Long-range connectivity defines behavioral specificity of amygdala neurons.
Memories are acquired and encoded within large-scale neuronal networks spanning different brain areas. The anatomical and functional specificity of such long-range interactions and their role in learning is poorly understood. The amygdala and the medial prefrontal cortex (mPFC) are interconnected brain structures involved in the extinction of conditioned fear. Here, we show that a defined subpopulation of basal amygdala (BA) projection neurons targeting the prelimbic (PL) subdivision of mPFC is active during states of high fear, whereas BA neurons targeting the infralimbic (IL) subdivision are recruited, and exhibit cell-type-specific plasticity, during fear extinction. Pathway-specific optogenetic manipulations demonstrate that the activity balance between pathways is causally involved in fear extinction. Together, our findings demonstrate that, although intermingled locally, long-range connectivity defines distinct subpopulations of amygdala projection neurons and indicate that the formation of long-term extinction memories depends on the balance of activity between two defined amygdala-prefrontal pathways.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, 4000 Basel, Switzerland.
Verena
V
Senn
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, 4000 Basel, Switzerland.
Steffen B E
SB
Wolff
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Cyril
C
Herry
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
François
F
Grenier
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Ingrid
I
Ehrlich
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Jan
J
Gründemann
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Jonathan P
JP
Fadok
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Christian
C
Müller
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Johannes J
JJ
Letzkus
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland. Electronic address: andreas.luthi@fmi.ch.
Andreas
A
Lüthi
D000161:Acoustic Stimulation / Q000009:adverse effects; D000200:Action Potentials / Q000235:genetics / Q000502:physiology; D000679:Amygdala / Q000166:cytology*; D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D055592:Biophysical Phenomena / Q000187:drug effects / Q000502:physiology; D001703:Biophysics; D002452:Cell Count; D000075402:Channelrhodopsins; D003214:Conditioning, Classical; D004546:Elapid Venoms / Q000494:pharmacology; D004558:Electric Stimulation; D005108:Extinction, Psychological; D005239:Fear / Q000523:psychology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D062308:Optogenetics; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology; D013997:Time Factors
D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D004546:Elapid Venoms; D008164:Luminescent Proteins; D016761:Oncogene Proteins v-fos; D010455:Peptides; C054562:yellow fluorescent protein, Bacteria; C020273:dendrotoxin; C064719:iberiotoxin