Abstract Sensory Deprivation profoundly impacts cortical circuits which in turn impact organismal functioning from mouse to man. Traditionally research has focused on how neurons respond to changes in sensory experience during development. Recently attention has been drawn to non- neuronal elements such as microglia and the perineuronal net (neuron specific form of the extracellular matrix). Microglia, the brains immune cells, alter their morphology in response to whisker trimming evoked sensory deprivation, their somata enlarge and their process retract, hallmarks of their activated state. Coincident with this, the perineuronal net is reduced preferentially around parvalbumin positive GABAergic interneurons. Physiological studies have shown that these neurons play a key role in regulating cortical excitability and following perineuronal net digestion we found their intrinsic physiological properties become altered (lower probability of spiking, lower input resistance). Our overarching hypothesis is that sensory deprivation activates microglia which in turn shape the perineuronal net. We will investigate this causal relationship by depleting microglia while trimming the animal’s whiskers and evaluating the perineuronal net. The functional consequences of this relationship will be studied using whole-cell patch clamp recordings in the thalamocortical slice and finally the behavioral ramifications will be assayed using a texture based novel object paradigm.

Public Health Narrative Proper microglia functioning is necessary for a healthy brain; disruption of microglia can alter behavior and lead to neurological pathologies. We will study how microglia are regulated by sensory experience and in turn how they may impact the perineuronal net, a neuron specific form of the extracellular matrix. The perineuronal net protects cells from oxidate stress and constrains neural alterations in adulthood. How microglia and the perineuronal net interact is unknown and will be the focus of the present study using a synthesis of anatomical, physiological and behavioral experiments.