Basolateral Aamygdala circuits for differentiating positive and negative associations

Abstract

The ability to differentiate between rewarding and threatening stimuli, and engaging the appropriate behavioral response is critical for survival. The Basolateral Amygdala (BLA) is an almond shaped structure in the brain where rewarding and fearful associations are encoded by different populations of neurons. However, identifying features of these populations have remained an enigma. My thesis work shows that populations of BLA neurons that differ in their long range anatomical connectivity play opposing roles in the acquisition of positive and negative associations, and dissects a mechanism by which these associations are encoded in the BLA. We show that BLA neurons projecting to the nucleus accumbens (NAc) and BLA neurons projecting to the centromedial nucleus of the amygdala (CeM) undergo opposing changes at their input synapses after rewarding and fearful associations. We then establish the in vivo ramifications of these opposing changes in synaptic strength in response to rewarding and fearful associations by assaying neural activity from BLA neurons and identifying the NAc and CeM projectors. Finally, in order to compare and contrast the role of BLA neural populations in encoding positive and negative associations, we propose a model that parametrizes neural responses to positive and negative cues from large scale electrophysiological recordings. My thesis work identifies functional roles of specific circuit components based on their long range anatomical connectivity, identifies differentially expressed receptors within these circuit components and provides a mechanistic explanation, on synaptic, cellular, circuit and molecular levels, for how positive and negative associations can be formed within, and diverge from the BLA.