Perineuronal nets in memory processing and behavior

Abstract

This doctoral thesis entails work on learning and memory with the goal of understanding mechanisms that regulate plasticity and affect memory processing. Learning paradigms described here involve classical Pavlovian conditioning using an aversive stimulus to create visual fear memories. Central to the work is the use of visual stimuli and understanding how visual cues paired with a salient stimulus cause formation of memories in rodents. Visual cues guides goal directed behavior and helps us recognize dangers, nevertheless, auditory cues are most commonly used when doing associative learning in rodents. In paper I, we used a standard fear conditioning paradigm in an operant chamber. While in paper III, we describe a method of doing visual fear conditioning with head-fixed mice, including how to monitor learning through studying behavior responses. In paper I and II we focus on the perineuronal nets (PNNs), a specialized form of extracellular matrix, and how they reduce plasticity in the adult brain. We also study the neurons PNNs most frequently surround, namely the inhibitory neuron expressing parvalbumin (PV+ interneuron). This neuron subtype, like the PNNs, is important for directing maturation of brain functions in the transition from juvenile to adult. Adult brains are less plastic, less amenable than developing brains. This reduction in plasticity is partly caused by the formation of PNNs. The PNNs form a rigid netting structure around neurons, creating a barrier against alterations. The cerebral cortex is teeming with PNNs, they assemble at the end of critical periods, times of heightened plasticity in the sensory cortices.