Grant: Canada Research Chairs
Carleton University
$100,000.00
Developmental Neuroscience
FY 2024-25
Summary
High levels of synaptogenesis and synaptic plasticity during early life render the immature brain particularly vulnerable to early-life experience influences. Early-life experiences (i.e., stress and seizures) have been known to induce long-lasting impacts on neural network development and later-life cognitive functions, including social memory and social behaviors. How early-life experiences regulate brain development and the associated social behaviors remains elusive. The previously overlooked hippocampal subregion CA2 has recently emerged as an essential player in social memory and social behavior. It is important to note that the structural and physiological heterogeneity across the neurons in hippocampus has been recognized as a critical factor determining hippocampal functions. Therefore, clarifying the heterogenous activity of immature CA2 neurons is crucial to further understanding the effects of early life experience on brain development.
Using a novel activity-dependent labeling and chemogenetic manipulation system, we aim to examine the role of early-life experience-activated hippocampal CA2 neurons in its long-term effects on neural circuit development and social behaviors. To achieve this aim, we will first establish the impacts of early-life experience on neuronal activation in hippocampal CA2 (Aim 1). We will then determine to what extent early-life experience induces changes in excitatory and inhibitory circuits in hippocampal CA2 neurons using whole-cell patch clamp recordings (Aim 2). Finally, we will investigate whether early-life experience-activated CA2 neurons mediate changes in brain development and social behaviors by using chemogenetic tools to precisely modulate the activity of the selective subpopulation of hippocampal CA2 neurons (Aim 3).
These experiments will advance our understanding of the role of CA2 neurons in mediating the effects of early-life experience on brain development, providing cellular and molecular mechanistic insights into early-life experience and social behaviors.
Program
Canada Research Chairs
Recipient
Location
Ontario, Canada
Recipient Type
Academia
Type
Grant
Source
NSERC's Awards Data
As published
Application id
CRC-2021-00186
Name nom
Sun, Hongyu
Department département
Department of Neuroscience - Carleton University
Organization id
23
Institution établissement
Carleton University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2024
Competition year année de concours
2021
Award amount
100000
Program id
CRC
Program name en
Canada Research Chairs
Program name fr
Chaires de recherche du Canada
Group en
DISCOVERY RESEARCH
Group fr
RECHERCHE AXÉE SUR LA DÉCOUVERTE
Committee code
9998
Committee name en
Canada Research Chair Selection Committee
Committee name fr
Comité de sélection des Chaires de recherche du Canada
Area of application code
9999
Area of application group en
Not available
Area of application group fr
Non disponible
Area of application en
Not available
Area of application fr
Non disponible
Research subject code
9999
Research subject group en
Not available
Research subject group fr
Non disponible
Research subject en
Not available
Research subject fr
Non disponible
Field of research list codes
RDF3010414
Field of research list names en
Neurodegeneration
Field of research list names fr
Neurodégénérescence
Socioeconomic objective list codes
RDS10799
Socioeconomic objective list names en
Health, n.e.c.
Socioeconomic objective list names fr
Santé, n.c.a.
Application title
Developmental Neuroscience
Keywords
hippocampus; synaptic transmission; social behavior; Brain development; Early life experience; CA2
Application summary
High levels of synaptogenesis and synaptic plasticity during early life render the immature brain particularly vulnerable to early-life experience influences. Early-life experiences (i.e., stress and seizures) have been known to induce long-lasting impacts on neural network development and later-life cognitive functions, including social memory and social behaviors. How early-life experiences regulate brain development and the associated social behaviors remains elusive. The previously overlooked hippocampal subregion CA2 has recently emerged as an essential player in social memory and social behavior. It is important to note that the structural and physiological heterogeneity across the neurons in hippocampus has been recognized as a critical factor determining hippocampal functions. Therefore, clarifying the heterogenous activity of immature CA2 neurons is crucial to further understanding the effects of early life experience on brain development.
Using a novel activity-dependent labeling and chemogenetic manipulation system, we aim to examine the role of early-life experience-activated hippocampal CA2 neurons in its long-term effects on neural circuit development and social behaviors. To achieve this aim, we will first establish the impacts of early-life experience on neuronal activation in hippocampal CA2 (Aim 1). We will then determine to what extent early-life experience induces changes in excitatory and inhibitory circuits in hippocampal CA2 neurons using whole-cell patch clamp recordings (Aim 2). Finally, we will investigate whether early-life experience-activated CA2 neurons mediate changes in brain development and social behaviors by using chemogenetic tools to precisely modulate the activity of the selective subpopulation of hippocampal CA2 neurons (Aim 3).
These experiments will advance our understanding of the role of CA2 neurons in mediating the effects of early-life experience on brain development, providing cellular and molecular mechanistic insights into early-life experience and social behaviors.
