Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats
Open accessAbstract
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.
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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
Cites
Statistics
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 - 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 - Also stated in: § Results · plain
- 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 - Also stated in: § Results · plain
- 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 - Also stated in: § Results · plain
- Findingown data
The reduction in mIPSC frequency was similar in SPD and SPD1h slices.
“This reduction was similar in the SPD and SPD1h slices”
- Also stated in: § Discussion · plain
“while their reduction in mPFC inhibition was similar to SPD rats”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
The density of PV synapses (colocalizing with VGAT) is significantly lower in SPD tissue compared with CTL tissue.
“The density of VGAT puncta was not different in SPD and CTL tissue, but the density of PV synapses (colocalizing with VGAT) was significantly lower in SPD tissue compared with CTL tissue (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
SPD rats made more correct choices compared with CTL rats.
“Remarkably, SPD rats completed more reversals (Fig. 5D) and made more correct choices (Fig. 5E) compared with CTL rats.”
- Also stated in: § Results · plain
“In addition, we observed that SPD rats made more correct choices compared with CTL rats (Fig. 7C), establishing an important independent confirmation of our earlier results (Fig. 5E).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
VGAT puncta intensity is similar in SPD and CTL tissue.
“This reduction was specific as VGAT puncta intensity was similar in SPD and CTL tissue (Fig. 4D).”
Quote in the paperSubstantial claim - Findingown data
Synaptic PV and CB1-R puncta intensity is decreased in SPD tissue.
“In addition, synaptic PV and CB1-R puncta intensity was decreased in SPD tissue (Fig. 4D).”
Quote in the paperSubstantial claim - Findingown data
The density of PV-positive cells in the mPFC is not different between SPD and CTL rats.
“The density of GAD67-positive interneurons (Fig. 3B) and PV-positive cells (Fig. 3C) in the mPFC was not different between SPD and CTL rats.”
Quote in the paperSubstantial claim - Findingown data
SPD1h rats' pinning and pouncing rates were four to six times higher compared with socially housed rats of the same age.
“This is four to six times higher compared with socially housed rats of the same age, which typically show 40-60 pins per hour (Vanderschuren et al., 2008;Schneider et al., 2016b).”
Quote in the paperNot a substantial claim - Findingown data
The frequency of miniature inhibitory currents (mIPSCs) was reduced in SPD slices.
“The frequency of miniature inhibitory currents (mIPSCs) was also reduced in SPD slices (Fig. 1H), while mIPSC amplitudes (Fig. 1I) were not affected.”
Quote in the paperSubstantial claim - Findingown data
SPD rats showed an enhanced tendency to stay at a lever after it was rewarded (win-stay behavior).
“SPD rats showed an enhanced tendency to stay at a lever after it was rewarded (so-called”
Quote in the paperNot a substantial claim - Findingown data
SPD and SPD1h rats showed a tendency to remain at the previously chosen lever.
“showing a tendency to remain at the previously chosen lever.”
Quote in the paperSubstantial claim - Findingown data
SPD and SPD1h rats shifted toward behavior congruent with a simpler heuristic strategy as reversal learning progressed.
“the SPD and SPD1h rats shifted toward behavior congruent with a simpler heuristic strategy as reversal learning progressed (Fig. 8B, middle and right panel)”
Quote in the paperSubstantial claim - Findingown data
Decay kinetics of mIPSCs were unaffected in SPD slices.
“Decay kinetics (Fig. 1K) and intrinsic excitability (Fig. 2A-C) were unaffected.”
Quote in the paperNot a substantial claim - Findingown data
Even after several weeks of unrestricted social interactions, pronounced changes in PFC function and cognition were present.
“However, even after several weeks of unrestricted social interactions, pronounced changes in PFC function and cognition were present.”
Quote in the paperSubstantial claim - Findingown data
The reduction in mIPSC frequency in SPD slices was accompanied by an increase in the average rise time.
“The reduction in mIPSC frequency in SPD slices was accompanied by an increase in the average rise time (Fig. 1J), suggesting that particularly mIPSCs with fast kinetics were lost.”
Quote in the paperNot a substantial claim - Findingown data
When normalized and pooled across both batches, the number of reversals in the SPD group was clearly above CTL.
“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 - Findingown data
Somata of L5 pyramidal cells have similar size in SPD and CTL tissue.
“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 - Findingown data
The SPD group showed consistently more win-stay choices than CTL rats in all sessions.
“we observed consistently more win-stay choices in the SPD group compared with CTL rats in all sessions”
Quote in the paperSubstantial claim - Findingown data
Social play deprivation from P21 until P42 affects cognitive skills in adulthood.
“and affects cognitive skills in adulthood.”
Quote in the paperSubstantial claim - Findingown data
mIPSC amplitudes were not affected in SPD slices.
“The frequency of miniature inhibitory currents (mIPSCs) was also reduced in SPD slices (Fig. 1H), while mIPSC amplitudes (Fig. 1I) were not affected.”
Quote in the paperNot a substantial claim - Findingown data
One daily hour of play during SPD partially rescues behavioral performance in the PRL.
“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.”
Quote in the paperSubstantial claim - Findingown data
In the PRL task, SPD1h rats made more correct choices compared with CTL rats.
“as SPD1h rats made more correct choices compared with CTL rats (Fig. 7C)”
Quote in the paperNot a substantial claim - Findingown data
The density of VGAT puncta is not different in SPD and CTL tissue.
“The density of VGAT puncta was not different in SPD and CTL tissue, but the density of PV synapses (colocalizing with VGAT) was significantly lower in SPD tissue compared with CTL tissue (Fig. 4C).”
Quote in the paperSubstantial claim - Findingown data
Perisomatic inhibition onto L5 cells was reduced in the adult mPFC after SPD.
“We observed that perisomatic inhibition onto L5 cells was reduced in the adult mPFC after SPD.”
Quote in the paperSubstantial claim - Findingown data
Social play deprivation from P21 until P42 reduces specific inhibitory connections in the PFC.
“Here, we found that social play deprivation from P21 until P42 reduces specific inhibitory connections in the PFC”
Quote in the paperSubstantial claim - Findingown data
The SPD1h group did not show the increase in win-stay choices seen in the SPD group.
“but this effect was not present in the SPD1h group (Fig. 7D)”
Quote in the paperSubstantial claim - Findingown data
One daily hour of play during SPD does not prevent the decrease in PFC inhibitory synaptic inputs.
“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.”
Quote in the paperSubstantial claim - Findingown data
After normalization to CTL, SPD win-stay choices were clearly different from both other groups.
“When we normalized the win-stay responses in each group to the CTL group, SPD choices are clearly different from both other groups.”
Quote in the paperNot a substantial claim - Findingown data
Around 75% of pins and pounces occurred in the first half hour of the session.
“Quantification of the social interactions showed that around 75% of pins and pounces occurred in the first half hour of the session (Fig. 6E-F).”
Quote in the paperSubstantial claim - Findingown data
Intrinsic excitability was unaffected in SPD slices.
“Decay kinetics (Fig. 1K) and intrinsic excitability (Fig. 2A-C) were unaffected.”
Quote in the paperNot a substantial claim - Findingown data
The density of CB1-R synapses is not altered in SPD tissue.
“The density of CB1-R synapses was not altered.”
Quote in the paperNot a substantial claim - Findingown data
SPD is associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells.
“This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells.”
- Also stated in: § Results · plain
“the density of PV synapses (colocalizing with VGAT) was significantly lower in SPD tissue compared with CTL tissue (Fig. 4C).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
mIPSC amplitudes were not different between groups.
“Amplitudes of the events were not different between groups (Fig. 9C).”
Quote in the paperNot a substantial claim - Findingcitation
SPD1h rats' pinning and pouncing rates were comparable to rats in other studies that were isolated for 24 h.
“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 - Findingown data
Models containing a stickiness parameter always performed best.
“models that contained a”
Quote in the paperNot a substantial claim - Findingown data
The density of GAD67-positive interneurons in the mPFC is not different between SPD and CTL rats.
“The density of GAD67-positive interneurons (Fig. 3B) and PV-positive cells (Fig. 3C) in the mPFC was not different between SPD and CTL rats.”
Quote in the paperSubstantial claim - Findingown data
CTL rats' behavior was best described by a Q-learning model in all sessions.
“The behavior of CTL rats was best described by a Q-learning model in all sessions (Fig. 8B, left panel)”
- Also stated in: § Discussion · hedged
“CTL rats seemed to follow a sophisticated cognitive strategy which was well-described by a Q-learning model.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Findingown data
There was no difference between groups in choices after nonrewarded trials.
“There was no difference between groups in their choices after nonrewarded trials (CTL: 45 6 8% SPD: 45 6 7%; SPD1h: 45 6 7%; ANOVA p = 0.86).”
Quote in the paperNot a substantial claim - Findingown data
SPD1h rats played very intensely during the first 15-30 min of each play session.
“We observed that SPD1h rats played very intensely during the first 15-30 min of each play session”
Quote in the paperSubstantial claim - Findingown data
There is a reduced level of PV and CB1 expression in prefrontal L5 inhibitory synapses after SPD.
“In addition, we report a reduced level of PV and CB1 expression in prefrontal L5 inhibitory synapses after SPD.”
Quote in the paperSubstantial claim - Findingown data
The reduction in mIPSC frequency was associated with a comparable reduction in perisomatic PV synapses.
“associated with a comparable reduction in perisomatic PV synapses”
Quote in the paperSubstantial claim - Findingown data
The total amount of play in SPD1h rats made up a substantial fraction of the daily play that socially housed CTL rats show at this age.
“resulting in a total amount of play that makes up a substantial fraction of the daily play that socially housed CTL rats show at this age.”
Quote in the paperSubstantial claim - Findingown data
The behavior of SPD1h rats fell in between SPD and CTL rats.
“Our observation that the behavior of SPD1hr fell in between SPD and CTL rats”
Quote in the paperSubstantial claim - Interpretationreasoning
Proper PFC development may require complex cognitive and social stimuli.
“By analogy of sensory cortex development, proper PFC development may require complex cognitive and social stimuli.”
Quote in the paperSubstantial claim - Premisecitation
Social play subserves the development of PFC-dependent skills such as flexibility, creativity, and decision-making.
“In this way, social play subserves the development of PFC-dependent skills such as flexibility, creativity, and decision-making (Spinka et al., 2001;Pellis and Pellis, 2009;Vanderschuren and Trezza, 2014).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Spinka et al., 2001 source
- cites Pellis and Pellis, 2009
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Vanderschuren and Trezza, 2014
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Lesions or inactivation of the PFC impair social play.
“Social play behavior involves PFC activity (van Kerkhof et al., 2013b), and lesions or inactivation of the PFC have been found to impair social play (Bell et al., 2009;van Kerkhof et al., 2013a).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Bell et al., 2009 source
- cites van Kerkhof et al., 2013a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Social play behavior involves PFC activity.
“Social play behavior involves PFC activity (van Kerkhof et al., 2013b), and lesions or inactivation of the PFC have been found to impair social play (Bell et al., 2009;van Kerkhof et al., 2013a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites van Kerkhof et al., 2013b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation
Lack of social play experience during postweaning development causes long-lasting changes in PFC circuitry and function.
“Lack of social play experience during postweaning development has been reported to cause long-lasting changes in PFC circuitry and function (Leussis et al., 2008;Bell et al., 2010;Baarendse et al., 2013;Vanderschuren and Trezza, 2014).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
1 h daily play during SPD only partially restores cognitive performance in SPD rats.
“Furthermore, it shows that 1 h daily play during SPD only partially restores the cognitive performance in SPD rats.”
- Also stated in: § Discussion · plain
“although 1 h of daily condensed play (roughly equivalent to 4-6 h of”
- Also stated in: § Discussion · plain
“but it partially rescued behavior in adulthood.”
Quote in the paperSubstantial claim- Rests on an assumption: 1 h of daily condensed play is roughly equivalent to 4-6 h of normal play.
- Also stated in: § Discussion · plain
- Interpretationreasoning
These alterations have important consequences for cognitive flexibility.
“with important consequences for cognitive flexibility.”
Quote in the paperSubstantial claim - Interpretationown data
Adult SPD rats use a more simplified cognitive strategy than controls in the PRL task.
“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.”
Quote in the paperSubstantial claim- The authors state this as an assumption: The random choice model's assumption that animals choose randomly is valid for the computational modeling.
- The authors state this as an assumption: Choice behavior in the computational models follows a Softmax function.
- The authors state this as an assumption: Lever values are updated according to a Q learning rule.
- Interpretationown data
The organization of the adult GABAergic system in the mPFC of rats is robustly altered when rats are deprived of social play behavior during development.
“Our findings demonstrate that the organization of the adult GABAergic system in the mPFC of rats is robustly altered when rats are deprived of social play behavior during development”
Quote in the paperSubstantial claim - Interpretationown data
Juvenile SPD alters PFC function and cognitive flexibility in adulthood.
“These data indicate that juvenile SPD alters PFC function and cognitive flexibility in adulthood.”
Quote in the paperSubstantial claim - Interpretationreasoning
Particularly mIPSCs with fast kinetics were lost in SPD slices.
“The reduction in mIPSC frequency in SPD slices was accompanied by an increase in the average rise time (Fig. 1J), suggesting that particularly mIPSCs with fast kinetics were lost.”
Quote in the paperNot a substantial claim - Interpretationown data
The lack of statistical significance in the second batch was probably because of a ceiling effect due to higher overall performance of all rats compared with the previous PRL experiment.
“This was probably because of a ceiling effect because of the higher overall performance of all rats compared with the previous PRL experiment (see Materials and Methods and compare values in Figs.7B and 5D).”
Quote in the paperNot a substantial claim - Interpretationreasoning
Integrated neuronal activity likely drives PFC maturation during development.
“This integrated neuronal activity likely drives PFC maturation during development”
Quote in the paperSubstantial claim - Interpretationreasoning
A reduction in mIPSCs with fast rise times suggests that inhibitory synapses at perisomatic locations were affected.
“A reduction in mIPSCs with fast rise times suggests that inhibitory synapses at perisomatic locations were affected.”
Quote in the paperSubstantial claim - Premisecitation
The postweaning time window is a critical period for PFC maturation and behavioral development.
“consistent with earlier studies that identified this time window as a critical period for PFC maturation and behavioral development”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
The social play deprivation period P21-42 is the period in life when social play is most abundant.
“Rats were deprived of social play for a period of three weeks postweaning (P21-P42), which is the period in life when social play is most abundant (Baenninger, 1967;Meaney and Stewart, 1981;Panksepp, 1981).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Social play enhances neuronal activity in a broad network of limbic and corticostriatal structures.
“Social play enhances neuronal activity in a broad network of limbic and corticostriatal structures”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Gordon et al., 2002 source
- cites van Kerkhof et al., 2013b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data
Cognitive performance in adult rats was altered after SPD.
“These observations indicate that cognitive performance in adult rats was altered after SPD.”
Quote in the paperSubstantial claim - Interpretationown data
The amount of play in SPD1h rats was not enough to prevent the reduction in prefrontal inhibition after SPD.
“As this was not enough to prevent the reduction in prefrontal inhibition after SPD”
Quote in the paperSubstantial claim - Interpretationown data
Unrestricted, voluntarily elicited or repeated play is necessary for proper PFC maturation.
“it suggests the necessity of unrestricted, voluntarily elicited or repeated play for proper PFC maturation.”
Quote in the paperSubstantial claim - Interpretationcitation
The mPFC may be less involved in PRL performance in SPD rats compared with CTL rats.
“suggesting that the mPFC may be less involved in PRL performance in SPD rats compared with CTL rats.”
Quote in the paperNot a substantial claim - Interpretationreasoning
The partial rescue of behavior involves compensatory changes other than L5 inhibition.
“suggests that the partial rescue of behavior involves compensatory changes other than L5 inhibition”
Quote in the paperNot a substantial 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.
PremisecitationHow 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).
PremisecitationSensory 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).
PremisecitationSensory 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 checkedClassified as probably not a substantial claim. May combine two claims.
PremisecitationPerisomatic 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.
PremisecitationThe 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 checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA 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 checkedClassified as probably not a substantial claim.
PremisecitationA 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).
PremisecitationAlterations 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 checkedClassified as probably not a substantial claim.
PremisecitationChanges 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.
PremisecitationA 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.
InterpretationcitationReduced 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 checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationPRL 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).
PremisecitationPrevious 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).
PremisecitationPlay 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 dataRats 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 claimMay combine two claims.
Findingown dataSPD1h 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataIn 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataWhen 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 claimThe quote only partly states this claim.
Findingown dataThe 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- Also stated in: § Discussion · plain
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataPuncta 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 claimMay combine two claims.
Findingown dataThe 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 claimMay combine two claims.
Findingown dataSPD1h 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 claimMay combine two claims.
Findingown dataRats 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 claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataIn 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataSynaptic 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataSynaptic 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 claimClassified as probably not a substantial claim.
PremisecitationThe 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 checkedClassified as probably not a substantial claim.
PremisecitationThe 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 checkedMay combine two claims.
Interpretationown dataSPD 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- Also stated in: § Discussion · plain
Classified as probably not a substantial claim.
PremisecitationL5 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.
PremisecitationBehavioral 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 checkedMay combine two claims.
Interpretationown dataDaily 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- Also stated in: § Results · plain
Classified as probably not a substantial claim.
Study design and conductnone givenWe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenDetected currents were manually inspected to exclude false events.
“The detected currents were manually inspected to exclude false events.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenSeries 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 claimMay combine two claims.
Study design and conductown dataIn 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPinning 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 dataSPD 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 claimMay combine two claims.
Interpretationown dataUnrestricted 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 claimMay combine two claims.
Interpretationown dataSocial 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 claimMay combine two claims.
Interpretationown dataJuvenile 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 claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
InterpretationreasoningThe 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
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”
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
MinorThe 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.
“After the SPD period, the wall was removed and pair-wise social housing was maintained until adulthood when experiments were performed (postnatal week 8-10).”
“For slice preparation, rats (12-15 weeks of age) were anesthetized by intraperitoneal injection of sodium pentobarbital (batch 1) or induction with isoflurane (batch 2)”
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Play fighting and the development of the social brain: The rat’s tale
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Self-citationAnimal play and evolution: Seven timely research issues about enigmatic phenomena
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“Early life experience is thus highly important in shaping cognitive abilities later in life (Bijlsma et al., 2022; Jones et al., 1996).”
Self-citationGains and Losses: Resilience to Social Defeat Stress in Adolescent Female Mice
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Early life stress and altered social behaviors: A perspective across species
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Social play behavior shapes the development of prefrontal inhibition in a region-specific manner
Bijlsma, A., Vanderschuren, L. J. M. J., & Wierenga, C. J. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad212 · Cited by 16 · see citing works
“Statistical range: * p≤0.05; ** p<0.01; *** p<0.001 We previously showed that SPD during P21-42 results in a reduction of inhibitory synapses onto L5 pyramidal somata in the mPFC of adult rats (Bijlsma et al., 2022).”
BackgroundResultInfluentialSelf-citationAmygdala circuit transitions supporting developmentally-appropriate social behavior
Ferrara, N. C., & Opendak, M. M. (2023) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2023.107762 · Cited by 17 · see citing works
Play partner preferences among groups of unfamiliar juvenile male rats
Ham, J. R., & Pellis, S. M. (2024) · Scientific Reports · doi:10.1038/s41598-024-66988-w · Cited by 13 · see citing works
Santos‐Silva, T., Ülgen, D. H., Lopes, C. F. B., Guimarães, F. S., Alberici, L. C., Sandi, C., & Gomes, F. V. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02648-3 · Cited by 12 · see citing works
Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia
Achterberg, E. J. M., Biemans, B., & Vanderschuren, L. J. M. J. (2025) · Psychopharmacology · doi:10.1007/s00213-024-06559-z · Cited by 9 · see citing works
“…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…”
Self-citationNyberg, H., Bogen, I. L., Nygaard, E., Achterberg, E. J. M., & Andersen, J. M. (2024) · Psychopharmacology · doi:10.1007/s00213-024-06718-2 · Cited by 11 · see citing works
“Importantly, disrupted play experiences in young rats result in social and cognitive impairments, as well as long-lasting cellular and synaptic changes in prefrontal cortical neurons (Bijlsma et al. 2022; Baarendse et al. 2013).”
Bijlsma, A., Birza, E. E., Pimentel, T. C., Maranus, J. P. M., van Gaans, M. J. J. M., Klooster, J. G. L. T., Baars, A. M., Achterberg, E. J. M., Lesscher, H. M. B., Wierenga, C. J., et al. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16313 · Cited by 10 · see citing works
Self-citationNeurobehavioral Characterization of Perinatal Oxycodone-Exposed Offspring in Early Adolescence
Flores, A., Nguyen, N. M., Devanaboyina, M., Sanketh, S., Athota, P., Sankarasubramanian, J., Guda, C., Yelamanchili, S. V., & Pendyala, G. (2024) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-024-10129-7 · Cited by 8 · see citing works
“Impairments to social behavior are consistent with PFC deficits in several models (Sun et al. 2017; Bijlsma et al. 2022).”
Shaping the development of complex social behavior
Curley, J. P., & Champagne, F. A. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15076 · Cited by 7 · see citing works
“…of these play-induced changes to the mPFC may be limited to the juvenile period, whereas the impact of play on dendritic arbors in the orbitofrontal cortex may be maintained over the lifespan and thus responsivetoongoingchangesinthesocialenvironment, 168,169,171–173 though this may vary by species.”
BackgroundChen, X., Kim, Y., & Kawaguchi, D. (2025) · Frontiers in Neural Circuits · doi:10.3389/fncir.2025.1568610 · Cited by 9 · see citing works
Whitten, C. J., Kelly, J. R., Gillespie, A. L., Brooks, H. J. B., Hooker, M. K., Temple, A., Hennon, L. M., Kilgore, B. J., Singamaneni, Y. B., Schulz, K. M., et al. (2025) · Developmental Psychobiology · doi:10.1002/dev.70020 · Cited by 7 · see citing works
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Juvenile male rats form preferences based on strain when playing in groups but not in pairs
Ham, J. R., Jaiswal, D., Waner-Mariquito, R., Pellis, S. M., & Achterberg, E. J. M. (2025) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2025.1617178 · Cited by 5 · see citing works
Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat
Spoelder, M., Bright, Y., Morrison, M. C., van Kempen, V., de Groodt, L., Begalli, M., Schuijt, N., Kruiger, E., Bulthuis, R., Gross, G., et al. (2023) · Cells · doi:10.3390/cells12202463 · Cited by 3 · see citing works
“Moreover, a reduced dopamine modulation of prefrontal cortex function due to social isolation has been observed in several investigations [51], as well as reductions in inhibitory synapses in the PFC [52,53].”
BackgroundSelf-citationImpairment of the GABAergic system in the anterior insular cortex of heroin-addicted males
Gos, A., Steiner, J. H., Trübner, K., Mawrin, C., Kaliszan, M., & Gos, T. (2024) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-024-01848-2 · Cited by 4 · see citing works
Achterberg, E. J. M., Klooster, J. G. L. T., Pimentel, T. C., Aleksić, A., Hendriks, J., Nijhof, S. L., van der Ent, C. K., & Lesscher, H. M. B. (2024) · Frontiers in Ethology · doi:10.3389/fetho.2024.1458136 · Cited by 2 · see citing works
Escribano-Cadena, Y., Tendilla‐Beltrán, H., & Flores, G. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.07.041 · Cited by 2 · see citing works
“These connections make the PFC essential for higher-level cognitive processes, including social behavior, decision-making, motivation, and recognition-related functions (Anastasiades and Carter, 2021).”
Wallis, A. S. J., Mendl, M., Lecorps, B., & Held, S. D. E. (2025) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2025.1962 · Cited by 3 · see citing works
“However, some studies have addressed this by providing the isolated group with a short daily period of play [91] (see §2a(ii)).”
InfluentialNeurodevelopmental effects of early life stress: PFC and cognition
Rachmany, L., de Abreu, F. F., Walker, V., O'Neill, O. S., Sargin, D., & Teixeira, C. M. (2026) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2026.106663 · Cited by 4 · see citing works
The ontogeny of play in a highly cooperative monkey, the common marmoset
Godard, A. M., Burkart, J. M., & Brügger, R. K. (2025) · Animal Behaviour · doi:10.1101/2024.05.28.595935 · Cited by 2 · see citing works
Disentangling developmental effects of play aspects in rat rough-and-tumble play
Liu, Q., Радченко, М., & Špinka, M. (2024) · Biology Letters · doi:10.1098/rsbl.2024.0037 · Cited by 1 · see citing works
“This could have systemically affected their cognitive development as the 1 h play opportunity can only partially compensate for the lack of home cage play [60–62].”
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Impairment of the GABAergic system in the anterior midcingulate cortex of heroin-addicted males
von Gilsa, A., Steiner, J. H., Gos, A., Trübner, K., Mawrin, C., Kaliszan, M., Nickl-Jockschat, T., & Gos, T. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-01992-3 · Cited by 2 · see citing works
“However, at the synaptic level, this activity is more accurately represented by neuropil than by somata density [32, 33].”
Ham, J. R., Iwaniuk, A. N., & Pellis, S. M. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116198 · Cited by 1 · see citing works
Disruption of social play influences development of caution in juvenile ground squirrels
Ryan, W. J., Kuan, M. B., & Nunes, S. (2024) · Frontiers in Ethology · doi:10.3389/fetho.2024.1410334 · Cited by 2 · see citing works
The role of the dopamine D1 receptor in anticipatory pleasure and social play
Witt, K. M., Harper, D. N., & Ellenbroek, B. A. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110225 · Cited by 1 · see citing works
Treatment with furosemide indirectly increases inhibitory transmission in the developing hippocampusPreprint
Peerboom, C., Wijne, T., & Wierenga, C. J. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.11.548438 · Cited by 1 · see citing works
Self-citationUnravelling the Role of the Dopamine D1 Receptor in Anhedonia, Asociality, and Avolition
Witt, K. (2023) · doi:10.26686/wgtn.24646128 · Cited by 1 · see citing works
Rat Anterior Insula Symmetrically Represents Tickling-Induced Playful EmotionsPreprint
Dagher, S., & Ishiyama, S. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.02.587725 · Cited by 1 · see citing works
How social play experience shapes development of higher brain function
Bijlsma, A. (2023) · doi:10.33540/1927
Self-citationSantos‐Silva, T. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2023.tde-10112023-160657
Alexander, J. P., & Mooney, S. M. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114695
Shonka, S., & Hylin, M. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.24.655898 · Cited by 1 · see citing works
Evaluation of the Effects of Enlarged Housing on Social Play and Reward Seeking in Rats
Achterberg, E. J. M., Baars, A. M., van Hal, D. A., Lesscher, H. M. B., & Loo, P. L. P. V. (2025) · Animals · doi:10.3390/ani15182757
The role of endocannabinoids in nonpharmacological addiction
Mostallino, R., & Fattore, L. (2025) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-443-13908-6.00025-6
Impairment of the GABAergic system in the prefrontal cortex of male heroin addicts
von Gilsa, A., Steiner, J. H., Gos, A., Trübner, K., Mawrin, C., Kaliszan, M., Nickl-Jockschat, T., & Gos, T. (2025) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-025-02139-0 · Cited by 1 · see citing works
“However, at the synaptic level, this activity is more accurately represented by neuropil than by somata density [ 30 , 31].”
Taylor, A. J., Carrasco-Gutiérrez, R., Olea-Araya, A., Moya, P. R., & Dagnino‐Subiabre, A. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5770906
Heightened Play following Play Observation in the Absence of 22KHz Calls in Juvenile RatsPreprint
Michon, F., Achterberg, E. J. M., Kaufmann, L. V., Packheiser, J., Bos, S., van Reenen, K., Gazzola, V., & Keysers, C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.31.697143
Methylation and merriment: an exploration of epigenetic mechanisms underlying play behaviour
Malka, R. J., Arranz, M., & Baselga-Carretero, I. (2026) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1002/brv.70142
“Juvenile rats deprived of social play used simpler strategies for complex tasks when adult, with fewer mPFC inhibitory synapses (Bijlsma et al ., 2022).”
Neural Mechanisms of Social Homeostasis: Dynamic Range Plasticity
Cressy, J., Jia, C., Salk, J. D., & Tye, K. M. (2026) · Journal of Neuroscience · doi:10.1523/jneurosci.0224-25.2025
“Developmentally, early social experience (i.e., social play) is required for maturation of parvalbumin-interneuron inhibition in mPFC, establishing excitatory inhibitory (E/I) balance that stabilizes predictive control (Bijlsma et al., 2022).”
The role of sensory experience in the maturation of prefrontal cortical circuits
Anqueira-González, A., & Canetta, S. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1808558
“Extending isolation slightly later from PN28-PN63 (juvenile to early adulthood) further compromises parvalbumin interneuron number and activity, as well as cognitive flexibility (Bijlsma et al., 2022; Li et al., 2022).”
The spectre and promise of species diversity
Pellis, S. M. (2026) · International Journal of Play · doi:10.1080/21594937.2026.2650984
“…2016; VanRyzin et al., 2020), and, indeed, the most empirically well-supported demonstrations of the functional benefits associated with play, linking improved behavioral outcomes with underlying neuronal changes have been with rats (Bijlsma et al., 2022; Ham et al., 2024; Pellis et al., 2023).”
Heightened play following play observation in the absence of 22-kHz calls in juvenile rats
Michon, F., Achterberg, E. J. M., Kaufmann, L. V., Packheiser, J., Bos, S., van Reenen, K., Gazzola, V., & Keysers, C. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116382 · Cited by 1 · see citing works
Early life adversity disrupts adult social reward motivationPreprint
Stricklin, M. C., Nyakoa, J. E., Mesape, K. M., Bhat, M. S., Rolle, S. S., Bangasser, D. A., & Cuarenta, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.21.739864
“In rodents, social interactions such as juvenile play behavior represent a highly conserved and developmentally sensitive form of social engagement that emerges early and is essential for the maturation of social and affect-related processes and cognitive functions 17,19,20 .”
- 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)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2022-10-17
- Volume
- 42
- Issue
- 46
- Pages
- 8716-8728
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC9671579
- 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
- hybrid
- doi.org
- Licence
- 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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