Journal Article

A circuit mechanism for differentiating positive and negative associations

Calhoon, Gwendolyn G., Namburi, Praneeth, Halbert, Sarah A., Anahtar, Melodi, Felix-Ortiz, Ada C., Wichmann, Romy, Gray, Jesse M., Holden, Stephanie S., Tye, Kay M., Wickersham, Ian R., Mertens, Kim L., Beyeler, Anna, Yorozu, Suzuko

2015

Overview

Neurons in the basolateral amygdala projecting to canonical fear or reward circuits undergo opposing changes in synaptic strength following fear or reward conditioning, and selectively activating these projection-target-defined neural populations causes either negative or positive reinforcement, respectively. Positive and negative associations hard-wired in the brain The amygdala is part of the brain important for emotional processing, handling stimuli that have either positive or negative associations — the good and the bad. Little is known about how amygdala neurons differentiate or compartmentalize these distinctions. Here, Kay Tye and colleagues identify the basolateral amygdala (BLA) as a site of divergence for circuits mediating positive and negative emotional or motivational responses. In studies in mice they find that neurons in the BLA projecting to fear or reward circuits undergo opposing changes in synaptic strength following fear or reward conditioning. Selective activation of neural populations causes, respectively, either negative or positive reinforcement. Transcriptome analysis reveals candidate genes that may mediate these functional differences. The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive 1 , 2 and negative 3 , 4 , 5 , 6 , 7 . Different populations of BLA neurons may encode fearful or rewarding associations 8 , 9 , 10 , but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/378/1595/1395 / 631/378/1662 / 631/378/1788 / 631/378/2591/2592 / 82/80 / 82/83 / Amygdala (Brain) / Amygdala - cytology / Amygdala - physiology / Animals / Behavior / Cognition & reasoning / Conditioning, Classical / Emotions / Fear - physiology / Fear - psychology / Gene expression / Gene Expression Profiling / Humanities and Social Sciences / letter / Long-Term Potentiation / Male / Mice / Mice, Inbred C57BL / Morphology / Motivation / multidisciplinary / Neural circuitry / Neural Pathways / Neurological research / Neurology / Neurons - physiology / Nucleus Accumbens - cytology / Nucleus Accumbens - physiology / Nucleus Accumbens - radiation effects / Physiological aspects / Reinforcement (Psychology) / Reward / Science / Transcription, Genetic