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Developmental CA2 perineuronal net reduction restores social memory in Shank3 mutant mice
Emma J Diethorn1, Aarushi B Rathaur1, Brayan R Ruiz Lopez1
1Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.
Communications Biology
|June 5, 2026
Summary
Shank3B knockout mice show developmental social recognition deficits linked to CA2 network issues. Early intervention by reducing perineuronal nets (PNNs) can restore social recognition in these autism spectrum disorder models.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Autism Spectrum Disorder (ASD) and Phelan-McDermid syndrome (PMDS) are associated with social recognition deficits.
- Shank3B knockout (KO) mice model these conditions but lack developmental insights into their social deficits.
Purpose of the Study:
- Investigate the developmental mechanisms of social recognition deficits in Shank3B KO mice.
- Examine the role of CA2 network and perineuronal nets (PNNs) in early social interaction.
Main Methods:
- Utilized Shank3B KO mice as a genetic model for ASD and PMDS.
- Analyzed CA2 network activity, perineuronal nets (PNNs), and semaphorin-3A levels during development.
- Assessed social recognition behavior in developing and adult mice.
Main Results:
- Shank3B KO mice exhibited persistent short-term social recognition deficits from development into adulthood.
- Excessive PNNs in the developing CA2 region sequestered semaphorin-3A, leading to afferent overgrowth.
- Reducing PNN levels reversed these deficits, restoring semaphorin-3A, afferent input, and social recognition.
Conclusions:
- Excessive PNN formation in the developing CA2 network impairs social recognition by disrupting afferent input.
- Early life intervention targeting PNNs can normalize social recognition and CA2 network activity.
- Findings suggest PNNs as a potential therapeutic target for social deficits in neurodevelopmental disorders.
