Study of the role of perineuronal nets in adult brain plasticity in rodents

Brain plasticity also known as “neural plasticity” is the capacity of the nervous system to modify itself, functionally and structurally, in response to experience and injury; it therefore play a key role in learning, memory and behaviour. Some of its features regard NMDA receptor in synaptic transmission, and perineuronal nets (PNNs). A well-known example of plasticity at the cellular level is long-term potentiation (LTP) and some of its major players are N-methyl-D-aspartate receptors (NMDARs). Many other factors are involved directly or undirectly in brain plasticity, and recently perineuronal nets (PNNs) have emerged as important plasticity regulators. PNNs are a specialized form of extracellular matrix surrounding many neurons in the central nervous system (CNS), involved in the control of plasticity in the adult, and in the closure of the “critical periods” of plasticity during brain development. Moreover PNNs exert multiple functions, including the structural stabilization of synapses synapses, and the prtotection of neurons from oxidative stress and neurotoxins. Indeed, removal of PNNs can render neurons vulnerable to damage. PNNs are also involved in cognition and seem to be crucial for the maintenance and the updating of memories. Common pathophysiological features of different neuro-diseases, including Autism spectrum disorders (ASD), are consistent with a removal of “brakes” on plasticity, such as altered excitatory/inhibitory balance, myelin deficits or perineuronal nets (PNNs) loss. For PNN maintenance in the adult brain, the regular expression of NMDAR on the cell membrane seems to be essential. Accordingly NMDAR and PNN alterations characterizes many cognitive disorders and neuropathologies. The preliminary results illustrated by this thesis work demonstrate the involvement of PNNs in a new rat model of ASD and the close relationship existing between NMDAR activity and PNNs in adult brain plasticity and in learning and memory functions.