The Multisensory Ontogeny of Social Behavior

Project Summary
In many mammalian species, infants rely on parental caregiving to survive the vulnerable phase of early
development. Considerable evidence indicates that infants are not just passive recipients of parental care and
maternal separation for even a few hours a day during early postnatal life can lead to profound social deficits in
adult mice. Indeed, it is well established that early life adversity leads to long-lasting sociability deficits in
humans, and developmental sensory processing deficits are closely associated with neurodevelopmental
disorders such as Autism Spectrum Disorder (ASD). Moreover, ASD and other neuropsychiatric disorders are
marked by sex bias in their manifestation, but the sources of this sexual dimorphism is not understood.
Although recent work has revealed mechanistic insights into adult circuit dysfunction induced by early-life
adversity, we know close to nothing about how the infant nervous system encodes parental cues.
Investigations of infant neural processing have been held back by a lack of behavioral paradigms and
technologies to capture and manipulate neural activity and gene expression during the first few days of life. In
preliminary experiments, we have developed a monomolecular odorant induced olfactory imprinting paradigm
which induces a long-lasting appetitive memory of maternal odors experienced during the first few days after
birth. These results provide an opportunity to dissect neural mechanisms underlying valence attachment to
maternal cues and its contributions to the development of social behaviors. Here, we propose to develop a
modular genetic and viral toolkit for the rapid and reversible interrogation of neural activity and gene
expression, allowing us to directly investigate the infant nervous system. We will use these tools to achieve the
following goals: First, we will genetically identify sensory neurons that attach positive valence to neutral
olfactory cues underlying olfactory imprinting. Next, we will use spatial transcriptomics to comprehensively map
neuronal cell-types in the sensory periphery and forebrain of mouse pups and explore the origins of sexual
dimorphisms in early-life social processing. In summary, by combining high resolution behavioral, molecular
and genetic tools, our project will provide the first characterization of ethologically relevant sensory processing
mechanisms in the infant brain and provide insights into the role of maternal cues in the ontogeny of social
behavior.

Grant Number: 1DP2HD118871-01
NIH Institute/Center: NIH
Principal Investigator: Dhananjay Bambah-Mukku