Molecular and Circuit Organization of Amygdalostriatal Circuits Controlling Valence Behaviors
- Howe, James Robinson
- Advisor(s): Root, Cory
Abstract
This dissertation characterizes the composition and functional relevance of selected extended amygdala transition regions involved in valence behaviors. Chapter 1 introduces the basis of innately valenced behaviors and its relationship to the cortical amygdala and explores possible implications of observed innate valence behaviors. Chapter 2 uses electrophysiology, calcium imaging, optogenetics, and single-nucleus RNA-sequencing to characterize the molecular and electrophysiological composition of the amygdalostriatal transition region and the adjacent central amygdala and striatal regions and identify distinct features of each in either domain. These approaches find that the amygdalostriatal transition area is enriched for Drd2-expressing MSNs compared to surrounding regions, and the activity of the region’s Drd2+ neurons, which is necessary for conditioned fear responses, encodes learned negative valence for stimuli, identifying a critical role for the amygdalostriatal transition area in motivated behaviors, especially with regard to negative valence. Chapter 3 uses optogenetics, chemogenetics, single-nucleus RNA-sequencing, and long-range projection tracing to identify a functional topography for valence in the posterolateral cortical amygdala, characterize its molecular cell types and downstream outputs, and examine the relationship between these three modalities. This work shows that plCoA contains dissociable, topographically biased pathways projecting to either the medial amygdala or the nucleus accumbens, and these circuits respectively control innate olfactory attraction and aversion. Overall, these findings add to our understanding of the composition of these extended amygdala subregions, their function, and the unique features of each necessary to exert their behavioral effects.