Volume 81, Issue 2, 22 January 2014, Pages 428–437
Long-range connectivity defines behavioral specificity of amygdala neurons.
Senn V1, Wolff SB1, Herry C2, Grenier F2, Ehrlich I2, Gründemann J2, Fadok JP2, Müller C2, Letzkus JJ2, Lüthi A3.
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.