Master of Science
Physiology and Pharmacology
The prefrontal cortex (PFC) is one of the cortical areas responsible for complex cognitive abilities, a function that is believed to arise from increased persistent activity within its microcircuits. Activity within microcircuits is regulated by parvalbumin-containing (PV), calbindin-containing (CB), and calretinin-containing (CR) inhibitory interneurons (INs). It remains unclear how the distribution of activity-regulating INs differs across cortical areas such that persistent activity increases specifically within association areas, allowing for their complex functions. This thesis aims to address this gap by characterizing the spatial distributions and differences in relative proportions of INs across early sensory areas and association areas of the common marmoset (Callithrix jacchus). Immunohistochemical analysis of INs across sensory and association areas was performed, followed by manual cell counting. I observed less activity-suppressing PV interneurons and more activity-inducing CR interneurons from sensory areas to PFC. These findings suggest a hierarchical gradient in INs across cortical areas exist and may contribute to the mechanism underlying PFC’s functions.
Summary for Lay Audience
The prefrontal cortex (PFC) is an association area of the outer division of the brain, the cortex, involved in regulating thoughts, decisions, and actions through connections with other brain areas. A region within the PFC, known as the dorsolateral PFC (LPFC), is involved in temporary storage of information while the brain uses that information. This is an ability known as working memory (WM) and can guide our decisions and behaviours. While many species have WM ability, primates demonstrate advanced WM capabilities. WM ability is thought to be associated with increased levels of activity within LPFC compared with other brain areas. At the cellular level, increased activity in LPFC compared with sensory areas is thought to arise, at least in part, from differences in the abundances of specific cells responsible for regulating activity levels across the cortex, known as interneurons (INs), but the exact nature of such changes in cellular abundance across brain areas remains unclear. Given that different types of INs have different effects on overall activity levels, this project aimed to compare distributions and proportions of different INs between other sensory and association areas to understand the cellular mechanism underlying increased LPFC activity levels during WM in primates, specifically in marmosets in the context of this project. The findings revealed an increase in activity-promoting IN and a decrease in activity-inhibiting IN relative proportion from early areas to LPFC, providing support for the theory that changes in IN proportions may be involved in the emergence of increased LPFC activity during WM.
Khajehdehi, Nika, "Characterizing the Spatial Distribution of Inhibitory Interneurons Across Early Sensory and Association Areas in Callithrix jacchus" (2023). Electronic Thesis and Dissertation Repository. 9864.
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