Parental care is essential for the survival and well-being of young, though parents or other adults sometimes show neglect or aggressive behavior toward infants. While maternal behavior has been studied extensively, agonistic behavior toward infant's remains poorly understood. Our lab has recently demonstrated the power of combining molecular, optogenetic, and behavioral techniques to understand how galanin neurons in the medial preoptic area govern positive aspects of parental behavior (Wu, Autry et al., 2014). In the current application, I plan to expand on this approach to uncover how a population of neurons in the perifornical area of hypothalamus (PeFA) expressing neuropeptide urocortin-3 (ucn3) governs agonistic infant-directed behavior. I found that PeFA neurons are preferentially active during pup-directed aggression, but not parental behavior and the activated neurons largely colocalized with ucn3-expressing neurons. Given the involvement of ucn3 PeFA neurons in anxiety and stress-related behavior combined with my results implicating these neurons in governing pup-directed agonistic behavior, I hypothesize that PeFA ucn3 neurons that normally signal a stressed state are hijacked in some behavioral contexts to negatively impact pup-directed social behavior. The goal of my K99/R00 proposal is to define the anatomy and function of this putative social stress circuit and to connect this anatomy with infant-directe behavior in various physiological states. My long-term goal is to become a leading researcher in the field of neuroscience. I plan to focus on brain centers associated with social behaviors to understand how the brain processes and respond to social stimuli and how this processing becomes disrupted in disease states. I believe that these studies will enhance our understanding of behavioral circuits and create translational inroads for treatment of human disorders. To accomplish this goal, I will need additional training in the most cutting-edge techniques in the field. The future of behavioral circuit analysis such as I am proposing will rely on refined circuit tracing methods, in vivo recording techniques, and manipulating neuronal activity in behavioral contexts. I plan to develop expertise in these techniques during the mentored phase of the award. Under the primary mentorship of Dr. Catherine Dulac, I will learn to use the most sophisticated viral tracing tools available through collaboration with Dr. Liqun Luo and learn to combine optogenetic techniques with tetrode recordings under the co-mentorship of Dr. Nao Uchida. I will seek guidance from a leading expert in stress, Dr. Joseph Mazjoub, and a world- renowned expert in psychiatric disease modeling, Dr. Rene Hen, to take my experiments in a direction with translational potential examining the role of circuits in animal models of Postpartum Depression. With these additional skills gained through support by the NIH K99/R00 Pathway to Independence Award, I will be qualified to execute these goals to make great strides in understanding how social processing becomes disrupted in human psychiatric disorders.
Parental behavior is essential for survival and well-being of young, though parents or other adults sometimes show neglect or aggressive behavior toward infants. Understanding the neural mechanisms governing these agonistic behaviors toward infants will help elucidate how this behavior emerges and illuminate potential therapeutic targets for diseases associated with disrupted parental care such as Major Depressive Disorder and Postpartum Depression.
| Kohl, Johannes; Babayan, Benedicte M; Rubinstein, Nimrod D et al. (2018) Functional circuit architecture underlying parental behaviour. Nature 556:326-331 |
| Kohl, Johannes; Autry, Anita E; Dulac, Catherine (2017) The neurobiology of parenting: A neural circuit perspective. Bioessays 39:1-11 |
| Autry, Anita E (2016) Neurobiology of Chronic Social Defeat Stress: Role of Brain-Derived Neurotrophic Factor Signaling in the Nucleus Accumbens. Biol Psychiatry 80:e39-e40 |
