and Abstract Specificity is a key characteristic of adult memory that emerges during early childhood. The neural mechanisms responsible for the ontogeny of memory specificity are unknown. Our lab and others have previously hypothesized that features of hippocampal development may regulate the transition from memory generalization to specificity during childhood. In line with this hypothesis, our lab has identified the development of the extracellular matrix ? and in particular, perineuronal nets ? as a potential regulator of memory specificity. This proposal will provide critical insight into the role of perineuronal nets in regulating the ontogeny of memory specificity.
Aim 1 will use a cutting-edge optogenetic approach to elucidate how generalized versus specific memories are differentially represented in cellular memory engrams in the hippocampus.
Aim 2 will use viral gene manipulation approach to reveal the critical requirement of perineuronal net protein HAPLN1 for memory specificity during adulthood.
Aim 3 will use a complementary viral approach to examine whether HAPLN1 expression in the hippocampus of infants is sufficient to trigger to onset of memory specificity. This proposal will reveal for the first time a role for the extracellular matrix in regulating the development of memory functions, namely memory specificity. It will provide fundamental knowledge about the function of perineuronal nets in memory specificity, which may provide novel avenues for understanding and treating multiple brain disorders characterized by inappropriate memory generalization, such as generalized anxiety, depressive, and post-traumatic stress disorders.

Public Health Relevance

This proposal will characterize how the development of perineuronal nets in in the hippocampus contributes to the ontogeny of memory specificity. It will dissect how generalized versus specific memories are differentially represented by neuronal ensembles across development and the role of link protein HAPLN1 in the early transition from memory generalization to specificity. This proposal will identify the brain extracellular matrix as a key regulator of memory development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31MH120920-02
Application #
10132730
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Pinard, Courtney
Project Start
2019-09-01
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Toronto
Department
Type
DUNS #
259999779
City
Toronto
State
ON
Country
Canada
Zip Code
M5 1S8