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 Relevance Statement
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.
No Sub Projects information available for 5SC3GM122657-07
Publications
Publications are associated with projects, but cannot be identified with any particular year of the project or fiscal year of funding. This is due to the continuous and cumulative nature of knowledge generation across the life of a project and the sometimes long and variable publishing timeline. Similarly, for multi-component projects, publications are associated with the parent core project and not with individual sub-projects.
No Publications available for 5SC3GM122657-07
Patents
No Patents information available for 5SC3GM122657-07
Outcomes
The Project Outcomes shown here are displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed are those of the PI and do not necessarily reflect the views of the National Institutes of Health. NIH has not endorsed the content below.
No Outcomes available for 5SC3GM122657-07
Clinical Studies
No Clinical Studies information available for 5SC3GM122657-07
News and More
Related News Releases
No news release information available for 5SC3GM122657-07
History
No Historical information available for 5SC3GM122657-07
Similar Projects
No Similar Projects information available for 5SC3GM122657-07