Molecular mechanisms of infantile learning and memory

Project Summary
Behavioral studies have shown that early life experience significantly shapes the development of brain abilities.
Accordingly, if early experiences are highly unbalanced, e.g. if they occur under the influence of chronic
challenges or stresses, the individual's personality will develop specific traits, including some that are
associated with severe psychopathologies. Despite these extensive behavioral characterizations, very little is
known about the biological mechanisms underlying learning and memory in early life, with the exception
of the effects of trauma and stress. Understanding the mechanisms underlying learning and memory in
early development is key for comprehending how the learning and memory systems are built and
function throughout life, as well as to better elucidate the deficits associated to neurodevelopmental
disabilities.
One of the most important systems operating in the brain is the medial temporal lobe-dependent memory
system, which processes information about episodic, spatial, contextual and social experiences. Until recently
it was believed that this memory system does not function in infancy because it is developmentally immature,
and only begins to be involved late in development. However, recent studies in rodent models, including our
own, showed that episodic and spatial forms of learning require the function of biological mechanisms in the
dorsal hippocampus (dHC), a main region, together with the medial prefrontal cortex (mPFC), of the medial
temporal lobe memory system. Despite this recent progress, knowledge of the biological and system-level
mechanisms of infantile, hippocampus-dependent learning and memory is lacking.
To fill this knowledge gap we propose to employ rodent models of episodic and spatial learning, genetically
engineered mouse models, molecular imaging technology, spatial transcriptomics and RiboTag mouse
technology combined with omic analyses to pursue the following specific aims: (1) To map the distribution at
a system level (dHC and mPFC) of the cellular networks activated in response to episodic learning in infancy
and in memory recovery following reminders at later ages, and to test the malleability and roles of recovered
infantile memories in adult behavior. (2) To comprehensively profile in situ dHC and mPFC gene expression at
the level of the whole transcriptome, as well as obtain a comprehensive translatome specifically regulated in
excitatory and inhibitory neurons, in response to learning in both infant and adult brains.
These experiments will provide an unprecedented amount of novel information regarding the biological and
system-level mechanisms underlying infantile learning and memory, as well as an invaluable source of
knowledge for generating novel hypotheses regarding neurodevelopmental and adult cognitive disorders.

Grant Number: 5R01HD103641-04
NIH Institute/Center: NIH
Principal Investigator: CRISTINA ALBERINI