Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent-infant bonding, however, the exact signaling mechanisms used by oxytocin in the brain are not well understood. The oxytocin receptor is a G protein-coupled receptor that is expressed at two weeks of postnatal life, a time period of heightened plasticity and inhibitory circuit maturation, which is promoted by BDNF. Here we report an interplay between oxytocin and the BDNF TrkB receptor that occurs in the cortex within 15-30 minutes of oxytocin treatment. Receptors for oxytocin and BDNF overlap in their distribution in different brain regions, especially in areas important for learning and memory. Oxytocin's ability to transactivate TrkB receptors is independent of BDNF transcription and release. In the next grant period, we will focus upon the mechanism of TrkB receptor transactivation via oxytocin by studying the cellular mechanisms of action of oxytocin receptors in the rodent brain. We hypothesize that synaptic strength and cortical plasticity may be regulated by the dual actions of oxytocin and TrkB receptor signaling. The long-term effects of oxytocin may be due to crosstalk with the BDNF TrkB receptor. The transactivation of TrkB receptors by oxytocin may affect synaptic changes, and re-balance excitation and inhibition and maintain network stability. Our investigation is directly relevant to understanding the mechanism of trophic factors and their impact upon neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's, Huntington's and Alzheimer's diseases, as well as neuropsychiatric disorders, such as autism, anxiety, depression and schizophrenia.
Oxytocin and BDNF are important neuropeptides that are responsible for many higher order activities, such as learning, memory, plasticity and social behavior. We have found that oxytocin can transactivate the BDNF TrkB receptor, leading to an increase in receptor signaling activity. A mechanistic understanding of the role of oxytocin in receptor transactivation is relevant to several neuropsychiatric problems, such as autism, epilepsy, anxiety, depression and neurodegeneration.
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