Prefrontal inputs to the amygdala instruct fear extinction memory formation

被引:195
作者
Bukalo, Olena [1 ,2 ]
Pinard, Courtney R. [1 ]
Silverstein, Shana [1 ,2 ]
Brehm, Christina [3 ,4 ]
Hartley, Nolan D. [5 ]
Whittle, Nigel [3 ,4 ]
Colacicco, Giovanni [1 ]
Busch, Erica [1 ]
Patel, Sachin [5 ]
Singewald, Nicolas [3 ,4 ]
Holmes, Andrew [1 ]
机构
[1] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD 20853 USA
[2] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA
[3] Univ Innsbruck, Dept Pharmacol & Toxicol, Inst Pharm, A-6020 Innsbruck, Austria
[4] Univ Innsbruck, Ctr Mol Biosci Innsbruck, A-6020 Innsbruck, Austria
[5] Vanderbilt Univ, Med Ctr, Dept Psychiat & Mol Physiol & Biophys, Nashville, TN 37232 USA
基金
奥地利科学基金会;
关键词
D O I
10.1126/sciadv.1500251
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Persistent anxiety after a psychological trauma is a hallmark of many anxiety disorders. However, the neural circuits mediating the extinction of traumatic fear memories remain incompletely understood. We show that selective, in vivo stimulation of the ventromedial prefrontal cortex (vmPFC)-amygdala pathway facilitated extinction memory formation, but not retrieval. Conversely, silencing the vmPFC-amygdala pathway impaired extinction formation and reduced extinction-induced amygdala activity. Our data demonstrate a critical instructional role for the vmPFC-amygdala circuit in the formation of extinction memories. These findings advance our understanding of the neural basis of persistent fear, with implications for posttraumatic stress disorder and other anxiety disorders.
引用
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页数:8
相关论文
共 46 条
[1]
Synaptic correlates of fear extinction in the amygdala [J].
Amano, Taiju ;
Unal, Cagri T. ;
Pare, Denis .
NATURE NEUROSCIENCE, 2010, 13 (04) :489-U112
[2]
Physiological identification and infralimbic responsiveness of rat intercalated amygdala neurons [J].
Amir, Alon ;
Amano, Taiju ;
Pare, Denis .
JOURNAL OF NEUROPHYSIOLOGY, 2011, 105 (06) :3054-3066
[3]
SUBTHALAMIC NUCLEUS EVOKES SIMILAR LONG LASTING GLUTAMATERGIC EXCITATIONS IN PALLIDAL, ENTOPEDUNCULAR AND NIGRAL NEURONS IN THE BASAL GANGLIA SLICE [J].
Ammari, R. ;
Lopez, C. ;
Bioulac, B. ;
Garcia, L. ;
Hammond, C. .
NEUROSCIENCE, 2010, 166 (03) :808-818
[4]
[Anonymous], 2013, DSM 5 DIAGN STAT MAN
[5]
Synaptology of prefrontal cortical projections to the basolateral amygdala: An electron microscopic study in the rat [J].
BrinleyReed, M ;
Mascagni, F ;
McDonald, AJ .
NEUROSCIENCE LETTERS, 1995, 202 (1-2) :45-48
[6]
Different Fear States Engage Distinct Networks within the Intercalated Cell Clusters of the Amygdala [J].
Busti, Daniela ;
Geracitano, Raffaella ;
Whittle, Nigel ;
Dalezios, Yannis ;
Manko, Miroslawa ;
Kaufmann, Walter ;
Saetzler, Kurt ;
Singewald, Nicolas ;
Capogna, Marco ;
Ferraguti, Francesco .
JOURNAL OF NEUROSCIENCE, 2011, 31 (13) :5131-5144
[7]
Synaptic Encoding of Fear Extinction in mPFC-amygdala Circuits [J].
Cho, Jun-Hyeong ;
Deisseroth, Karl ;
Bolshakov, Vadim Y. .
NEURON, 2013, 80 (06) :1491-1507
[8]
Revisiting the Role of Infralimbic Cortex in Fear Extinction with Optogenetics [J].
Do-Monte, Fabricio H. ;
Manzano-Nieves, Gabriela ;
Quinones-Laracuente, Kelvin ;
Ramos-Medina, Liorimar ;
Quirk, Gregory J. .
JOURNAL OF NEUROSCIENCE, 2015, 35 (08) :3607-3615
[9]
Amygdala Microcircuits Controlling Learned Fear [J].
Duvarci, Sevil ;
Pare, Denis .
NEURON, 2014, 82 (05) :966-980
[10]
Fitzgerald PJ, 2015, MOL PSYCHIATR, V20, P901, DOI 10.1038/mp.2014.161