Analysis of perineuronal net expression in brain areas controlling cognitive functions in laboratory rodent models

Perineuronal nets (PNNs) are lattice-like aggregates of extracellular matrix (ECM) molecules that enwrap the soma and dendrites of some type of neurons in the central nervous system (CNS). Although PNNs have been discovered a century ago now, their function is not yet fully understood. The past 10 years have seen the gradual recognition that the PNNs play a remarkable role in controlling synaptic plasticity. It has been demonstrated that their formation coincides with the end of critical periods, important windows of enhanced synaptic plasticity during brain development. In the adult brain, on the other hand, PNNs seem to be crucial in the regulation of cognitive processes, however, the mechanisms involved are still largely unknown, limiting the knowledge about their mechanisms of function especially in the mature nervous system. PNNs are form of plasticity that are activity-dependent and therefore highly dependent on the homeostasis between excitation and inhibition (E/I). For this reason, N-methyl-D-aspartate receptors (NMDARs) are also thought to play an essential role in the formation and maintenance of PNNs, and they may cooperate in regulating learning and memory functions. In agreement, their role has been implicated in memory formation and consolidation, opening new possibilities for therapeutic approaches to treat fear and anxiety-related disorders. Alterations in PNNs have been found in different types of disease characterized by deficits in E/I balance, including autism spectrum disorder (ASD), where a disequilibrium between triggers and brakes of molecular plasticity during critical periods may be the cause of developmental delay, increased anxiety and decreased expression of social and cognitive functions. Considering their demonstrated role in psychiatric and neurodevelopmental disorders, it is important to better understand the interaction between PNNs and the CNS cells in shaping plasticity in both the developing and mature brain. Because of this close relationship, nowadays the term ‘tetrapartite’ synapse refers to a synapse that comprise not only the pre- and postsynaptic neuron, but also glial cells and the ECM, that actively participate into it. The present study aims to better comprehend the role of PNNs in the adult brain. To do so, their expression was analysed in two different animal models: ASD-like rat, offspring of social isolated (SI) parents; and a mouse model where NMDARs have been deleted by using rAAV in both amygdala and prefrontal cortex (PFC).