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.

Project Narrative Infants represent one of the most vulnerable members of society and considerable resources are devoted to their healthy development, but we know surprisingly little about how their brains process social information from primary caregivers. This project is aimed at understanding the sensory encoding of maternal cues in the infant brain and its contribution to adult social behavior. This is relevant to the mission of the NIH due to its potential to reveal mechanisms underlying sensory neuron dysfunction underlying neurodevelopental disorders and sex biases in their manifestation.