Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2 Pyramidal Neurons

• Published in: The Journal of neuroscience 2016-06, Vol.36 (23), p.6312-6320
• Main Authors: Carstens, Kelly E, Phillips, Mary L, Pozzo-Miller, Lucas, Weinberg, Richard J, Dudek, Serena M
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; CA2 Region, Hippocampal - cytology; Excitatory Amino Acid Agents - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Extracellular Matrix - metabolism; Extracellular Matrix Proteins - metabolism; Female; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - physiology; Glutamate Decarboxylase - genetics; Glutamate Decarboxylase - metabolism; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net - drug effects; Nerve Net - physiology; Nerve Net - ultrastructure; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Pyramidal Cells - ultrastructure; Satellite Cells, Perineuronal - drug effects; Satellite Cells, Perineuronal - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.0245-16.2016

Long-term potentiation of excitatory synapses on pyramidal neurons in the stratum radiatum rarely occurs in hippocampal area CA2. Here, we present evidence that perineuronal nets (PNNs), a specialized extracellular matrix typically localized around inhibitory neurons, also surround mouse CA2 pyramidal neurons and envelop their excitatory synapses. CA2 pyramidal neurons express mRNA transcripts for the major PNN component aggrecan, identifying these neurons as a novel source for PNNs in the hippocampus. We also found that disruption of PNNs allows synaptic potentiation of normally plasticity-resistant excitatory CA2 synapses; thus, PNNs play a role in restricting synaptic plasticity in area CA2. Finally, we found that postnatal development of PNNs on CA2 pyramidal neurons is modified by early-life enrichment, suggesting that the development of circuits containing CA2 excitatory synapses are sensitive to manipulations of the rearing environment. Perineuronal nets (PNNs) are thought to play a major role in restricting synaptic plasticity during postnatal development, and are altered in several models of neurodevelopmental disorders, such as schizophrenia and Rett syndrome. Although PNNs have been predominantly studied in association with inhibitory neurons throughout the brain, we describe a dense expression of PNNs around excitatory pyramidal neurons in hippocampal area CA2. We also provide insight into a previously unrecognized role for PNNs in restricting plasticity at excitatory synapses and raise the possibility of an early critical period of hippocampal plasticity that may ultimately reveal a key mechanism underlying learning and memory impairments of PNN-associated neurodevelopmental disorders.