for redistribution. t(103) = 3.285, P < 0.01 — test of the higher evoked response magnitude to social versus nonsocial stimuli Quotation withheld because this record is not cleared for redistribution.

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