Differential fear conditioning generates prefrontal neural ensembles of safety signals

被引:25
作者
Corches, Alex [1 ]
Hiroto, Alex [2 ,3 ]
Bailey, Tyler W. [2 ,3 ]
Speigel, John H., III [2 ,3 ]
Pastore, Justin [2 ,3 ]
Mayford, Mark [4 ]
Korzus, Edward [1 ,2 ,3 ]
机构
[1] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA
[2] Univ Calif Riverside, Dept Psychol, Riverside, CA 92521 USA
[3] Univ Calif Riverside, Program Neurosci, Riverside, CA 92521 USA
[4] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
Medial prefrontal cortex; Fear inhibition; Fear discrimination learning; Memory ensemble; Context-dependent fear conditioning; Fear generalization; FUNCTIONAL CONNECTIVITY; DORSAL HIPPOCAMPUS; PRELIMBIC CORTEX; EXTINCTION; AMYGDALA; MEMORY; NEURONS; EXPRESSION; CONSOLIDATION; MECHANISMS;
D O I
10.1016/j.bbr.2018.11.042
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Fear discrimination is critical for survival, while fear generalization is effective for avoiding dangerous situations. Overgeneralized fear is a typical symptom of anxiety disorders, including generalized anxiety disorder and posttraumatic stress disorder (PTSD). Previous research demonstrated that fear discrimination learning is mediated by prefrontal mechanisms. While the prelimbic (PL) and infralimbic (IL) subdivisions of the medial prefrontal cortex (mPFC) are recognized for their excitatory and inhibitory effects on the fear circuit, respectively, the mechanisms driving fear discrimination are unidentified. To obtain insight into the mechanisms underlying context-specific fear discrimination, we investigated prefrontal neuronal ensembles representing distinct experiences associated with learning to disambiguate between dangerous and similar, but not identical, harmless stimuli. Here, we show distinct quantitative activation differences in response to conditioned and generalized fear experiences, as well as modulation of the neuronal ensembles associated with successful acquisition of context-safety contingencies. These findings suggest that prefrontal neuronal ensembles patterns code functional context-danger and context-safety relationships. The PL subdivision of the mPFC monitors context-danger associations to conditioned fear, whereas differential conditioning sparks additional ensembles associated with the inhibition of generalized fear in both the PL and IL subdivisions of the mPFC. Our data suggest that fear discrimination learning is associated with the modulation of prefrontal subpopulations in a subregion- and experience-specific fashion, and the learning of appropriate responses to conditioned and initially generalized fear experiences is driven by gradual updating and rebalancing of the prefrontal memory representations.
引用
收藏
页码:169 / 184
页数:16
相关论文
共 74 条
[1]  
[Anonymous], 1952, A BEHAV SYSTEM
[2]  
Birrell JM, 2000, J NEUROSCI, V20, P4320
[3]   Context, ambiguity, and unlearning: Sources of relapse after behavioral extinction [J].
Bouton, ME .
BIOLOGICAL PSYCHIATRY, 2002, 52 (10) :976-986
[4]   Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex [J].
Burgos-Robles, Anthony ;
Vidal-Gonzalez, Ivan ;
Santini, Edwin ;
Quirk, Gregory J. .
NEURON, 2007, 53 (06) :871-880
[5]   Sustained Conditioned Responses in Prelimbic Prefrontal Neurons Are Correlated with Fear Expression and Extinction Failure [J].
Burgos-Robles, Anthony ;
Vidal-Gonzalez, Ivan ;
Quirk, Gregory J. .
JOURNAL OF NEUROSCIENCE, 2009, 29 (26) :8474-8482
[6]   A shared neural ensemble links distinct contextual memories encoded close in time [J].
Cai, Denise J. ;
Aharoni, Daniel ;
Shuman, Tristan ;
Shobe, Justin ;
Biane, Jeremy ;
Song, Weilin ;
Wei, Brandon ;
Veshkini, Michael ;
La-Vu, Mimi ;
Lou, Jerry ;
Flores, Sergio E. ;
Kim, Isaac ;
Sano, Yoshitake ;
Zhou, Miou ;
Baumgaertel, Karsten ;
Lavi, Ayal ;
Kamata, Masakazu ;
Tuszynski, Mark ;
Mayford, Mark ;
Golshani, Peyman ;
Silva, Alcino J. .
NATURE, 2016, 534 (7605) :115-+
[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]   Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears [J].
Corcoran, Kevin A. ;
Quirk, Gregory J. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (04) :840-844
[9]   MEDIAL PREFRONTAL CORTEX NEURONAL CIRCUITS IN FEAR BEHAVIOR [J].
Courtin, J. ;
Bienvenu, T. C. M. ;
Einarsson, E. Oe. ;
Herry, C. .
NEUROSCIENCE, 2013, 240 :219-242
[10]   Dissociation in prefrontal cortex of affective and attentional shifts [J].
Dias, R ;
Robbins, TW ;
Roberts, AC .
NATURE, 1996, 380 (6569) :69-72