Microglial interactions with the Perineuronal Net

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.

Grant Number: 5SC3GM122657-08
NIH Institute/Center: NIH
Principal Investigator: JOSHUA BRUMBERG