R01MH128745
Project Grant
Overview
Grant Description
Identity of Late-Maturing Amygdala Neurons in Humans and Mice - Project Summary/Abstract
Adolescence is a key window for social/emotional development in humans. This period is characterized by growth of the amygdala, which increases in both size and neuron number. We recently described a unique form of neurodevelopment in the human amygdala paralaminar nuclei (PL). This region contains a population of immature neurons that develop on a delayed timeline relative to other neurons. These neurons mature during adolescence when they will form excitatory neurons.
In preliminary studies in the mouse, a tractable animal model, we found a population of immature neurons that share molecular, anatomical, and morphological features with late-developing neurons in humans. Additionally, the timeline of their maturation appears similar in both species. Although they remain immature during postnatal ages, these late-maturing neurons are born during embryonic neurogenesis.
The goal of this proposal is to uncover the development, synaptic integration, and molecular diversity of late-maturing amygdala neurons from genesis to functional integration using both humans and mice. Using a combination of state-of-the-art approaches, we propose to accomplish this goal by:
1) Tracking the embryonic and postnatal developmental dynamics of late-maturing PL neurons in mice (Specific Aim 1).
2) Identifying when and how late-maturing amygdala neurons functionally integrate into existing amygdala circuitry in mice (Specific Aim 2).
3) Uncovering and comparing late-maturing PL neuron molecular diversity in mice and humans (Specific Aim 3).
In this cross-species project, we will address major questions about the development and maturation of an unexplored form of neuron development that occurs during the critical stage of adolescence. This work is an essential first step for future studies of the role of these neurons in social/emotional behavior, mechanisms controlling their delayed development, and their significance to human behavioral pathophysiology.
Adolescence is a key window for social/emotional development in humans. This period is characterized by growth of the amygdala, which increases in both size and neuron number. We recently described a unique form of neurodevelopment in the human amygdala paralaminar nuclei (PL). This region contains a population of immature neurons that develop on a delayed timeline relative to other neurons. These neurons mature during adolescence when they will form excitatory neurons.
In preliminary studies in the mouse, a tractable animal model, we found a population of immature neurons that share molecular, anatomical, and morphological features with late-developing neurons in humans. Additionally, the timeline of their maturation appears similar in both species. Although they remain immature during postnatal ages, these late-maturing neurons are born during embryonic neurogenesis.
The goal of this proposal is to uncover the development, synaptic integration, and molecular diversity of late-maturing amygdala neurons from genesis to functional integration using both humans and mice. Using a combination of state-of-the-art approaches, we propose to accomplish this goal by:
1) Tracking the embryonic and postnatal developmental dynamics of late-maturing PL neurons in mice (Specific Aim 1).
2) Identifying when and how late-maturing amygdala neurons functionally integrate into existing amygdala circuitry in mice (Specific Aim 2).
3) Uncovering and comparing late-maturing PL neuron molecular diversity in mice and humans (Specific Aim 3).
In this cross-species project, we will address major questions about the development and maturation of an unexplored form of neuron development that occurs during the critical stage of adolescence. This work is an essential first step for future studies of the role of these neurons in social/emotional behavior, mechanisms controlling their delayed development, and their significance to human behavioral pathophysiology.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Pittsburgh,
Pennsylvania
152133203
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 382% from $708,993 to $3,417,257.
University Of Pittsburgh - Of The Commonwealth System Of Higher Education was awarded
Late-Maturing Amygdala Neurons in Humans and Mice
Project Grant R01MH128745
worth $3,417,257
from the National Institute of Mental Health in July 2022 with work to be completed primarily in Pittsburgh Pennsylvania United States.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.242 Mental Health Research Grants.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 5/21/26
Period of Performance
7/1/22
Start Date
4/30/27
End Date
Funding Split
$3.4M
Federal Obligation
$0.0
Non-Federal Obligation
$3.4M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01MH128745
Transaction History
Modifications to R01MH128745
Additional Detail
Award ID FAIN
R01MH128745
SAI Number
R01MH128745-3258026980
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Other
Awarding Office
75N700 NIH National Institute of Mental Health
Funding Office
75N700 NIH National Institute of Mental Health
Awardee UEI
MKAGLD59JRL1
Awardee CAGE
1DQV3
Performance District
PA-12
Senators
Robert Casey
John Fetterman
John Fetterman
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of Mental Health, National Institutes of Health, Health and Human Services (075-0892) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,388,428 | 100% |
Modified: 5/21/26