Sensory deprivation from mice to man has been shown to have profound impacts on neuronal physiology, behavior and cognitive processes. Underling these changes are alterations in neuronal and non-neuronal structures. Our preliminary data shows that following one month of whisker trimming induced sensory deprivation the perineuronal net (PN), a neuron specific form of the extra cellular matrix, is significantly reduced in the barrel cortex of mice. The loss of the PN is most prominent around fast-spiking parvalbumin positive GABAergic interneurons. Converging evidence has shown that fast-spiking interneurons play a pivotal role in the closure of the developmental critical period in the visual system and their proper functioning is necessary for the proper physiological functioning of the cortex. Coincident with deprivation induced decreases in the PN we observed increases in the enzyme tissue plasminogen activator (tPA) which dissolves the PN. Under the same conditions microglia become activated, thus we propose that sensory deprivation induces microglia activation which release tPA and thus decrease the PN.
In Aim 1 we will demonstrate a causal link between sensory deprivation, microglia activation and tPA release resulting in PN decreases using immunocytochemical techniques in conjunction with stereology.
In Aim 2 we will focus on the physiological roll PNs have in modifying the intrinsic and synaptic properties of fast-spiking interneurons. We will employ our novel small volume incubator which allows for time dependent degradation of the PN in conjunction with dual whole-cell recordings.

Public Health Relevance

Sensory experience can have a profound impact on neuronal development in humans. Using a mouse model we will examine the link between sensory experience and the resultant biochemical and physiological changes in the brain. These studies will lead to insights about brain development and how sensory experience can impact its trajectory.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Continuance Award (SC3)
Project #
5SC3GM122657-04
Application #
9897604
Study Section
Special Emphasis Panel (ZGM1)
Program Officer
Krasnova, Irina N
Project Start
2017-05-01
Project End
2021-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Queens College
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
619346146
City
Flushing
State
NY
Country
United States
Zip Code
11367