Social interactions with the caregiver, particularly the mother, is a major aspect of early-life experiences. The caregiver provides the infant with critical resources such as nursing, thermoregulation, and safety. Human infants are programmed to emotionally attach to their mothers. The infant-mother bond provides a template for future socialization. However, disruptions in this bond, such as child abuse, can render the infant more vulnerable to neurodevelopmental and psychiatric disorder. As such, understanding how infants emotionally attach to their mothers is a fundamental and unsolved problem in developmental neuroscience. Consequently, investigating how disruptions to these mechanisms affect health is of great significance. My thesis work aims to determine how the early experience of the infant with the mother is integrated in the infant’s brain.
Summary of research
I identify that somatostatin neurons in the zona incerta (ZI-SST neurons) integrate social interactions with the dam in infant mice. Specifically, I use in vivo fiber photometry to measure calcium transients from ZI-SST neurons in preweaning mice. I find that these neurons are activated by contacts with the dam. Furthermore, single-cell calcium imaging reveals the complex encoding of social interactions with the dam within ZI-SST neurons. I then investigate if ZI-SST neurons modulate infant’s behaviors towards the dam. In preweaning mice that are isolated from the dam, activation of ZI-SST neurons buffers infant stress response by suppressing the emission of ultrasonic vocalizations and reducing plasma corticosterone secretion. In contrast, optogenetic inhibition of ZI-SST neurons increased vocalizations in the presence of the dam. These results provide evidence for a novel neural substrate that integrates social interactions with the dam and regulates pup’s physiological and behavioral responses to maternal separation.
Impact of research
The research question I’m studying was previsouly limited due to the lack of efficient methods to record and modulate neural activity in the infant brain. I addressed these challenges by developing innovative methods that overcame these technical limitations. I combined tools of molecular biology, systems neuroscience, and data analysis to develop methods for performing fiber photometry and microendoscopy to record neural activity in infant brain. Additionally, I applied chemogenetics and optogenetics in mouse pups. These methods expanded the application of modern tools to developing brains and opened the door for uncovering questions that were previously restrained by technical limitations.
The increasing prevalence of mental illness can have a significant impact on individuals, families and society as a whole, highlighting the importance of developing efficient prevention and treatment strategies to mitigate the negative consequences of these diseases. The identification of ZI-SST neurons as a responsive node to social experiences with the dam provides a new target to test preventive or interventional behavioral approaches. Future experiments could deliver predictable sequences of activation of ZI-SST neurons using noninvasive optogenetics during sensitive periods, and test if the activation rescues the deficits resulting from rearing under early-life adversity conditions.
The methods and findings of my dissertation work carry great potential benefits for both science and society. The innovative methods can be applied to identify other neural circuits that integrate early-life experiences, ultimately contributing to a better understanding of how the integration happens brain wide. Furthermore, the scientific findings may inform behavioral preventions and interventions that can optimize cognitive and emotional health in developing children, thereby promoting healthier outcomes for individuals and society as a whole.
Future research interests
I’m interested in studying and comparing the nervous system of different species, which will provide valuable insights into the origins of brain functions. For instance, coleoid cephalopods, such as octopuses, have a highly intricate nervous system that evolved independently from vertebrates. Octopuses are known to exhibit complex behaviors, such as mating and aggression, which are well studied in rodent models. However, what fascinates me even more is the unique features of such behaviors in octopuses. For instance, during mating, a female octopus can decide to receive sperms or become aggressive and consume the male. The neural mechanisms underlying these rapid switches in behavior remain elusive, and I am intrigued to determine them in my postdoctoral research