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W4313012224 abstract "Article Figures and data Abstract Editor's evaluation Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53/Baiap2-mutant mice, which show social deficits, during social approach. We found a decrease in the proportion of IRSp53-mutant excitatory mPFC neurons encoding social information, but not that encoding non-social information. In addition, the firing activity of IRSp53-mutant neurons was less differential between social and non-social targets. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing, but decreases in the variability and dynamic range of firing as well as burst firing during social and non-social target approaches compared to wild-type controls. Treatment of memantine, an NMDA receptor antagonist that rescues social deficit in IRSp53-mutant mice, alleviates the reduced burst firing of IRSp53-mutant pyramidal mPFC neurons. These results suggest that suppressed neuronal activity dynamics and burst firing may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice. Editor's evaluation This study by Kim et al. is of interest to neuroscientists studying neocortical neural activity, as related to social behavior and in mouse models of neuropsychiatric disorders. These results provide new data on how the loss of the postsynaptic scaffolding and adaptor protein IRSp53 impacts prefrontal cortex activity and social interaction in mice. The authors propose the interesting idea that suppressed neuronal activity dynamics and burst firing may contribute to the impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice. https://doi.org/10.7554/eLife.74998.sa0 Decision letter Reviews on Sciety eLife's review process Introduction Social dysfunction is a key feature of various neuropsychiatric disorders, including autism spectrum disorders (ASD), schizophrenia, and attention-deficit/hyperactivity disorders (ADHD). Among the various brain regions involved in social regulation, the medial prefrontal cortex (mPFC) plays critical roles in integrative and higher cognitive brain functions (Yan and Rein, 2022; Yizhar and Levy, 2021). Previous studies identified a number of mechanisms associated with dysfunctions under a social context. Examples include an imbalance of neuronal excitation/inhibition (Selimbeyoglu et al., 2017; Yizhar et al., 2011) (reviewed in Lee et al., 2017; Nelson and Valakh, 2015; Sohal and Rubenstein, 2019), impaired cortical social representation (Lee et al., 2021a; Lee et al., 2021b; Lee et al., 2016; Levy et al., 2019; Miura et al., 2020), and the disruption of local oscillations (Cao et al., 2018; Yizhar et al., 2011). Given that social behaviors represent outcomes of complex interactions among multiple underlying neural processes, further mechanistic explorations are needed to be investigated in the context of additional genes and various psychiatric disorders. Insulin receptor substrate protein 53 kDa (IRSp53) encoded by the BAIAP2 gene is a postsynaptic scaffolding and adaptor protein at excitatory synapses that interacts with other key components of the postsynaptic density such as PSD-95 (Choi et al., 2005; Soltau et al., 2004). IRSp53 has also been implicated in ASD (Celestino-Soper et al., 2011; Levy et al., 2011; Toma et al., 2011; Wu et al., 2020), schizophrenia (Fromer et al., 2014; Genovese et al., 2016; Johnson et al., 2016; Purcell et al., 2014) and ADHD (Bonvicini et al., 2016; Liu et al., 2013; Ribasés et al., 2009). Functionally, IRSp53 regulates actin filament dynamics at excitatory synapses and dendritic spines (Kang et al., 2016; Scita et al., 2008). IRSp53 deficiency in mice leads to excitatory synaptic deficits and various behavioral deficits, including hyperactivity, cognitive impairments, and social deficits (Bobsin and Kreienkamp, 2016; Chung et al., 2015; Kim et al., 2009; Kim et al., 2020b; Sawallisch et al., 2009). IRSp53 knockout (KO) mice have fewer dendritic spines and enhanced NMDA receptor (NMDAR) function; they show impaired social behavior that is rescued by pharmacological NMDAR suppression (Chung et al., 2015; Kim et al., 2009). Importantly, mPFC neurons in IRSp53-KO mice show reduced neuronal firing under urethane-anesthesia, which is acutely normalized by pharmacological NMDAR suppression (Chung et al., 2015). However, it remained unknown whether and how the social behavioral deficits are associated with altered mPFC neural activity in waking-state animals engaged in social interaction. To study the neural abnormalities of the mPFC associated with social dysfunction in IRSp53-KO mice, we herein performed single-unit recordings in freely moving mice engaged in social interactions in a linear social-interaction chamber (Lee et al., 2016). We found that excitatory neurons in the mPFC of IRSp53-KO mice display narrower dynamic ranges of firing rate and reduced burst firing. As a consequence, they showed lower discrimination between social and object targets compared to those of wild-type (WT) control. Our results uncover a novel social coding deficit associated with IRSp53-KO. Results Social impairments in IRSp53-KO mice in the linear-chamber social-interaction test To compare neuronal activities in the mPFC of WT and IRSp53-KO mice during social interaction, we performed single-unit recordings in mice engaged in social interaction in a linear-chamber social-interaction apparatus (Figure 1A). The chamber, a long corridor connected with two side chambers with targets, was designed to measure neuronal activity during social interaction (Lee et al., 2016). A subject mouse was first placed in a separate circular rest box for 5 min for recording of resting neural activity. The mouse was then placed into the linear social-interaction chamber and allowed to explore the chamber with both side chambers being empty (empty-empty/E-E session) for 10 min. This was followed by a session in which one of the side chambers contained a novel social target (S; a conspecific male mouse) and the other contained a novel inanimate object (O) (first S-O session), and another session where the S and O were switched (second S-O session), which was included to control for side (or location)-specific as opposed to target-specific neural activity. The positions of mice in the linear chamber during experiments were determined using the DeepLabCut program (Lauer et al., 2022; Mathis et al., 2018), which automatically marked the subject mouse’s nose, ears, body center, and tail base as well as the social target’s nose and body center (Figure 1B). Sniffing time was defined as the time when the mouse’s nose was within a distance of 3 cm from the front face of the target chamber. In-zone time was defined as the time when the body center (midpoint between the nose and tail base) fell in the area within 9 cm from the front face of the target chamber. Figure 1 with 3 supplements see all Download asset Open asset Social impairments in IRSp53-KO mice in the linear-chamber social-interaction test. (A) Schematic diagram of the linear-chamber social-interaction test used to measure social approach towards a novel conspecific mouse (S, social) versus a novel non-social target (O, object). A tetrode-implanted mouse was first placed in the rest box for 5 min and moved to the linear social-interaction chamber to perform the following three sessions: empty-empty (E–E) session, social-object (first S-O) session, and object-social (second S-O) session. The in-zone area, falling within 9 cm from the front face of the chambers, is indicated by a dashed line. The sniffing zone, falling within 3 cm from the front face of the chambers, is indicated by green, orange, and blue colors. (B) An example video frame of subject mouse and social target mouse body parts automatically tracked by the DeepLabCut program. (C) Schematic (left) and a representative coronal brain section (right) showing the locations of the implanted tetrodes. PrL, prelimbic cortex; IL, infralimbic cortex; Cg1, cingulate cortex, area 1; M2, secondary motor cortex. (D–F) Mean (± standard error of mean/SEM) sniffing duration for left (L) vs. right (R) empty targets during the E-E session (D) and the social (S) vs. object (O) targets during the first S-O (E) and second S-O (F) sessions. (n=6 mice [WT], 8 mice [IRSp53-KO], *P<0.05, ***P<0.001, ns, not significant, two-way repeated-measures (RM)-ANOVA with Sidak’s multiple comparisons test). (G and H) Mean (± SEM) duration of the interaction between subject and social target mice as a function of the distance between the noses of the two mice during the first (G) and second (H) S-O sessions (top). Cumulative duration of proximal and distal social interactions (bottom). (n=47 experiments from 6 mice [WT], 58, 8 [IRSp53-KO], *p<0.05, **p<0.01, ***p<0.001, ns, not significant, two-way RM-ANOVA with Sidak’s multiple comparison test). (I and J) Mean (± SEM) duration of the interaction between subject mice and object target as a function of the distance between the subject mouse’s nose and the center of the object chamber face during the first (I) and second (J) S-O session (top). Cumulative duration of proximal and distal object interactions (bottom). (n=47 experiments from 6 mice [WT], 58, 8 [IRSp53-KO], ***p<0.001, ns, not significant, two-way RM-ANOVA with Sidak’s multiple comparison test). See Supplementary file 2 for statistics. Numerical data used to generate the figure are available in the Figure 1—source data 1. Figure 1—source data 1 Source file for mouse behavior data in Figure 1. The excel file contains the numerical data used to generate Figure 1D–J. https://cdn.elifesciences.org/articles/74998/elife-74998-fig1-data1-v2.xlsx Download elife-74998-fig1-data1-v2.xlsx The single-unit activity was recorded with tetrodes from the prelimbic (PrL), infralimbic (IL), and cingulate cortex (Cg1) regions. Eight tetrodes, four tetrodes in each hemisphere, were implanted into the mPFC and lowered after each round of recording experiment to record neurons at different depths. After the last recording, the locations of all tetrodes were assessed via histology, and data from those falling within the area of interest were used for analysis (Figure 1C, Figure 1—figure supplement 1A). In the E-E session, WT and IRSp53-KO mice showed a preference for neither chamber, as assessed by sniffing and in-zone durations (Figure 1D, Figure 1—figure supplement 2A). In the first S-O session, IRSp53-KO mice spent a comparable amount of time exploring the social and object targets, whereas WT mice displayed a strong preference for the social target (Figure 1E, Figure 1—figure supplement 2B). In the second S-O session, WT mice no longer displayed social preference, likely because of social habituation (Figure 1F, Figure 1—figure supplement 2C). While IRSp53-KO mice showed a decreased number of sniffing visits to the social conspecific mouse, their mean duration of each visit was comparable to that of the WT mice (Figure 1—figure supplement 2D and E). The latter suggests that the impaired social preference is less likely to be caused by genotypic differences in olfactory processing speeds. In fact, a previous report has shown that IRSp53-KO mice display normal olfactory function in the buried food-seeking test (Chung et al., 2015). Moreover, there was no genotype difference in the total distance traveled (Figure 1—figure supplement 2F and G). WT and IRSp53-KO mice displayed a decline in locomotor activity across successive sessions (E-E, first S-O, and second S-O) in each recording experiment (Figure 1—figure supplement 2F), but their overall locomotion remained comparable across the ten experiments (Figure 1—figure supplement 2G). Before comparing the activity of excitatory mPFC neurons during target sniffing, whether the target-interacting behaviors are comparable between genotypes in terms of the proximity to targets was assessed. For social interaction, the distance between the noses of the subject and target mice was examined. Social interactions were divided into proximal and distal according to the nose-to-nose distance (proximal, <2.5 cm; distal, between 2.5 and 10 cm). Total durations of both proximal and distal social interactions were reduced in IRSp53-KO mice during the first, but not second, S-O session (Figure 1G and H). For object interaction, the distance between the subject mouse’s nose and the center of the object chamber face was assessed. There was an increase in the duration of distal but not proximal object interaction in IRSp53-KO mice during the first S-O session, although there was no genotype difference in the second S-O session (Figure 1I and J). In addition, the relative amounts of time spent for proximal versus distal interactions did not vary across genotypes during social or object sniffing (Figure 1—figure supplement 3A and B). These behavioral results collectively indicate that IRSp53-KO mice display social impairments in the linear social-interaction chamber, similar to the social impairments previously determined using the three-chamber test, direct/dyadic social-interaction test, and ultrasonic vocalization test (Chung et al., 2015). Increased resting firing rate in IRSp53-KO pExc mPFC neurons We next compared neuronal firing patterns in the mPFC of WT and IRSp53-KO mice during the abovementioned linear-chamber social-interaction test. To this end, we first analyzed rest-period firing rates in awake and freely moving WT and IRSp53-KO mice. We segregated the neurons into putative excitatory (pExc) and putative inhibitory (pInh) neurons based on their half-valley width (pExc >200ms; pInh <200ms) and peak-to-valley ratio (pExc >1.4; pInh <1.4) (Figure 2A and B). The firing rate of total neurons at rest was higher in the mPFC of IRSp53-KO mice compared with WT mice (Figure 2C). However, only the IRSp53-KO pExc neurons, but not IRSp53-KO pInh neurons, showed a significant increase in firing rate (Figure 2D and E), suggesting that pExc neurons mainly contribute to the increase in the total firing rate. These results differ from those previously obtained from anesthetized IRSp53-KO mice (Chung et al., 2015), which exhibited decreases in total and pExc firing. This highlights the importance of measuring cortical neuronal activity in awake, behaving mice. Figure 2 Download asset Open asset Increased resting firing rate in IRSp53-KO pExc mPFC neurons. (A) Classification of recorded neurons into putative excitatory (pExc) and putative inhibitory (pInh) neurons based on the half-valley width (200ms) and peak-to-valley ratio (1.4). P, peak; V, valley; HVW, half-valley width. (B) Average waveforms of WT and IRSp53-KO pExc (top) and pInh (bottom) neurons (n=366 [WT-pExc], 359 [KO-pExc], 17 [WT-pInh], 24 [KO-pInh]). The waveforms of each neuron were normalized by their peak values. (C–E) Firing rates of WT and IRSp53-KO total (C), pExc (D), and pInh (E) neurons in the mPFC during the 5-min rest period. (n=391 [WT-total], 394 [KO-total], 366 [WT-pExc], 359 [KO-pExc], 17 [WT-pInh], 24 [KO-pInh], ***p<0.001, ns, not significant, Mann-Whitney test). See Supplementary file 2 for statistics. Numerical data used to generate the figure are available in the Figure 2—source data 1. Figure 2—source data 1 Source file for resting firing rate data in Figure 2. The excel file contains the numerical data used to generate Figure 2A–E. https://cdn.elifesciences.org/articles/74998/elife-74998-fig2-data1-v2.xlsx Download elife-74998-fig2-data1-v2.xlsx It should be noted that the majority of recorded neurons were pExc neurons (WT: 366 neurons, 93.6%, IRSp53-KO: 359 neurons, 91.1%), and that relatively few recordings were obtained from pInh neurons (WT: 17 neurons, 4.3%, IRSp53-KO: 24 neurons, 6.1%). Because IRSp53 is expressed primarily in the excitatory pyramidal (not inhibitory) neurons of the cortex (Burette et al., 2014), we hypothesized that the main effects of IRSp53 loss are seen in pExc neurons. Therefore, only pExc neurons were used for further analysis. Of all pExc neurons recorded, only those with a mean firing rate ≥0.5 Hz were included for further analysis in order to avoid low sampling errors arising from the inclusion of neurons with low firing rates (Supplementary file 1). Fewer social-responsive pExc mPFC neurons in IRSp53-KO mice We compared target-dependent mPFC neuronal activity between IRSp53-KO and WT mice to test whether the social behavioral deficit found in IRSp53-KO mice is mirrored in mPFC neuronal activity. For this, we analyzed neuronal activity during the three linear chamber sessions (E-E, first S-O, and second S-O sessions) and determined empty, social, and object target-responsive neurons (termed empty, social, and object neurons hereafter) as those whose firing at the target sniffing zone differed significantly from that in the center zone (Figure 3A; see Methods). Figure 3 with 2 supplements see all Download asset Open asset Fewer social pExc mPFC neurons in IRSp53-KO mice. (A) Distributions of instantaneous firing rates (FR) during social sniffing and center zone (top) and the receiver operating characteristic curves (ROCs; bottom) of increasing (left) and decreasing (right) social neuron examples. (B) Average spike density functions (SDFs) of firing rate responses to empty (green), social (orange), and object (blue) targets (aligned to the onset of sniffing) for all social (S) neurons. Social neurons are divided by genotype (WT left, IRSp53-KO right) and response direction (increasing (+) top, decreasing (-) bottom). Total numbers of neurons are indicated at the upper right corner of each SDF. Shading indicates ± SEM. (C and D) Proportions of total social (C) and object (D) neurons (both increasing and decreasing neurons) out of the total recorded neurons. (*p<0.05, ns, not significant, Fisher’s exact test). (E) Venn diagram summary of empty (E), social (S), and object (O) neuronal proportions for WT (left) and IRSp53-KO (right) pExc neurons. Numbers indicate neuronal proportion % (n neurons). See Supplementary file 2 for statistics. In order to determine whether the classified social, object, and empty neurons increase or decrease their firing rates upon target sniffing, we generated the average spike density functions (SDFs) for WT and IRSp53-KO target neurons. We found both increasing and decreasing target neurons (i.e., those increasing and decreasing their firing rates upon target sniffing onset, respectively) in WT as well as IRSp53-KO mice (Figure 3B, Figure 3—figure supplement 1A and B). A significantly lower proportion was classified as social neurons among IRSp53-KO pExc neurons compared to WT pExc neurons (Figure 3C). Meanwhile, the proportions of object and empty neurons were comparable between genotypes (Figure 3D, Figure 3—figure supplement 1C). The numbers of target neurons were summarized in Venn diagrams (Figure 3E). Reduction in social/non-social neuronal proportion in mPFC is a phenomenon that is shared by several autism mouse models, such as Shank2-KO (Lee et al., 2021a) and Cntnap2-KO mice (Levy et al., 2019), and therefore, may be causally related to the social impairment seen in IRSp53-KO mice. Robust target-dependent responses of pExc mPFC neurons We then tested whether the classified target neurons respond consistently to specific targets across sessions and across trials. The firing responses of WT and IRSp53-KO mPFC pExc neurons to social, object, and sidedness were consistent across the first and second S-O sessions, as indicated by positively correlated z-scores across the two sessions (Figure 3—figure supplement 2A–D). When we compared the response magnitude of neurons concerning the proximity to targets, both WT and IRSp53-KO neurons showed significantly higher response magnitudes during proximal than distal interactions with social and object targets (Figure 3—figure supplement 2E and F). In addition, social neurons in the mPFC do not respond to all social interactions but rather display ‘trial-to-trial stochasticity’ (Liang et al., 2018). This stochasticity was also present in the increasing and decreasing social neurons in the WT and IRSp53-KO mPFC (Figure 3—figure supplement 2G). Both WT and IRSp53-KO target neurons displayed trial consistencies that are higher than 50%, which corroborates that the responses of social and object neurons to the targets do not occur by chance. Although the proportion of mPFC social neurons was reduced in IRSp53-KO mice, their consistencies in firing rate responses to proximal target interactions were comparable to that in WT mice (Figure 3—figure supplement 2H1). Limited social versus object firing-rate discriminability in IRSp53-KO pExc mPFC neurons To test whether the firing-rate discriminability between social and object targets may also be limited in IRSp53-KO neurons, we compared social- versus object-target in-zone firing rates. The slopes of linear regression and the degrees of dispersion (indicated by 95% confidence interval) for the left versus right (L vs. R) in-zone firing rates in the E-E session were comparable between genotypes (Figure 4A). In contrast, the slopes of the linear regression lines relating social and object (S vs. O) firing rates were biased towards the social firing rate in both genotypes in the first and second S-O sessions, indicating preferential responses to social to object targets (Figure 4B, Figure 4—figure supplement 1A). Additionally, the confidence interval tended to be narrower for IRSp53-KO pExc neurons, especially in the first S-O session, compared to WT pExc neurons for the S versus O firing rates, suggestive of limited discriminability (Figure 4B). Consistently, the absolute difference in firing rate for S versus O (an indication of discriminability) in the first S-O session was significantly lower in IRSp53-KO pExc neurons than WT pExc neurons (Figure 4C). Nevertheless, IRSp53-KO pExc neurons could still discriminate between social and object targets significantly better compared to the left versus right side discrimination in the E-E session (Figure 4C). This result suggests that IRSp53-KO mice have the ability to recognize social and object stimuli, albeit in a reduced degree than WT mice. Figure 4 with 2 supplements see all Download asset Open asset Limited discriminability between social and object targets in IRSp53-KO pExc mPFC neurons. (A and B) Scatterplot of left in-zone firing rate (FRL) against right in-zone firing rate (FRR) during the E-E session (A) and social in-zone firing rate (FRS) against object in-zone firing rate (FRO) during the first S-O session (B) for WT and IRSp53-KO pExc neurons. Solid lines indicate simple linear regressions for WT (black) and KO (red) neurons. Shaded areas indicate the 95% confidence intervals for the WT (black) and KO (red) firing rates. Blue dashed lines are 45 degree lines. (n=233 [WT-pExc] and 258 [KO-pExc]), **p<0.01, ns, not significant, simple linear regression with slope comparison test (see Methods). (C) Absolute changes in left versus right in-zone firing rates (E-E session) and social versus object in-zone firing rates (first (fS-O) and second (sS-O) S-O sessions) for WT and IRSp53-KO pExc neurons. (n=233 [WT-pExc] and 258 [KO-pExc], *p<0.05, **p<0.01, ***p<0.001, ns, not significant, two-way RM-ANOVA with Sidak’s test). (D and E) Neural decoding of left versus right sidedness during the E-E session (D) and social versus object target during the first S-O session (E) as a function of ensemble size (left) and their decoding performance at maximum comparable ensemble size (indicated by blue dashed line) (right). Ensemble sizes vary due to the limitation of sniffing trials in some experiments (minimum trial number for the SVM decoding was set to 10 per target). Note that the decoding accuracies of WT (pink) and KO (grey) neurons remain similar to chance level (50%) across all tested ensemble sizes after target shuffling. (n=100 decoding trials for 170 and 109 pExc neurons in the E-E and first S-O sessions, respectively [WT] and 100, 158, 58 [KO], ***p<0.001, ns, not significant, Mann-Whitney test). See Supplementary file 2 for statistics. Numerical data used to generate the figure are available in the Figure 4—source data 1. Figure 4—source data 1 Source file for firing-rate discriminability data in Figure 4. The excel file contains the numerical data used to generate Figure 4A–E. https://cdn.elifesciences.org/articles/74998/elife-74998-fig4-data1-v2.xlsx Download elife-74998-fig4-data1-v2.xlsx We next performed both single cell and ensemble decoding analyses using the support vector machine to further assess the ability of neurons to discriminate between social and object targets. The decoding performances of individual neurons and neuronal population were both comparable between genotypes for left versus right sidedness discriminability in the E-E session (Figure 4D, Figure 4—figure supplement 1B). In contrast, these decoding performances were significantly lower in IRSp53-KO neurons for social versus object target discriminability in the first S-O session (Figure 4E, Figure 4—figure supplement 1C). In the second S-O session, although the individual neurons’ decoding performances were comparable between genotypes, population decoding performances were significantly poorer in IRSp53-KO than WT neurons (Figure 4—figure supplement 1D and E). Moreover, we examined whether the discriminability between social and object targets is affected by the proximity to the target. Although the discriminability was generally greater during proximal interaction compared to distal interaction, the discriminability in KO neurons was lower in both proximal and distal conditions compared to that in WT neurons in the first S-O session (Figure 4—figure supplement 2A and B). However, the discriminability was no longer different between genotypes during the distal social condition in the second S-O session (Figure 4—figure supplement 2C and D). These results collectively suggest weakened social versus object discriminability in IRSp53-KO pExc mPFC neurons at both individual neuronal and population levels. Limited firing-rate range and variability of IRSp53-KO pExc mPFC neurons The pExc mPFC neurons of IRSp53-KO mice showed significantly higher mean firing rates than those of WT mice during the initial 5-min rest period (Figure 2D), but comparable mean firing rates during the 30 min linear chamber test period (Figure 5B). However, we noticed in our preliminary analysis that temporal profiles of instantaneous firing rate (3 s time-bin advanced in 1 s steps) differ substantially between WT and IRSp53-KO neurons during the 30 min linear chamber test, as shown by representative examples in Figure 5A. Figure 5 with 2 supplements see all Download asset Open asset Limited firing-rate range and variability in IRSp53-KO pExc mPFC neurons during linear chamber exploration. (A) Instantaneous firing-rate traces of representative WT (top) and IRSp53-KO (bottom) pExc neurons (3 s window advanced in 1 s steps) during a sample linear chamber experiment (30 min). Solid horizontal lines indicate the overall mean firing rates (μ). Shaded regions indicate one standard deviation (σ, sigma). (B) Mean firing rate of WT and IRSp53-KO pExc neurons during the 30 min linear chamber test. (n=233 [WT-pExc] and 258 [KO-pExc], ns, not significant, Mann-Whitney test). (C) Firing-rate ranges (maximum – minimum instantaneous firing rate) of WT and IRSp53-KO pExc neurons during the linear chamber test (n=233 [WT-pExc] and 258 [KO-pExc], **p<0.01, Mann-Whitney test). (D) Mean (± SEM) histograms of normalized instantaneous firing rate during the linear chamber test. For each neuron, instantaneous firing rates were normalized by its maximum instantaneous firing rates. (n=233 [WT-pExc] and 258 [KO-pExc], **p<0.01, ***p<0.001, ns, not significant, two-way RM-ANOVA with Bonferroni’s multiple comparisons test). (E) Sigma values of the instantaneous firing rates of WT and IRSp53-KO pExc neurons during the linear chamber test. (n=233 [WT-pExc] and 258 [KO-pExc], *p<0.05, Mann-Whitney test). (F) Log-scale scatter plot of sigma values against mean firing rates of WT and IRSp53-KO pExc neurons during the linear chamber test. Solid lines indicate simple linear regression of WT (black) and KO (red) values. (n=233 [WT-pExc] and 258 [KO-pExc], ***p<0.001, ns, not significant, slope comparison test (see Methods)). (G) Sigma values for the instantaneous firing rates of WT (left) and IRSp53-KO (right) pExc neurons during the E-E, first S-O (fS-O), and second S-O (sS-O) sessions of the linear chamber test. (n=233 [WT-pExc] and 258 [KO-pExc], *p<0.05, ns, not significant, Friedman test followed by Dunn’s multiple comparisons test). See Supplementary file 2 for statistics. Numerical data used to generate the figure are available in the Figure 5—source data 1. Figure 5—source data 1 Source file for instantaneous firing rate data in Figure 5. The excel file contains the numerical data used to generate Figure 5A–G. https://cdn.elifesciences.org/articles/74998/elife-74998-fig5-data1-v2.xlsx Download elife-74998-fig5-data1-v2.xlsx Further examinations of instantaneous firing rate revealed that the maximum instantaneous firing rate during the linear" @default.
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W4313012224 title "Decision letter: Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice" @default.
W4313012224 doi "https://doi.org/10.7554/elife.74998.sa1" @default.
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