PNNficity

Neurodevelopmental disorders include conditions such as autism spectrum disorders (ASD), for which effective treatments are lacking. Neurofibromatosis type 1 (NF1) is a syndromic model of ASD exhibiting excitation/inhibition (E/I) imbalance. Although Nf1+/- mice display dysregulated parvalbumin-positive (PV) neuron excitability and neural plasticity, leading to memory and social behavior abnormalities, the underlying mechanisms are not understood. Perineuronal nets (PNNs) are extracellular structures that regulate PV maturation and neural plasticity. Here, we posit that PNNs play a key role in the neurocircuitry alterations of NF1, and its manipulation may offer a novel means to ameliorate cognitive and behavioral deficits. Using different molecular, imaging, and electrophysiology techniques, we will characterize PNNs in an Nf1+/- mouse model while applying in vivo paradigms of visual cortical plasticity or a socially challenging protocol. We will also test the potential of PNN modulation as an approach to rescue plasticity and behavioral phenotype in Nf1+/- mice.

neurofibromatosis type 1 | autism spectrum disorder | neural plasticity | perineuronal nets | parvalbumin neurons

2024-2027