Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats
- Ate Bijlsma1,2,*,
- Azar Omrani1,3,*,
- Marcia Spoelder2,*,
- Jeroen P.H. Verharen2,3,
- Lisa Bauer1,
- Cosette Cornelis2,
- Beleke de Zwart2,
- René van Dorland1,
- Louk J.M.J. Vanderschuren2, and
- Corette J. Wierenga1
- 1Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands
- 2Department of Population Health Sciences, Section Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, 3584 CM, Utrecht, The Netherlands
- 3Department of Translational Neuroscience, University Medical Center Utrecht, 3584 CG, Utrecht, The Netherlands
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Author contributions: A.B., A.O., L.J.M.J.V., and C.J.W. designed research; A.B., A.O., M.S., L.B., C.C., and B.d.Z. performed research; A.B., A.O., M.S., J.P.H.V., L.B., C.C., B.d.Z., and R.v.D. analyzed data; A.B. wrote the first draft of the paper; A.B., L.J.M.J.V., and C.J.W. edited the paper; L.J.M.J.V. and C.J.W. wrote the paper.
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↵*A.B., A.O., and M.S. contributed equally to this work.
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.
- brain development
- cognitive performance
- experience-dependent plasticity
- prefrontal cortex
- social play
- synaptic currents
- Received March 11, 2022.
- Revision received August 12, 2022.
- Accepted September 20, 2022.
- Copyright © 2022 the authors
