The Role of Perineuronal Nets in Regulating Barrel Cortex Physiology

The ability of the brain to adapt to changing environmental conditions is regulated by genetic and environmental factors. One component of the brain extracellular matrix, a scaffold of proteins and proteoglycans, tightly ensheaths the soma and proximal processes of neurons. These Perineuronal nets (PNNs) play protective and structural roles in the brain, but also regulate plasticity and behavior. Their developmental expression is highly attenuated following sensory deprivation, or pharmacological silencing of neuronal activity. Thus, PNNs contribute to the activity dependent regulation of plasticity in the brain. Although PNNs are relatively ubiquitous in the neocortex, little is known about the degree to which they impact the physiology of the diverse neuronal phenotypes that exist there. This research focused on determining the experience dependent maturation of PNNs in different cortical layers and whether the alterations to neuronal intrinsic properties following sensory deprivation could be explained by PNN reductions. Finally, we sought to determine what aspects of intrinsic and synaptic physiology are regulated by PNNs in the hope of providing future direction for understanding their fundamental role in the neocortex. This research produced a number of key findings: 1) PNN development in the granular and supragranular layers depend more on sensory input than the infragranular layers ; 2) sensory deprivation induces reductions in spike frequency, probability and mildly reduces input resistance, while significantly increasing action potential amplitude in fast spiking (FS) inhibitory interneurons; 3) enzymatic digestion of PNNs only mildly impac spike frequency and firing probability, but significantly reduces input resistance, and spike amplitude in FS inhibitory interneurons and 4) Perturbation of PNNs reduces the temporal range of spontaneous EPSPs onto FS cells and reduces the spontaneous EPSP frequency onto low threshold spiking putative interneurons. Other minor alterations to putative excitatory intrinsic properties were also detected. The similarity in features that are modulated by both sensory deprivation and perturbation of PNNs suggests that the presence of PNN may only serve as a partial mechanism for experience dependent regulation of physiology. Nevertheless, PNN perturbation impacts important features of intrinsic physiology that can affect inhibitory interneuron networks. These data are relevant to understanding the mechanisms of brain reorganization and plasticity and suggest that the gradual stabilization of brain extracellular matrix across development plays a role in stabilizing neuronal networks and their cognitive/behavioral outputs