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- W2891897712 abstract "Author(s): Thomas, Alaina Wren | Advisor(s): Wilbrecht, Linda | Abstract: AbstractThe effects of early life adversity on the development of circuits that support flexible decision-makingbyAlaina Wren ThomasDoctor of Philosophy in NeuroscienceUniversity of California, BerkeleyProfessor Linda Wilbrecht, ChairA large proportion of children in the United States experience childhood adversity, with over 50% reporting at least one adverse event. Early life adversity is strongly associated with increased risk for developing a number of physical and mental health disorders, yet the pathways linking childhood adversity to disease are not well understood. This dissertation explores how the early environment can influence developing neural circuits, with a particular focus on neural circuits that support flexible goal-directed decision-making. Cognitive development plays a significant role in mental illness and prospects for recovery. Flexible decision-making is a major cognitive function that is impaired across multiple neuropsychiatric disorders including bipolar disorder and schizophrenia, that is also critical in supporting behavioral change. In Chapter 2, I review my own collaborative work as well as work from others to describe the distinct developmental trajectories of sub-circuits that support flexible decision-making. I focus on frontal cortex dendritic spines and axonal boutons on afferents and efferents of the frontal cortex. These studies are motivated by the idea that identifying when these circuits grow and/or mature at the synaptic level will inform us when connections may be more vulnerable to adverse experiences and/or when interventions may have the greatest impact. I present in vivo imaging data that support previous classic findings that dendritic spines on frontal pyramidal neurons show loss of linear spine density, or in other words “prune,” across the adolescent period. However, I also present evidence that some long range frontal afferent and efferent circuits continue to grow and add synapses during the adolescent period, while others are pruning and stabilizing. These data refute the simple assumption that frontal circuits globally prune during adolescence, and raise questions about why some circuits show delayed growth.Next, in Chapter 3, I explore how maternal separation, a mouse model of early life adversity, affects flexible decision-making across the lifespan. I find that this early life manipulation leads to changes in decision-making specifically at a juvenile, but not adult life stage. I hypothesize that changes in decision-making strategies at the juvenile time point, a point of first independence, may serve as a cognitive adaptation to signals that indicate a harsh environment. Finally, in Chapter 4, I investigate how maternal separation and more specifically variations in maternal care, impact the development of four long range axons (two afferents and two efferents of the frontal cortex) that each play a role in flexible decision-making. I focus on changes at the adolescent life stage, based on differences in flexible decision-making at this age discussed in Chapter 3. I find that dorsomedial prefrontal cortex (dmPFC) axons that descend to target the basolateral amygdala (BLA) are specifically sensitive to the maternal separation manipulation and variations in maternal care, while the other three axons investigated show no relationship with early life care. Specifically, I found higher bouton density and smaller bouton size on dmPFC-BLA axons in maternally separated mice compared to controls. Additionally, bouton density on this projection correlated with maternal care measures, suggesting early maternal care (P1-10) may scale the later growth of this pathway (at P35). Variations in maternal care may serve as an indicator about the type of environment offspring are growing up in. These data support the idea that the brain can sample the statistics from the early environment and tune specific circuits to adapt to that environment. Taken together, this thesis provides new insights about the development of circuits that support flexible decision-making. Importantly, I demonstrate how early life adversity impacts specific circuits at the synaptic level. These experiments provide high-resolution data that aims to help inform intervention and treatment strategies to promote healthy child development." @default.
- W2891897712 created "2018-09-27" @default.
- W2891897712 creator A5019451174 @default.
- W2891897712 date "2018-01-01" @default.
- W2891897712 modified "2023-09-24" @default.
- W2891897712 title "The effects of early life adversity on the development of circuits that support flexible decision-making" @default.
- W2891897712 cites W1517665341 @default.
- W2891897712 cites W1562703792 @default.
- W2891897712 cites W1838981072 @default.
- W2891897712 cites W1890675559 @default.
- W2891897712 cites W1895368383 @default.
- W2891897712 cites W1927791619 @default.
- W2891897712 cites W1964517848 @default.
- W2891897712 cites W1966155655 @default.
- W2891897712 cites W1966891747 @default.
- W2891897712 cites W1967356584 @default.
- W2891897712 cites W1969819227 @default.
- W2891897712 cites W1971501199 @default.
- W2891897712 cites W1972465236 @default.
- W2891897712 cites W1973851439 @default.
- W2891897712 cites W1976143905 @default.
- W2891897712 cites W1976485053 @default.
- W2891897712 cites W1977573454 @default.
- W2891897712 cites W1978489779 @default.
- W2891897712 cites W1978588905 @default.
- W2891897712 cites W1979237765 @default.
- W2891897712 cites W1979403636 @default.
- W2891897712 cites W1980452424 @default.
- W2891897712 cites W1981451764 @default.
- W2891897712 cites W1982340672 @default.
- W2891897712 cites W1982835526 @default.
- W2891897712 cites W1984427714 @default.
- W2891897712 cites W1984624900 @default.
- W2891897712 cites W1985645068 @default.
- W2891897712 cites W1987550068 @default.
- W2891897712 cites W1987900652 @default.
- W2891897712 cites W1988125482 @default.
- W2891897712 cites W1988287623 @default.
- W2891897712 cites W1989982790 @default.
- W2891897712 cites W1990366708 @default.
- W2891897712 cites W1990956863 @default.
- W2891897712 cites W1991182470 @default.
- W2891897712 cites W1992595542 @default.
- W2891897712 cites W1995485453 @default.
- W2891897712 cites W1997036908 @default.
- W2891897712 cites W1997170756 @default.
- W2891897712 cites W1998980503 @default.
- W2891897712 cites W1999149787 @default.
- W2891897712 cites W2000064453 @default.
- W2891897712 cites W2001528712 @default.
- W2891897712 cites W2001620133 @default.
- W2891897712 cites W2007760226 @default.
- W2891897712 cites W2009155636 @default.
- W2891897712 cites W2009639618 @default.
- W2891897712 cites W2010057415 @default.
- W2891897712 cites W2011562111 @default.
- W2891897712 cites W2012250372 @default.
- W2891897712 cites W2012370457 @default.
- W2891897712 cites W2015455914 @default.
- W2891897712 cites W2016899938 @default.
- W2891897712 cites W2018463951 @default.
- W2891897712 cites W2020073898 @default.
- W2891897712 cites W2020109202 @default.
- W2891897712 cites W2023144165 @default.
- W2891897712 cites W2023448665 @default.
- W2891897712 cites W2023822026 @default.
- W2891897712 cites W2024365408 @default.
- W2891897712 cites W2024392432 @default.
- W2891897712 cites W2024471230 @default.
- W2891897712 cites W2025626596 @default.
- W2891897712 cites W2026108792 @default.
- W2891897712 cites W2026763299 @default.
- W2891897712 cites W2028652183 @default.
- W2891897712 cites W2029318834 @default.
- W2891897712 cites W2030868131 @default.
- W2891897712 cites W2031044889 @default.
- W2891897712 cites W2031167848 @default.
- W2891897712 cites W2031501640 @default.
- W2891897712 cites W2032415515 @default.
- W2891897712 cites W2033114609 @default.
- W2891897712 cites W2035599443 @default.
- W2891897712 cites W2037060007 @default.
- W2891897712 cites W2038112334 @default.
- W2891897712 cites W2040073285 @default.
- W2891897712 cites W2040527392 @default.
- W2891897712 cites W2041144442 @default.
- W2891897712 cites W2043123430 @default.
- W2891897712 cites W2043961643 @default.
- W2891897712 cites W2044191726 @default.
- W2891897712 cites W2045013563 @default.
- W2891897712 cites W2046991951 @default.
- W2891897712 cites W2048142524 @default.
- W2891897712 cites W2048616509 @default.
- W2891897712 cites W2048745224 @default.
- W2891897712 cites W2049641826 @default.
- W2891897712 cites W2049753768 @default.
- W2891897712 cites W2052574702 @default.
- W2891897712 cites W2052798976 @default.
- W2891897712 cites W2054282296 @default.
- W2891897712 cites W2054649184 @default.