Cited by 54Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeural dynamics and brain function

Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats

Open access
Bijlsma, Ate, Omrani, Azar, Spoelder, Marcia, Verharen, Jeroen P.H., Bauer, Lisa, Cornelis, Cosette, de Zwart, Beleke, van Dorland, René +2 more·2022·The Journal of Neuroscience

Abstract

Sensory driven activity during early life is critical for setting up the proper connectivity of the sensory cortices. We ask here whether social play behavior, a particular form of social interaction that is highly abundant during postweaning development, is equally important for setting up connections in the developing prefrontal cortex (PFC). Young male rats were deprived from social play with peers during the period in life when social play behavior normally peaks [postnatal day 21–42] (SPD rats), followed by resocialization until adulthood. We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected. This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells. In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning (PRL) task, which depends on the integrity of the PFC, by using a more simplified cognitive strategy than controls. Interestingly, we observed that one daily hour of play during SPD partially rescued the behavioral performance in the PRL, but did not prevent the decrease in PFC inhibitory synaptic inputs. Our data demonstrate the importance of unrestricted social play for the development of inhibitory synapses in the PFC and cognitive skills in adulthood and show that specific synaptic alterations in the PFC can result in a complex behavioral outcome. SIGNIFICANCE STATEMENT This study addressed the question whether social play behavior in juvenile rats contributes to functional development of the prefrontal cortex (PFC). We found that rats that had been deprived from juvenile social play (social play deprivation - SPD) showed a reduction in inhibitory synapses in the PFC and a simplified strategy to solve a complex behavioral task in adulthood. Providing one daily hour of play during SPD partially rescued the cognitive skills in these rats, but did not prevent the reduction in PFC inhibitory synapses. Our results demonstrate a key role for unrestricted juvenile social play in PFC development and emphasize the complex relation between PFC circuit connectivity and cognitive function.

AI snapshot

Written from the paper’s full text.

TL;DR

Social play deprivation in male rats from postnatal day 21–42 caused a lasting reduction in prefrontal inhibitory synapses onto layer 5 pyramidal cells and altered probabilistic reversal learning in adulthood. One hour of daily play partially rescued cognitive performance but did not prevent the reduction in prefrontal inhibition.

Key findings

  • Adult SPD rats had reduced inhibitory synaptic currents in medial PFC L5 pyramidal cells: sIPSC frequency and amplitude were lower (p = 0.002 and p = 0.03), mIPSC frequency was lower (p < 0.0005), and mIPSC rise time was increased (p = 0.0008), while sEPSCs were unaffected (p = 0.27 and p = 0.35).
  • Immunohistochemistry showed lower perisomatic PV synapse density in SPD tissue (p = 0.02) and lower PV and CB1-R puncta intensity (p < 0.0005 and p = 0.02), with no change in VGAT puncta density (p = 0.19) or GAD67/PV cell density.
  • In probabilistic reversal learning, SPD rats completed more reversals (p = 0.001), made more correct choices (p = 0.032), and showed more win-stay behavior (p = 0.001) than controls in batch 1; pooled data confirmed more reversals in SPD (p < 0.001).
  • SPD1h rats showed partial behavioral rescue: pooled win-stay responses differed from SPD (p = 0.03) but not from controls (p = 0.97), yet mIPSC frequency remained reduced in SPD1h versus control slices (p = 0.017; SPD vs SPD1h p = 0.99).

Methods

  • Male Lister Hooded rats were assigned to control, social play deprivation (SPD; divider-separated littermates P21–P42), or SPD1h (same but 1 h/day social interaction). After P42, all were pair-housed until adulthood.
  • Adult rats underwent probabilistic reversal learning in operant chambers, with trial-by-trial analysis and computational modeling of eight models using AIC and Bayesian model selection.
  • Whole-cell patch-clamp recordings were made from medial PFC layer 5 pyramidal neurons to measure sIPSCs, mIPSCs, and sEPSCs; immunohistochemistry quantified GAD67/PV cell density and perisomatic VGAT, PV, and CB1-R puncta.

Limitations

  • The paper states that it is unclear whether reduced inhibitory drive to L5 cells enhances downstream activity or compensates for upstream/local network changes, and that the aspects of play driving PFC development remain speculative.
  • The paper notes that the partial behavioral rescue in SPD1h rats likely involves compensatory changes other than L5 inhibition, requiring further study.
  • Evident from the text: only male rats were studied; electrophysiology was conducted in two batches with different protocols and researchers, requiring normalization and pooling; sample sizes were modest (e.g., 6 rats per group for immunohistochemistry, 12 per group in behavioral batches).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.0524-22.2022

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

25 of 66 cited sources checked · 15 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    During the period when the PFC matures (between weaning and early adulthood), young animals display an abundance of social play behavior.

    “Importantly, during the period when the PFC matures, i.e., in between weaning and early adulthood (Kolb et al., 2012), young animals display an abundance of an energetic form of social behavior known as social play behavior (Panksepp et al., 1984;Vanderschuren et al., 1997;Pellis and Pellis, 2009).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Kolb et al., 2012 source
    • cites Panksepp et al., 1984 source
    • cites Vanderschuren et al., 1997 source
  • Interpretationcitation

    The simplified strategy is probably cognitively less demanding.

    “This is probably cognitively less demanding (Christie and Schrater, 2015)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Christie and Schrater, 2015 source
  • Findingown data

    In adult rats deprived of social play P21-42, spontaneous excitatory synaptic currents in L5 mPFC are unaffected.

    “We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected.”
    • Also stated in: § Results · plain
      “By contrast, spontaneous EPSCs (sEPSCs) were unaffected (Fig. 1F,G).”
    Quote in the paperSubstantial claim
  • Findingown data

    In adult rats deprived of social play P21-42, spontaneous inhibitory synaptic currents in L5 mPFC are reduced.

    “We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected.”
    • Also stated in: § Results · plain
      “We found that the frequency and amplitude of spontaneous IPSCs (sIPSCs) was reduced in SPD rats (Fig. 1D,E).”
    Quote in the paperSubstantial claim
  • Findingown data

    Adult SPD rats achieve more reversals in a PRL task than controls.

    “In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning (PRL) task, which depends on the integrity of the PFC, by using a more simplified cognitive strategy than controls.”
    • Also stated in: § Results · plain
      “Remarkably, SPD rats completed more reversals (Fig. 5D) and made more correct choices (Fig. 5E) compared with CTL rats.”
    • Also stated in: § Results · boosted
      “However, when we normalized and pooled the data from both batches, the number of reversals in the SPD group was clearly above CTL (p , 0.001; two-way ANOVA with Tukey's post hoc test).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 29
  • May combine two claims. 17
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim.

    Premisecitation

    How experience-dependent plasticity contributes to the development of other brain structures such as the PFC remains largely unknown.

    “However, how experience-dependent plasticity contributes to the development of other brain structures, such as the prefrontal cortex (PFC), remains largely unknown (Kolb et al., 2012;Larsen and Luna, 2018;Reh et al., 2020).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Kolb et al., 2012 source

      The Sensory and Motor Experience section says it is not yet known whether common factors or multiple mechanisms drive experience-related synaptic changes in the PFC. That supports uncertainty about how the changes occur. But the Factors Influencing Prefrontal Development section reviews established effects of experience on PFC development, so the broader claim that its contribution remains largely unknown overstates the source. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites Larsen and Luna, 2018 source
    • cites Reh et al., 2020 source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sensory deprivation during development causes long-lasting deficits in sensory processing resulting from improper synaptic wiring.

    “This process has been extensively studied in the sensory cortices, and it is long known that sensory deprivation during development causes long-lasting deficits in sensory processing resulting from improper synaptic wiring (Hensch, 2005;Gainey and Feldman, 2017).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hensch, 2005 source
    • cites Gainey and Feldman, 2017 source

      Section 3 reports that deprivation during the visual critical period can rapidly remove inhibitory synapses and precede a loss of visual-evoked spiking. It does not establish that developmental deprivation causes long-lasting sensory-processing deficits or that improper synaptic wiring causes those deficits; the Conclusion instead discusses short-term changes and subsequent recovery of firing rates. No page numbers are available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Sensory deprivation induces specific alterations in inhibitory neurotransmission that affect adult sensory processing.

    “It is well described that sensory deprivation induces specific alterations in inhibitory neurotransmission that affect adult sensory processing (Turrigiano and Nelson, 2004;Hensch, 2005;Rupert and Shea, 2022).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Turrigiano and Nelson, 2004 source
    • cites Hensch, 2005 source
    • cites Rupert and Shea, 2022 source
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Perisomatic synapses are made by PV and CCK basket cells, of which only the latter express CB1-R.

    “Perisomatic synapses are made by parvalbumin (PV) and cholecystokinin (CCK) basket cells (Whissell et al., 2015), of which only the latter express the cannabinoid receptor 1 (CB1-R; Katona et al., 1999).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Whissell et al., 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Katona et al., 1999 source

      The section on CB1 expression in hippocampal basket cells and Table 1 show that CB1 is present in nearly all CCK-positive cells, supporting the main distinction. But Table 1 also reports CB1 in 6 of 130 PV-positive cells (4.6%), so the absolute claim that only CCK basket cells express it is not supported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim.

    Premisecitation

    The PFC-dependent PRL task depends on the integrity of the PFC.

    “In order to assess the impact of SPD on cognitive flexibility, a PFC-dependent probabilistic reversal learning (PRL) task was used (Fig. 5A,B; Dalton et al., 2016;Verharen et al., 2020).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites Dalton et al., 2016 source
    • cites Verharen et al., 2020 source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A direct link between PFC PV cell activity and social behavior was recently demonstrated.

    “a direct link between PFC PV cell activity and social behavior was recently demonstrated (Bicks et al., 2020;Sun et al., 2020).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Bicks et al., 2020 source
    • cites Sun et al., 2020 source
  • Classified as probably not a substantial claim.

    Premisecitation

    A reduction in PFC inhibition has previously been linked to impaired cognitive flexibility.

    “A reduction in PFC inhibition has previously been linked to impaired cognitive flexibility (Gruber et al., 2010)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Gruber et al., 2010 source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Alterations in PV cells during development shape cognitive capacities in adulthood.

    “Alterations in PV cells during development are shown to shape cognitive capacities in adulthood”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Donato et al., 2015 source
    • cites Mukherjee et al., 2019 source
    • cites Canetta et al., 2022 source
  • Classified as probably not a substantial claim.

    Premisecitation

    Changes in PFC network activity directly affect cognitive and social skills.

    “Changes in PFC network activity directly affect cognitive and social skills”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites Yizhar et al., 2011 source
    • cites Dalton et al., 2016 source

      The lOFC inactivation results report impaired probabilistic reversal learning in rats, supporting an effect of prefrontal activity on a specific cognitive ability. The paper does not establish effects on social skills or make a general claim about PFC network activity. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites Verharen et al., 2020 source

      The Discussion (page unavailable) reports that inactivating several rat PFC subregions impaired probabilistic reversal learning, supporting an effect on a specific cognitive process. It does not report effects on social skills, and its findings about rat PFC subregions do not establish the broader claim about PFC network activity. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim.

    Premisecitation

    A similar increase in reversals was reported after prelimbic mPFC inactivation.

    “A similar increase in reversals was also reported after prelimbic mPFC inactivation (Dalton et al., 2016)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Dalton et al., 2016 source
  • May combine two claims.

    Interpretationcitation

    Reduced PV and CB1 expression may indicate a reduced activity level in PV cells and an altered endocannabinoid tone.

    “This may indicate a reduced activity level in PV cells (Donato et al., 2013;Caballero et al., 2014) and an altered endocannabinoid tone”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Donato et al., 2013 source
    • cites Caballero et al., 2014 source
    • cites Sciolino et al., 2010 source
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    PRL performance depends on complex interactions between several component processes, including sensitivity to positive and negative feedback, response persistence, and exploration versus exploitation, each requiring functional activity in distinct PFC regions and brain regions outside the PFC.

    “PRL performance depends on complex interactions between several component processes, including the sensitivity to positive and negative feedback, response persistence and exploration versus exploitation, each of which requires functional activity in distinct PFC regions (Verharen et al., 2018(Verharen et al., , 2020)), as well as brain regions outside the PFC (Izquierdo et al., 2017).”
    Quote in the paperNot a substantial claim3 of 3 sources checked
    • cites Verharen et al., 2018 source

      Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites Verharen et al., 2020 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites Izquierdo et al., 2017 source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous observations in sensory cortex show a reduction in inhibition after sensory deprivation.

    “in line with previous observations in sensory cortex showing a reduction in inhibition after sensory deprivation”
    Quote in the paperNot a substantial claim2 of 3 sources checked
    • cites Hensch et al., 1998 source

      The main text (Fig. 1) reports reduced GABA release in GAD65-deficient mice, while the monocular-deprivation results (Fig. 3) report changes in eye responsiveness. Neither passage reports that sensory deprivation itself reduces inhibition in sensory cortex. Searches for reduced inhibition after deprivation found no such observation in our copy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
    • cites Morales et al., 2002 source
    • cites Chattopadhyaya et al., 2004 source
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Play is not displayed continuously by young rats, but appears in peaks of relatively short duration across the day.

    “Play is not displayed continuously by young rats, but appears in peaks of relatively short duration across the day (Melotti et al., 2014;Lampe et al., 2019).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Melotti et al., 2014 source

      In “Relationships Between Home Cage Social Play and Other Play Contexts” (page not provided), the paper reports that 93.7% of the social play observed during the first hour of darkness occurred in its first 30 minutes. This supports a brief concentration of play rather than continuous play during that observation period, but the study did not observe play across the day or establish multiple daily peaks. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites Lampe et al., 2019 source

      The Methods section (‘Home cage play observations’) says pilot observations found short play peaks interspersed across the first four hours of the dark phase. This supports intermittent, short-duration play, but not the claim that peaks occur across the day as a whole. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • May combine two claims.

    Findingown data

    Rats in the SPD and CTL groups readily acquired the PRL task and achieved a comparable performance level in terms of rewards obtained.

    “Rats in the SPD and CTL groups readily acquired the task and achieved a comparable performance level in terms of rewards obtained (Fig. 5C).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    SPD1h rats' performance in reversal completion resembled the SPD group during initial sessions but was closer to the control group in later sessions.

    “the SPD1h rats resembled the SPD group during the initial sessions, but performed closer to the control group in later sessions (Fig. 7B)”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    In all groups, Q learning models were generally better than heuristic win-stay models at describing behavioral choices.

    “Although in all groups Q learning models (models 5-8) were generally better than the heuristic win-stay models (models 2 and 3) to describe behavioral choices”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    When data from both batches were pooled, the difference between SPD and SPD1h groups was even clearer.

    “This difference between SPD and SPD1h group was even clearer when we pooled the data from both batches (Fig. 7E,F).”
    Quote in the paperNot a substantial claim
  • The quote only partly states this claim.

    Findingown data

    The SPD group had a clear reduction in mIPSC frequency compared with CTL rats, about 30%.

    “a clear reduction in mIPSC frequency was found in the SPD group compared with CTL rats (Fig. 9B).”
    • Also stated in: § Discussion · plain
      “We found a ;30% reduction in mIPSC frequency”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Puncta size is not much affected in SPD tissue.

    “Puncta size was not much affected, although synaptic CB1-R puncta were slightly larger in SPD tissue (Fig. 4E).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    The SPD1h win-stay curve resembled the SPD curve in some earlier sessions but remained closer to the CTL curve toward later sessions.

    “The SPD1h curve resembled the SPD curve in some of the earlier sessions, but then remained closer to the CTL curve toward the later sessions.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    SPD1h rats made ~200 pins and ~300 pounces per hour.

    “SPD1h rats made ;200 pins and ;300 pounces per hour, which was comparable to rats in other studies that were isolated for 24 h (Niesink and Van Ree, 1989;Vanderschuren et al., 1995aVanderschuren et al., , b, 2008;;Achterberg et al., 2016).”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Rats of all three groups learned the PRL task equally well and gained similar numbers of rewards.

    “Rats of all three groups learned the task equally well and gained similar numbers of rewards (Fig. 7A).”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    In the second batch, SPD rats tended to complete more reversals per session than CTL rats, but this difference did not reach statistical significance.

    “Consistent with our earlier results (Fig. 5D), SPD rats tended to complete more reversals per session than CTL rats (Fig. 7B), but this difference did not reach statistical significance.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Synaptic CB1-R puncta are slightly larger in SPD tissue.

    “Puncta size was not much affected, although synaptic CB1-R puncta were slightly larger in SPD tissue (Fig. 4E).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Synaptic density is not correlated with cell size.

    “We verified that somata of L5 pyramidal cells had similar size in SPD and CTL tissue (Fig. 4F) and synaptic density was not correlated with cell size (Fig. 4G).”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    The PFC is important for neural operations required during social interactions.

    “The PFC is important for higher cognitive, so-called executive functions (Miller and Cohen, 2001;Floresco et al., 2008), as well as neural operations required during social interactions (Frith and Frith, 2012;Rilling and Sanfey, 2011).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Frith and Frith, 2012 source
    • cites Rilling and Sanfey, 2011 source
  • Classified as probably not a substantial claim.

    Premisecitation

    The PFC is important for higher cognitive executive functions.

    “The PFC is important for higher cognitive, so-called executive functions (Miller and Cohen, 2001;Floresco et al., 2008), as well as neural operations required during social interactions (Frith and Frith, 2012;Rilling and Sanfey, 2011).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Miller and Cohen, 2001 source
    • cites Floresco et al., 2008 source
  • May combine two claims.

    Interpretationown data

    SPD rats, with or without daily playtimes, switched from a learning-based strategy to a more perseverative strategy, whereas CTL rats continued learning throughout training.

    “Thus, SPD rats, with or without daily playtimes, switched from a learning-based strategy to a more perseverative strategy, whereas CTL rats continued learning throughout training.”
    • Also stated in: § Discussion · plain
      “In this study, we observed that adult rats which had experienced SPD displayed a different behavioral strategy in the PRL task compared with CTL animals.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    L5 pyramidal cells are the main output neurons of the PFC.

    “We chose to study L5 cells, because these are the main output neurons of the PFC (Douglas and Martin, 2004).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Douglas and Martin, 2004 source
  • Classified as probably not a substantial claim.

    Premisecitation

    Behavioral performance after social isolation can be partially rescued by allowing the rats daily play for a short amount of time.

    “Early behavioral studies have shown that behavioral performance after social isolation can be partially rescued by allowing the rats daily play for a short amount of time (Einon et al., 1978;Potegal and Einon, 1989).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Einon et al., 1978 source
    • cites Potegal and Einon, 1989 source
  • May combine two claims.

    Interpretationown data

    Daily playtimes during the play deprivation period did not affect the development of PFC inhibition and failed to rescue the reduction in PFC GABAergic synapses.

    “indicating that daily playtimes during the play deprivation period did not affect the development of PFC inhibition (Fig. 9B).”
    • Also stated in: § Results · plain
      “The inclusion of daily play sessions during the SPD period failed to rescue the reduction in PFC GABAergic synapses”
    • Also stated in: § Discussion · plain
      “We observed that 1 h of daily playtime during the deprivation period could not rescue the reduction in prefrontal IPSCs”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Study design and conductnone given

    We verified that our conclusions were supported by each batch separately.

    “We verified that our conclusions were supported by each batch separately.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Detected currents were manually inspected to exclude false events.

    “The detected currents were manually inspected to exclude false events.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The investigator was blinded to the groups of the sections when acquiring the images and performing the quantifications.

    “The investigator was blinded to the groups of the sections when acquiring the images and performing the quantifications.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Series resistance was constantly monitored, and cells were rejected from analysis if series resistance changed by >20% or exceeded 30 MΩ.

    “Series resistance was constantly monitored, and the cells were rejected from analysis if the series resistance changed by .20% or exceeded 30 MX.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Study design and conductown data

    In the electrophysiology and immunocytochemistry datasets, the variance between cells or ROIs within slices was larger than the variance between slices, indicating that individual cells and ROIs can be treated as independent measurements.

    “In the electrophysiology and immunocytochemistry datasets the variance between cells or regions of interest (ROIs) within slices was larger than the variance between slices, indicating that individual cells and ROIs can be treated as independent measurements.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pinning and pouncing are the most characteristic parameters of social play behavior in rats.

    “Of these behaviors, pinning and pouncing are considered the most characteristic parameters of social play behavior in rats (Panksepp and Beatty, 1980;Vanderschuren et al., 1995b).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Panksepp and Beatty, 1980 source
    • cites Vanderschuren et al., 1995b

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    SPD results in a decrease in inhibitory synaptic input to L5 pyramidal cells in the adult PFC, with differential effects on perisomatic PV and CB1-R synapses.

    “Together, these data show that SPD results in a decrease in inhibitory synaptic input to L5 pyramidal cells in the adult PFC, with differential effects on perisomatic PV and CB1-R synapses.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    Unrestricted juvenile social play is crucial to instruct the development of specific inhibitory connections in the PFC and to shape adaptive cognitive strategies in the adult brain.

    “Our data therefore suggest that the experience of unrestricted juvenile social play is crucial to instruct the development of specific inhibitory connections in the PFC and to shape adaptive cognitive strategies in the adult brain.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    Social play behavior is of critical importance for the development of PFC circuitry and function, and PFC-dependent cognitive processes.

    “Our data demonstrate that social play behavior is of critical importance for the development of PFC circuitry and function, and PFC-dependent cognitive processes.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    Juvenile social play has a key role in the development of perisomatic inhibition in the PFC and PFC-dependent cognitive flexibility.

    “Together, our results demonstrate a key role for juvenile social play in the development of perisomatic inhibition in the PFC and PFC-dependent cognitive flexibility.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The simplified strategy may be preferred under certain conditions, especially if it does not lead to a reduction in reward.

    “and may therefore be preferred under certain conditions, especially if this does not lead to a reduction in reward.”
    Quote in the paperNot a substantial claim
43 of 43
  • The paper relies on this without support.

    The developmental changes in PFC circuitry that facilitate cognitive skills are incompletely understood.

    “The developmental changes in the PFC circuitry that facilitate these cognitive skills are incompletely understood.”
  • The paper relies on this without support.

    The cellular mechanisms by which social play facilitates PFC development remain elusive.

    “However, the cellular mechanisms by which social play facilitates PFC development remain elusive.”
  • The paper relies on this without support.

    A daily limited, but condensed play time should be sufficient to prevent neural and behavioral changes.

    “The idea behind these studies was that a daily limited, but condensed play time should be sufficient to prevent neural and behavioral changes.”
  • The authors state this as an assumption.

    The random choice model's assumption that animals choose randomly is valid for the computational modeling.

    “The random choice model is the null model, which assumes that animals choose randomly [i.e., p = 0.5 for each choice, so that the log likelihood is given by [number of trials]*log(0.5)].”
  • The authors state this as an assumption.

    Choice behavior in the computational models follows a Softmax function.

    “In all models (except for the random choice model), choice was modeled using a Softmax equation, such that the probability of choosing the left lever in trial t was given by:”
  • The authors state this as an assumption.

    Lever values are updated according to a Q learning rule.

    “After each trial outcome, lever values Q left and Q right were updated according to a Q learning rule:”
  • The paper relies on this without support.

    1 h of daily condensed play is roughly equivalent to 4-6 h of normal play.

    “although 1 h of daily condensed play (roughly equivalent to 4-6 h of”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Deprivation of social play leads to long-lasting impairments in the social, emotional and cognitive domain.

    “previous studies have shown that deprivation of social play leads to long-lasting impairments in the social, emotional and cognitive domain (Baarendse et al. 2013; Bijlsma et al. 2022; Lukkes et al. 2009a; Potegal and Einon 1989; Van den Berg et al. 1999a; Whitaker et al. 2013, for reviews see Vanderschuren and Trezza 2014; Pellis et al. 2023).”

    From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Bijlsma et al. 2022

    The Discussion (page not available) reports that juvenile social-play deprivation affected cognition in adult rats even after weeks of unrestricted social interaction, supporting a long-lasting cognitive effect. It does not report lasting social or emotional impairments; it describes those skills as possible benefits of play rather than measured outcomes of this study. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting ages for the electrophysiology experiments

    Minor

    The Results place the adult experiments at postnatal weeks 8-10 and immediately describe voltage-clamp recordings, but the Methods state that rats were 12-15 weeks old when slices were prepared for those recordings.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Paxinos G , Watson C (2007) The rat brain in stereotaxic coordinates, Ed 6. San Diego: Academic Press Inc.

Cited by

Sorted by citations

Authors
Bijlsma, A., Omrani, A., Spoelder, M., Verharen, J. P. H., Bauer, L., Cornelis, C., de Zwart, B., van Dorland, R., Vanderschuren, L. J. M. J., & Wierenga, C. J.
Affiliations
Utrecht University (NL)
Venue
The Journal of Neuroscience
Published
2022-10-17
Volume
42
Issue
46
Pages
8716-8728
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W4306632238
Cited by
54
References
76
Citations by year
2026: 8 · 2025: 14 · 2024: 16 · 2023: 16
FWCI
4.30
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
  • Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALWOP.2015.105)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
social play, prefrontal cortex development, inhibitory synapses, cognitive flexibility, parvalbumin interneurons, probabilistic reversal learning, medial prefrontal cortex, synaptic currents, postnatal development, cognitive strategies
MeSH terms
Animals, Cognition, Male, Parvalbumins, Synapses, Prefrontal Cortex, Rats, Neurogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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