A circuit mechanism for differentiating positive and negative associations.
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 and negative. Different populations of BLA neurons may encode fearful or rewarding associations, 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.
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Neuroscience Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Praneeth
P
Namburi
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Anna
A
Beyeler
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 356, Boston, Massachusetts 02115, USA.
Suzuko
S
Yorozu
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Gwendolyn G
GG
Calhoon
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Undergraduate Program in Neuroscience, Wellesley College, Wellesley, Massachusetts 02481, USA.
Sarah A
SA
Halbert
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Romy
R
Wichmann
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Undergraduate Program in Neuroscience, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Stephanie S
SS
Holden
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Master's Program in Biomedical Sciences, University of Amsterdam, Amsterdam 1098 XH, The Netherlands.
Kim L
KL
Mertens
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Undergraduate Program in Neuroscience, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Melodi
M
Anahtar
1] The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA [2] Neuroscience Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Ada C
AC
Felix-Ortiz
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Ian R
IR
Wickersham
Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, NRB 356, Boston, Massachusetts 02115, USA.
Jesse M
JM
Gray
The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Kay M
KM
Tye
D000679:Amygdala / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology* / Q000523:psychology; D020869:Gene Expression Profiling; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009042:Motivation; D009434:Neural Pathways; D009474:Neurons / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D012054:Reinforcement, Psychology; D012201:Reward; D014158:Transcription, Genetic