Endogenous regulation of perineuronal nets and their role in learning and spatial information transfer between the entorhinal cortex and hippocampus (copy)

The healthy brain operates through a complex balance between excitation and inhibition. In order to reveal the operating principles of the brain it is critical to understand how different cell classes contribute to cortical processing and plasticity. In the proposed experiments we will remove the perineuronal nets which are proteoglycans embodying specific neuron populations in the brain, and block endogenously produced matrix degrading proteins called matrix metalloproteases (MMPs). The PNNs are suggested to play a pivotal role in stabilizing synapses and control the onset and closure of periods of heightened plasticity in the cortex. We will degrade these PNN in different brain areas to reveal their function for normal cortical function and specifically during activity-dependent plasticity and in memory processing. In addition we will also block MMPs in order to limit the natural remodeling of PNNs after a learning task. The goal of this research is to understand the neural mechanisms of how sensory experiences are transformed into long-lasting memories in the brain.