Brain Structure and Function

, Volume 219, Issue 4, pp 1181–1211 | Cite as

Cellular activation in limbic brain systems during social play behaviour in rats

  • Linda W. M. van Kerkhof
  • Viviana Trezza
  • Tessa Mulder
  • Ping Gao
  • Pieter Voorn
  • Louk J. M. J. Vanderschuren
Original Article


Positive social interactions during the juvenile and adolescent phases of life are essential for proper social and cognitive development in mammals, including humans. During this developmental period, there is a marked increase in peer–peer interactions, signified by the abundance of social play behaviour. Despite its importance for behavioural development, our knowledge of the neural underpinnings of social play behaviour is limited. Therefore, the purpose of this study was to map the neural circuits involved in social play behaviour in rats. This was achieved by examining cellular activity after social play using the immediate early gene c-Fos as a marker. After a session of social play behaviour, pronounced increases in c-Fos expression were observed in the medial prefrontal cortex, medial and ventral orbitofrontal cortex, dorsal striatum, nucleus accumbens core and shell, lateral amygdala, several thalamic nuclei, dorsal raphe and the pedunculopontine tegmental nucleus. Importantly, the cellular activity patterns after social play were topographically organized in this network, as indicated by play-specific correlations in c-Fos activity between regions with known direct connections. These correlations suggest involvement in social play behaviour of the projections from the medial prefrontal cortex to the striatum, and of amygdala and monoaminergic inputs to frontal cortex and striatum. The analyses presented here outline a topographically organized neural network implicated in processes such as reward, motivation and cognitive control over behaviour, which mediates social play behaviour in rats.


Social behaviour Adolescence c-Fos Prefrontal cortex Striatum Amygdala Thalamus Mesencephalon 



Anterior cingulate cortex


Agranular insular cortex dorsal part


Agranular insular cortex ventral part


Basolateral amygdala


Bed nucleus of the stria terminalis


Central amygdala


Central medial thalamic nucleus


Central lateral thalamic nucleus


Dorsolateral orbitofrontal cortex


Dorsal raphe nucleus anterior level


Dorsal raphe nucleus posterior level


Dorsal striatum


Infralimbic cortex


Intermediodorsal thalamic nucleus lateral part


Intermediodorsal thalamic nucleus medial part


Lateral amygdala


Lateral globus pallidus


Locus coeruleus


Lateral nucleus accumbens core


Laterodorsal tegmental nucleus


Lateral orbitofrontal cortex


Lateral nucleus accumbens shell


Medial nucleus accumbens core


Mediodorsal thalamic nucleus


Medial amygdala


Medial orbitofrontal cortex


Medial prefrontal cortex


Medial nucleus accumbens shell


Nucleus accumbens core


Nucleus accumbens shell


Orbitofrontal cortex


Olfactory tubercle


Paracentral thalamic nucleus


Pedunculopontine tegmental nucleus


Prelimbic cortex


Prelimbic cortex dorsal part


Prelimbic cortex ventral part


Paraventricular thalamic nucleus lateral part


Paraventricular thalamic nucleus medial part


Rostromedial tegmental nucleus


Substantia nigra pars compacta


Substantia nigra pars reticulata


Striatal region receiving input from the cortical region mentioned with it


Ventrolateral orbitofrontal cortex


Ventral orbitofrontal cortex


Ventral pallidum


Ventral striatum


Ventral nucleus accumbens shell


Ventral tegmental area



This study was supported by National Institute on Drug Abuse Grant R01 DA022628 (L.J.M.J.V.), Netherlands Organization for Scientific Research (NWO) Veni grant 91611052 (V.T.) and Marie Curie Career Reintegration Grant PCIG09-GA-2011-293589 (V.T.).


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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Linda W. M. van Kerkhof
    • 1
  • Viviana Trezza
    • 1
    • 2
  • Tessa Mulder
    • 1
  • Ping Gao
    • 3
  • Pieter Voorn
    • 3
  • Louk J. M. J. Vanderschuren
    • 1
    • 4
  1. 1.Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of NeuroscienceUniversity Medical Center UtrechtUtrechtThe Netherlands
  2. 2.Department of BiologyUniversity “Roma Tre”RomeItaly
  3. 3.Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam VU University Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary MedicineUtrecht UniversityUtrechtThe Netherlands

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