Dissecting amygdala cell types in fear and extinction

The mammalian brain consists of billions of neurons; Individual neurons serve as building blocks (Cajal 1911, translation Swanson and Swanson 1995). However, studying individual neurons is simply insufficient to understand how the brain works. A promising approach is the cell-type-specific approach, an effort to classify neurons that perform the same function as a single cell type (functional definition, see (Luo et al., 2008)) and to understand their roles in information processing and behavioral outputs. Nevertheless, the limitation of this definition is that we barely know the precise functions or roles of neurons, and even in very well-characterized neurons such as retinal ganglion cells, there would likely be remaining unknown functions. Thus, as an operational definition to drive neuroscience forward, defining cell types using genetic tools that allow us to access specific subsets of neurons was suggested and widely accepted in an almost implicit manner. This consensus is based on an optimistic view that, at some point, the operational genetic definition and the ultimate functional definition would converge.
In this thesis, having this philosophy in mind, I try to match several operationally defined amygdala cell types with their distinct functions/roles in the context of fear and extinction learning. In Project 1, I demonstrate that a cell-type in the amygdala complex defined by molecular marker expression exerts essential functions in fear and extinction by composing a unique mutual inhibition circuit motif. In Project 2, I find that a cell-type in the basolateral amygdala defined by di-synaptic downstream target show unprecedented functional specificity in fear learning. Finally, in Project 3, I aim to characterize functions and roles of cell types in the basolateral amygdala defined by dynamic, neuronal activity-dependent gene expression upon learning.
Collectively, this thesis serves as an important stepping stone to achieving the convergence between definitions of a cell type.