The Role of Corticolimbic Circuits in Maternal Behavior - PROJECT ABSTRACT/SUMMARY The transition to motherhood brings dramatic changes in physiology and brain function. This includes changes to neural circuits regulating maternal care, threat and stress responses, which are essential for the survival and well-being of the offspring. Human and animal studies highlight the importance of resilient threat and stress responses to efficient maternal care. Clinical work suggests that improving emotional states of the mother is promising for engaging more successfully with her progeny. Corticolimbic circuits play a crucial role in threat and stress responses. However, little is known about the interactions between corticolimbic circuitry and core maternal brain regions, making it challenging to relate threat and stress responses to maternal care. To address this gap in knowledge, we recently developed an approach to study corticolimbic brain regions. We uncovered a distinct subpopulation of neurons within corticolimbic circuits that regulate maternal care, threat and stress responses in the postpartum state. Our research will yield new insights into corticolimbic regulation of maternal behaviors by defining the circuit, synaptic function and transcriptional mechanisms using a combination of genetic technologies, neural-circuit dissection, synaptic electrophysiology as well as biochemical and transcriptional tools. These approaches allow for a close examination of links between cell- signaling, synapses and the neuronal nucleus within a specific cell population in relationship to the maternal state. In Aim 1 we identify cell populations in corticolimbic areas responsible for maternal care and threat responses postpartum, using chemogenetics, optogenetics, cell-type specific gene promoters, novel knock-in mouse lines and viral vectors not previously tested in maternal behavior. In Aim 2 we define the synaptic mechanisms behind maternal behaviors postpartum. We will conduct a detailed analysis of key synaptic proteins, synaptic transmission and synaptic plasticity in corticolimbic circuits. Accomplishing aim will connect neural circuits (studied in Aim 1) with synaptic mechanisms that are part of a key intracellular signaling pathway that supports maternal care and threat responses postpartum. In Aim 3 we make some of the first measurements of transcription in corticolimbic circuits postpartum. We will examine expression of candidate genes in relevant brain regions for mothers of our newly developed transgenic mouse lines and compare these genes to synaptic molecules studied in Aim 2 and to gene databases of human mental disorders with similar neuronal mechanisms. Accomplishing Aim 3 will provide a mechanistic foundation for connecting corticolimbic circuits (studied in Aim 1), synaptic proteins and synaptic function (studied in Aim 2) with maternal care and threat responses and will be a source of new gene targets to test this connection. The results of this work will guide neural circuit-based, gene-based and pharmacological strategies for improving mothers’ well-being and their ability to take care of their offspring.
