(236) Functional and Genetic Dissection of Central Amygdala Neurons Underlying Sensory and Aversive Components of Itch

Abstract

Itch is defined as an unpleasant sensation that evokes a desire to scratch. The supraspinal mechanisms that are engaged in itch processing are largely unknown. Here we took an unbiased approach using immediate early gene (cFos) mapping for precise dissection of brain circuits that mediate itch processing. These studies identified the central nucleus of the amygdala (CeA) as a region robustly engaged during itch/scratching. To explore this directly, we recorded real time calcium dynamics using fiber photometry in freely behaving mice and found that scratching led to robust increase in CeA neuronal activity in animals exposed to pruritic stimuli. To gain genetic access to CeA neurons that are engaged in itch processing, we used activity-dependent genetic labeling of neurons that are activated by pruritic stimuli. We manipulated the activity of these itch responsive neurons in the CeA using optogenetics or chemogenetics to study the role of these neurons in pruritus. We found that activation of itch responsive neurons in the CeA induced itch-like behaviors as well as robust real time place aversion, while inhibiting these neurons reduced itch-like behaviors. Transcriptional profiling of these itch-responsive CeA neurons identified a number of genes that encode neuropeptides, neurotransmitters and receptors that will enable a detailed understanding of the molecular phenotype of these neurons and how these CeA neurons form part of the network that relays real-time information about the both sensory and affective aspects of itch.