title: Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex.
abstract: Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA-mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Oded
authors.initials: O
authors.lastname: Klavir
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Matthias
authors.initials: M
authors.lastname: Prigge
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Sarel
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Rony
authors.initials: R
authors.lastname: Paz
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Ofer
authors.identifier: http://orcid.org/0000-0003-4228-1448
authors.initials: O
authors.lastname: Yizhar
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D062308:Optogenetics / Q000379:methods*; D017397:Prefrontal Cortex / Q000502:physiology*