Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Front. Med.    2022, Vol. 16 Issue (4) : 518-539    https://doi.org/10.1007/s11684-022-0941-2
REVIEW
Prefrontal cortical circuits in anxiety and fear: an overview
Yihua Chen(), Nengyuan Hu, Jianming Yang, Tianming Gao()
State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong−Hong Kong−Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China
 Download: PDF(3335 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Pathological anxiety is among the most difficult neuropsychiatric diseases to treat pharmacologically, and it represents a major societal problem. Studies have implicated structural changes within the prefrontal cortex (PFC) and functional changes in the communication of the PFC with distal brain structures in anxiety disorders. Treatments that affect the activity of the PFC, including cognitive therapies and transcranial magnetic stimulation, reverse anxiety- and fear-associated circuit abnormalities through mechanisms that remain largely unclear. While the subjective experience of a rodent cannot be precisely determined, rodent models hold great promise in dissecting well-conserved circuits. Newly developed genetic and viral tools and optogenetic and chemogenetic techniques have revealed the intricacies of neural circuits underlying anxiety and fear by allowing direct examination of hypotheses drawn from existing psychological concepts. This review focuses on studies that have used these circuit-based approaches to gain a more detailed, more comprehensive, and more integrated view on how the PFC governs anxiety and fear and orchestrates adaptive defensive behaviors to hopefully provide a roadmap for the future development of therapies for pathological anxiety.
Keywords prefrontal cortex      anxiety      fear      neural circuits      optogenetics      DREADD     
Corresponding Author(s): Yihua Chen,Tianming Gao   
About author:

Tongcan Cui and Yizhe Hou contributed equally to this work.
Just Accepted Date: 20 June 2022   Online First Date: 09 August 2022    Issue Date: 02 September 2022
 Cite this article:   
Yihua Chen,Nengyuan Hu,Jianming Yang, et al. Prefrontal cortical circuits in anxiety and fear: an overview[J]. Front. Med., 2022, 16(4): 518-539.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0941-2
https://academic.hep.com.cn/fmd/EN/Y2022/V16/I4/518
Fig.1  Validated tests for evaluating anxiety and fear in mice. (A) Anxiety in mice is measured behaviorally through various tests, which are highlighted in yellow. (B) Examples of fear assays are highlighted in orange.
Fig.2  Potential approaches for cell- and projection-specific modulation of neuronal activity using optogenetics and DREADDs. (A,B) Categories of single-component optogenetic (A) and chemogenetic (B) tools; transported ions, signaling pathways and potential downstream neuronal effects of activation. (C) Targeting a population by using promoter-specific AAV and somatic or terminal manipulation. (D) Additional cell-type specificity is attained by injecting a recombinase-dependent virus into a transgenic animal expressing a recombinase, such as Cre or Flp in specific cells. (E) Intersectional AAV strategy to limit AAV vector expression to a discrete projection population. The color of the syringes and the projection lines indicate different virus injected and traced.
　　Neuromodulatory approach Target population Effect Test
ACC [89] 　　eNpHR: 5 mW, constant Glutamatergic neurons No effect OFT
　　ChR2: 10 ms, 10 Hz, 0.2 mW Glutamatergic neurons No effect OFT
PL [81] 　　eNpHR: 6–9 mW, constant Glutamatergic neurons Anxiogenic OFT, EPM
　　ChR2: 20 Hz, 6–9 mW Glutamatergic neurons No effect OFT, EPM
PL [85] 　　ChR2: 15 ms, 10 Hz, 5 mW, 1 min 　　off/1 min on for 60 min Glutamatergic neurons No effect NSFT
IL [85] 　　ChR2: 15 ms, 10 Hz, 5 mW, 1 min 　　off/1 min on for 60 min Glutamatergic neurons Anxiolytic NSFT
IL [80] 　　eNpHR: 6–9 mW, constant Glutamatergic neurons Anxiolytic OFT, EPM
　　ChR2: 5 ms, 20 Hz, 3 mW Glutamatergic neurons Anxiogenic OFT, EPM
DP [80] 　　ChR2: 5 ms, 20 Hz, 3 mW Glutamatergic neurons Anxiolytic OFT, EPM
mPFC [79] 　　ChR2: 40 ms, 100 Hz, 1–2 mW Glutamatergic neurons No effect EPM
mPFC [78] 　　Gq DREADD: 2.5 mg/kg CNO Glutamatergic neurons No effect OFT
mPFC [93] 　　Gq DREADD: 0.5 mg/kg CNO, 30 min 　　before the test PV neurons No effect OFT, NSFT
　　Gq DREADD: 0.5 mg/kg CNO, 3 weeks PV neurons No effect OFT, NSFT
dmPFC [94] 　　Gi DREADD: 5 mg/kg CNO, 30 min 　　before the test SST neurons Anxiogenic OFT, EPM, NSFT
　　Gi DREADD: 0.5 mg/kg CNO, 3 weeks SST neurons Anxiolytic OFT, EPM, NSFT
vmPFC [82] 　　eNpHR: 10 mW, constant Glutamatergic neurons No effect OFT, EPM
　　ChR2: 10 ms, 10 Hz, 1 mW Glutamatergic No effect OFT, EPM
　　ChR2: 10 ms, 10 Hz, 1 mW vmPFCBMA-projecting neurons Anxiolytic OFT, EPM
vmPFC [83] 　　ChR2: 15 ms, 10 Hz, 5 mW, 1 min 　　off/1 min on for 60 min Drd1+ glutamatergic neurons Anxiolytic OFT, NSFT
Drd2+ glutamatergic neurons No effect OFT, NSFT
Tab.1  Overview of studies that employed optogenetic/chemogenetic techniques to manipulate cells somas in the PFC in studies of anxiety
Fig.3  Prefrontal circuits in anxiety. (A) Sagittal view of rodent brain including afferent and efferent circuits of mPFC implicated in anxiety-related behaviors. (B) Sophisticated circuitry linked to anxiety. (C) mPFC cellular populations implicated in anxiety-related behaviors. The two lines of the arrow: the color of the upper line refers to the brain region, and the color of the lower line refers to the cell type. Acc, anterior cingulate cortex; BLA, basolateral amygdala; BNST, bed nucleus of the stria terminalis; CeA, central amygdala; Cg1, cingulate cortex, area 1; dmPFC, dorsal medial prefrontal cortex; DP, dorsal peduncular cortex; IL, infralimbic cortex; LS, lateral septum; MD, medial dorsal thalamus; mPFC, medial prefrontal cortex; PL, prelimbic cortex; vHPC, ventral hippocampus; vmPFC, ventral medial prefrontal cortex; D1, Drd1-expressing pyramidal cells; D2, Drd2-expressing pyramidal cells; SST, somatostatin-expressing neurons; PV, parvalbumin-expressing neurons; AS, acute stimulation; CS, chronic stimulation.
Neuromodulatory approach Target population Effect Test
Jhang et al. [89] eNpHR: 5 mW, constant ACC–BLA No effect OFT
ChR2: 10 ms, 10 Hz, 0.5 mW ACC–BLA No effect OFT
Chenet al. [80] eNpHR: 10 mW, constant and Gi DREADD: 5 μmol/L CNO IL–LSIL–CeA AnxiolyticAnxiogenic OFT, EPMOFT, EPM
ChR2: 5 ms, 20 Hz, 3–15 mW (according to the target) IL–LSIL–CeA AnxiogenicAnxiolytic OFT, EPMOFT, EPM
IL–BLA No effect OFT, EPM
IL–BNST No effect OFT, EPM
Adhikari et al. [82] eNpHR: 10 mW, constant vmPFC–amygdala Anxiogenic OFT, EPM
ChR2: 5 ms, 10 Hz dmPFC–amygdala No effect OFT, EPM
vmPFC–amygdala Anxiolytic OFT, EPM
Hare et al. [83] ChR2: 15 ms, 10 Hz, 5 mW, 1 min off/1 min on for 60 min vmPFCDrd1+–BLA Anxiolytic NSFT
Tab.2  Overview of studies that employed optogenetic/chemogenetic techniques to manipulate PFC efferent targeting in studies of anxiety
Neuromodulatory approach Target population Effect Test
Parfitt et al. [105] Gi DREADD: 1 mg/kg CNO vHPCmPFC-projecting Anxiolytic OFT, EPM, NSFT
Gq DREADD: 3 mg/kg CNO vHPCmPFC-projecting Anxiogenic OFT, EPM, NSFT
Coreano et al. [106] ArchT: 10 mW, every 2 min vHPC?mPFC Anxiolytic OFT, EPM, NSFT
MD?mPFC No effect EPM
Ortiz et al. [111] eNpHR: 5 mW, constant BLA?mPFC Anxiolytic OFT
ChR2: 5 ms, 20 Hz, 5 mW BLA?mPFC Anxiogenic OFT, EPM
Tab.3  Overview of studies that employed optogenetic/chemogenetic techniques to manipulate mPFC afferent targeting in studies of anxiety
Neuromodulatory approach Target population Effect Test
ACC [89] eNpHR: 5 mW, constant Glutamatergic neurons Freezing↑ Innate fear
Retrieval: no effect Aud FC
ChR2: 10 ms, 10 Hz, 0.2 mW Glutamatergic neurons Freezing↓ Innate fear
Retrieval: impaired Aud FC and Ctx FC
ACCBLA-projecting neurons Freezing↓ Innate fear
ACC [125] eNpHR: 8–10 mW, constant ACCCA-projecting neurons Retrieval: impaired Ctx FC
Retrieval: no effect Aud FC
PL [114] eNpHR: 63.7–127.4 mW/mm2, constant Neurons Extinction retrieval: no effect Aud FC
PL [112] eNpHR: 5 mW, constant Glutamatergic neurons Retrieval (6 h and 7 days): impaired Aud FC
PL [126] ChR2: 15 ms, 30 Hz, 159 mW/mm2 Glutamatergic neurons Extinction: no effect Aud FC
PL [127] ArchT: constant, 6–9 mW SST neurons Training: no effect but impaired retrieval the next day Aud FC
Retrieval: impaired Aud FC
ChR2: 10 ms, 20 Hz, 6–9 mW SST neurons Retrieval: no effect Aud FC
PL [128] PSAM DREADD: 5 mg/kg PSEM308 PV neurons Training: no effect but impaired retrieval the next day tFC and Ctx FC
Retrieval: no effect tFC and Ctx FC
Extinction: no effect tFC and Ctx FC
Extinction retrieval: no effect tFC
Gi DREADD: 5 mg/kg CNO PLIL-projecting neurons Training: no effect tFC
Extinction: no effect tFC
IL [80] eNpHR: 10 mW, constant Glutamatergic neurons Retrieval: no effect Aud FC
Extinction: no effect but impaired extinction retrieval the next day Aud FC
ChR2: 5 ms, 20 Hz, 3 mW Glutamatergic neurons Retrieval: impaired Aud FC
Extinction: facilitated Aud FC
IL [118] eNpHR: 8–10 mW, constant Glutamatergic neurons Extinction: no effect but impaired extinction retrieval the next day Aud FC
Extinction retrieval: no effect Aud FC
ChR2: 5 ms, 20 Hz, 5 mW Glutamatergic neurons Retrieval: impaired Aud FC
Extinction: facilitated Aud FC
Extinction retrieval: facilitated Aud FC
IL [114] eNpHR: 63.7–127.4 mW/mm2, constant Neurons Retrieval: no effect Aud FC
Extinction retrieval: impaired Aud FC
Glutamatergic neurons Extinction: no effect Aud FC
ChR2: 20 ms, 10 Hz, 6.4 mW/mm2 Glutamatergic neurons Extinction retrieval: facilitated Aud FC
IL [129] Gi DREADD: 5 mg/kg CNO PV neurons Extinction: facilitated Aud FC
Gq DREADD: 5 mg/kg CNO PV neurons Extinction: impaired Aud FC
IL [128] PSAM DREADD: 5 mg/kg PSEM308 PV neurons Training: no effect tFC and Ctx FC
Retrieval: no effect tFC and Ctx FC
Extinction: impaired tFC and Ctx FC
Extinction retrieval: no effect tFC
Gi DREADD: 5 mg/kg CNO ILPL-projecting neurons Training: no effect tFC
Extinction: impaired tFC
mPFC [117] KORD-DREADD: 17 mg/kg mPFCBLA-projecting neurons Extinction: no effect but impaired extinction retrieval the next day Aud FC
dmPFC [130] ChR2: 4 Hz, 10 mW PV neurons Freezing↑ Innate fear
dmPFC [131] ArchT: 250 ms light pulse PV neurons Retrieval: fear promoted Aud FC
Extinction: impaired Aud FC
ChR2: 250 ms light pulse PV neurons Retrieval: impaired Aud FC
vmPFC [82] ChR2: 10 ms, 10 Hz, 1 mW Glutamatergic neurons Extinction: no effect but facilitated extinction retrieval the next day Aud FC
vmPFCBMA-projecting neurons Extinction: no effect but facilitated extinction retrieval the next day Aud FC
vmPFC [116] Gi-DREADD: 3 mg/kg CNO VmPFCRE-projecting neurons Extinction: impaired Aud FC
Extinction retrieval: impaired Aud FC
Tab.4  Overview of studies that use optogenetic/chemogenetic techniques to manipulate cell somas in the PFC in studies of fear
Fig.4  Prefrontal circuits in fear. (A) Sagittal view of rodent brain, including afferent and efferent circuits of mPFC implicated in fear-related behaviors. (B) Sophisticated circuitry linked to fear. (C) dmPFC cellular response and regulation from amygdala under fear-related behaviors. The thickness of the arrow indicates the strength of regulation. ACC, anterior cingulate cortex; BA, basal amygdala; BLA, basolateral amygdala; Cg1, cingulate cortex, area 1; CeA, central amygdala; CeL, lateral subdivision of the central amygdala; CeM, centromedial subdivision of the amygdala; dmPFC, dorsal medial prefrontal cortex; DP, dorsal peduncular cortex; IL, infralimbic cortex; LS, lateral septum; PL, prelimbic cortex; PVT, paraventricular thalamus; vHPC, ventral hippocampus; RE, thalamic nucleus reuniens; PY, pyramidal neurons; SST, somatostatin-expressing neurons; PV, parvalbumin-expressing neurons.
Neuromodulatory approach Target population Effect Test
Jhang et al. [89] eNpHR: 5 mW, constant ACC–BLA Freezing↑ Innate fear
PL–BLA No effect Innate fear
ChR2: 10 ms, 10 Hz, 0.5 mW ACC–BLA Freezing↓ Innate fear
Do-Monte et al. [112] eNpHR: 10 mW, constant PL–BLA Retrieval (6 h): impaired Aud FC
Retrieval (7 days): no effect Aud FC
PL –PVT Retrieval (6 h): no effect Aud FC
Retrieval (7 days): impaired Aud FC
Marek et al. [126] eNpHR: constant PL–IL Extinction: impaired Aud FC
ChR2: 15 ms, 30 Hz, 159 mW/mm2 PL–IL Extinction: facilitated Aud FC
Mukherjee et al. [128] Gi-DREADD: 5 mg/kg CNO PL–IL Extinction: no effect tFC
IL–PL Extinction: impaired tFC
Ramanathan et al. [116] Gi-DREADD: 1 mmol/L CNO PL–RE Extinction retrieval: impaired Aud FC
IL–RE Extinction retrieval: impaired Aud FC
mPFC–RE Extinction retrieval: impaired Aud FC
Gi-DREADD: 5 μmol/L CNO IL–LS Retrieval: no effect Aud FC
Extinction: facilitated Aud FC
IL–CeA Retrieval: no effect Aud FC
Extinction: impaired Aud FC
ChR2: 5 ms, 20 Hz, 7–15 mW IL–LS Retrieval: no effect Aud FC
Extinction: impaired Aud FC
IL–CeA Retrieval: no effect Aud FC
Extinction: facilitated Aud FC
IL–CeL Retrieval: no effect Aud FC
Extinction: no effect Aud FC
IL–CeM Retrieval: no effect Aud FC
Extinction: facilitated Aud FC
Adhikari et al. [82] ChR2: 10 ms, 10 Hz, 10 mW dmPFC–amygdala Acquisition: no effect Aud FC
Extinction: no effect but impaired extinction retrieval the next day Aud FC
Retrieval: no effect Ctx FC
vmPFC–amygdala Acquisition: no effect Aud FC
Extinction: facilitated Aud FC
Retrieval: impaired Ctx FC
Bukalo et al. [132] eNpHR: 10 mW, constant vmPFC–amygdala Extinction: no effect but impaired extinction retrieval the next day Aud FC
Extinction retrieval: no effect Aud FC
ChR2: 10 ms, 10 Hz, 10 mW vmPFC–amygdala Extinction: no effect but facilitated extinction retrieval the next day Aud FC
Extinction retrieval: no effect Aud FC
Tab.5  Overview of studies that used optogenetic/chemogenetic techniques for the manipulation of PFC efferent targeting in studies of fear
Neuromodulatory approach Target population Effect Test
Marek et al. [144] Gi DREADD: 1–3 mg/kg vHPCIL-projecting neurons Renewal: impaired Aud FC
Gq DREADD: 1–3 mg/kg vHPCIL-projecting neurons Renewal: promoted Aud FC
Senn et al. [141] eNpHR: 10 mW, constant BAIL-projecting neurons Extinction: no effect but impaired extinction retrieval the next day Aud FC
BAPL-projecting neurons Extinction: no effect but facilitated extinction retrieval the next day Aud FC
Klavir et al. [142] ChETA: 9 s burst of 100 Hz, 3 ms pulse every 60 s for 15 min BLA–PLBLA–IL Extinction: facilitatedExtinction: facilitated Aud FCAud FC
Tab.6  Overview of studies that used optogenetic/chemogenetic techniques for the manipulation of mPFC afferent targeting in studies of fear
1 DW Grupe, JB Nitschke. Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nat Rev Neurosci 2013; 14( 7): 488– 501
https://doi.org/10.1038/nrn3524 pmid: 23783199
2 M Davis, DL Walker, L Miles, C Grillon. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 2010; 35( 1): 105– 135
https://doi.org/10.1038/npp.2009.109 pmid: 19693004
3 RC Kessler, M Petukhova, NA Sampson, AM Zaslavsky, HU Wittchen. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 2012; 21( 3): 169– 184
https://doi.org/10.1002/mpr.1359 pmid: 22865617
4 HU Wittchen, F Jacobi, J Rehm, A Gustavsson, M Svensson, B Jönsson, J Olesen, C Allgulander, J Alonso, C Faravelli, L Fratiglioni, P Jennum, R Lieb, A Maercker, Os J van, M Preisig, L Salvador-Carulla, R Simon, HC Steinhausen. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21( 9): 655– 679
https://doi.org/10.1016/j.euroneuro.2011.07.018 pmid: 21896369
5 D Chisholm, K Sweeny, P Sheehan, B Rasmussen, F Smit, P Cuijpers, S Saxena. Scaling-up treatment of depression and anxiety: a global return on investment analysis. Lancet Psychiatry 2016; 3( 5): 415– 424
https://doi.org/10.1016/S2215-0366(16)30024-4 pmid: 27083119
6 RC Kessler, WT Chiu, O Demler, KR Merikangas, EE Walters. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62( 6): 617– 627
https://doi.org/10.1001/archpsyc.62.6.617 pmid: 15939839
7 RC Kessler, P Berglund, O Demler, R Jin, KR Merikangas, EE Walters. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62( 6): 593– 602
https://doi.org/10.1001/archpsyc.62.6.593 pmid: 15939837
8 Y Lecrubier. Widespread underrecognition and undertreatment of anxiety and mood disorders: results from 3 European studies. J Clin Psychiatry 2007; 68(Suppl 2): 36–41
pmid: 17288506
9 B Bandelow, S Michaelis, D Wedekind. Treatment of anxiety disorders. Dialogues Clin Neurosci 2017; 19( 2): 93– 107
https://doi.org/10.31887/DCNS.2017.19.2/bbandelow pmid: 28867934
10 B Bandelow, M Reitt, C Röver, S Michaelis, Y Görlich, D Wedekind. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol 2015; 30( 4): 183– 192
https://doi.org/10.1097/YIC.0000000000000078 pmid: 25932596
11 AN Kaczkurkin, EB Foa. Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence. Dialogues Clin Neurosci 2015; 17( 3): 337– 346
https://doi.org/10.31887/DCNS.2015.17.3/akaczkurkin pmid: 26487814
12 Z Wang, SPH Whiteside, L Sim, W Farah, AS Morrow, M Alsawas, P Barrionuevo, M Tello, N Asi, B Beuschel, L Daraz, J Almasri, F Zaiem, L Larrea-Mantilla, OJ Ponce, A LeBlanc, LJ Prokop, MH Murad. Comparative effectiveness and safety of cognitive behavioral therapy and pharmacotherapy for childhood anxiety disorders: a systematic review and meta-analysis. JAMA Pediatr 2017; 171( 11): 1049– 1056
https://doi.org/10.1001/jamapediatrics.2017.3036 pmid: 28859190
13 JK Carpenter, LA Andrews, SM Witcraft, MB Powers, JAJ Smits, SG Hofmann. Cognitive behavioral therapy for anxiety and related disorders: a meta-analysis of randomized placebo-controlled trials. Depress Anxiety 2018; 35( 6): 502– 514
https://doi.org/10.1002/da.22728 pmid: 29451967
14 MM Zugliani, MC Cabo, AE Nardi, G Perna, RC Freire. Pharmacological and neuromodulatory treatments for panic disorder: clinical trials from 2010 to 2018. Psychiatry Investig 2019; 16( 1): 50– 58
https://doi.org/10.30773/pi.2018.12.21.1 pmid: 30696238
15 RC Freire, C Cabrera-Abreu, R Milev. Neurostimulation in anxiety disorders, post-traumatic stress disorder, and obsessive-compulsive disorder. Adv Exp Med Biol 2020; 1191 : 331– 346
https://doi.org/10.1007/978-981-32-9705-0_18 pmid: 32002936
16 S Deppermann, N Vennewald, J Diemer, S Sickinger, FB Haeussinger, S Notzon, I Laeger, V Arolt, AC Ehlis, P Zwanzger, AJ Fallgatter. Does rTMS alter neurocognitive functioning in patients with panic disorder/agoraphobia? An fNIRS-based investigation of prefrontal activation during a cognitive task and its modulation via sham-controlled rTMS. BioMed Res Int 2014; 2014 : 542526
https://doi.org/10.1155/2014/542526 pmid: 24757668
17 DA Clark, AT Beck. Cognitive theory and therapy of anxiety and depression: convergence with neurobiological findings. Trends Cogn Sci 2010; 14( 9): 418– 424
https://doi.org/10.1016/j.tics.2010.06.007 pmid: 20655801
18 DE Linden. How psychotherapy changes the brain—the contribution of functional neuroimaging. Mol Psychiatry 2006; 11( 6): 528– 538
https://doi.org/10.1038/sj.mp.4001816 pmid: 16520823
19 T Raij, A Nummenmaa, MF Marin, D Porter, S Furtak, K Setsompop, MR Milad. Prefrontal cortex stimulation enhances fear extinction memory in humans. Biol Psychiatry 2018; 84( 2): 129– 137
https://doi.org/10.1016/j.biopsych.2017.10.022 pmid: 29246436
20 A Chocyk, I Majcher-Maślanka, D Dudys, A Przyborowska, K Wędzony. Impact of early-life stress on the medial prefrontal cortex functions—a search for the pathomechanisms of anxiety and mood disorders. Pharmacol Rep 2013; 65( 6): 1462– 1470
https://doi.org/10.1016/S1734-1140(13)71506-8 pmid: 24552993
21 B Myers-Schulz, M Koenigs. Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders. Mol Psychiatry 2012; 17( 2): 132– 141
https://doi.org/10.1038/mp.2011.88 pmid: 21788943
22 SL Thompson-Schill, J Jonides, C Marshuetz, EE Smith, M D’Esposito, IP Kan, RT Knight, D Swick. Effects of frontal lobe damage on interference effects in working memory. Cogn Affect Behav Neurosci 2002; 2( 2): 109– 120
https://doi.org/10.3758/CABN.2.2.109 pmid: 12455679
23 JD Bremner. Traumatic stress: effects on the brain. Dialogues Clin Neurosci 2006; 8( 4): 445– 461
https://doi.org/10.31887/DCNS.2006.8.4/jbremner pmid: 17290802
24 I Liberzon, B Martis. Neuroimaging studies of emotional responses in PTSD. Ann N Y Acad Sci 2006; 1071( 1): 87– 109
https://doi.org/10.1196/annals.1364.009 pmid: 16891565
25 LM Shin, SL Rauch, RK Pitman. Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci 2006; 1071( 1): 67– 79
https://doi.org/10.1196/annals.1364.007 pmid: 16891563
26 SE Bruce, KR Buchholz, WJ Brown, L Yan, A Durbin, YI Sheline. Altered emotional interference processing in the amygdala and insula in women with post-traumatic stress disorder. Neuroimage Clin 2013; 2 : 43– 49
https://doi.org/10.1016/j.nicl.2012.11.003 pmid: 24179757
27 L Brinkmann, C Buff, K Feldker, SV Tupak, MPI Becker, MJ Herrmann, T Straube. Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder. Psychol Med 2017; 47( 15): 2675– 2688
https://doi.org/10.1017/S0033291717001192 pmid: 28485259
28 TM Ball, S Sullivan, T Flagan, CA Hitchcock, A Simmons, MP Paulus, MB Stein. Selective effects of social anxiety, anxiety sensitivity, and negative affectivity on the neural bases of emotional face processing. Neuroimage 2012; 59( 2): 1879– 1887
https://doi.org/10.1016/j.neuroimage.2011.08.074 pmid: 21920442
29 C Buff, C Schmidt, L Brinkmann, B Gathmann, S Tupak, T Straube. Directed threat imagery in generalized anxiety disorder. Psychol Med 2018; 48( 4): 617– 628
https://doi.org/10.1017/S0033291717001957 pmid: 28735579
30 I Labuschagne, KL Phan, A Wood, M Angstadt, P Chua, M Heinrichs, JC Stout, PJ Nathan. Medial frontal hyperactivity to sad faces in generalized social anxiety disorder and modulation by oxytocin. Int J Neuropsychopharmacol 2012; 15( 7): 883– 896
https://doi.org/10.1017/S1461145711001489 pmid: 21996304
31 HY Wang, XX Zhang, CP Si, Y Xu, Q Liu, HT Bian, BW Zhang, XL Li, ZR Yan. Prefrontoparietal dysfunction during emotion regulation in anxiety disorder: a meta-analysis of functional magnetic resonance imaging studies. Neuropsychiatr Dis Treat 2018; 14 : 1183– 1198
https://doi.org/10.2147/NDT.S165677 pmid: 29785110
32 A Etkin, TD Wager. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry 2007; 164( 10): 1476– 1488
https://doi.org/10.1176/appi.ajp.2007.07030504 pmid: 17898336
33 CM Sylvester, M Corbetta, ME Raichle, TL Rodebaugh, BL Schlaggar, YI Sheline, CF Zorumski, EJ Lenze. Functional network dysfunction in anxiety and anxiety disorders. Trends Neurosci 2012; 35( 9): 527– 535
https://doi.org/10.1016/j.tins.2012.04.012 pmid: 22658924
34 AF Arnsten, MA Raskind, FB Taylor, DF Connor. The effects of stress exposure on prefrontal cortex: translating basic research into successful treatments for post-traumatic stress disorder. Neurobiol Stress 2015; 1 : 89– 99
https://doi.org/10.1016/j.ynstr.2014.10.002 pmid: 25436222
35 Z Long, C Medlock, M Dzemidzic, YW Shin, AW Goddard, U Dydak. Decreased GABA levels in anterior cingulate cortex/medial prefrontal cortex in panic disorder. Prog Neuropsychopharmacol Biol Psychiatry 2013; 44 : 131– 135
https://doi.org/10.1016/j.pnpbp.2013.01.020 pmid: 23391588
36 G Hasler, AC Nugent, PJ Carlson, RE Carson, M Geraci, WC Drevets. Altered cerebral γ-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by [11C]flumazenil positron emission tomography. Arch Gen Psychiatry 2008; 65( 10): 1166– 1175
https://doi.org/10.1001/archpsyc.65.10.1166 pmid: 18838633
37 MJ Herrmann, A Katzorke, Y Busch, D Gromer, T Polak, P Pauli, J Deckert. Medial prefrontal cortex stimulation accelerates therapy response of exposure therapy in acrophobia. Brain Stimul 2017; 10( 2): 291– 297
https://doi.org/10.1016/j.brs.2016.11.007 pmid: 27931887
38 M Balconi, C Ferrari. Left DLPFC rTMS stimulation reduced the anxiety bias effect or how to restore the positive memory processing in high-anxiety subjects. Psychiatry Res 2013; 209( 3): 554– 559
https://doi.org/10.1016/j.psychres.2013.03.032 pmid: 23601793
39 E Makovac, DR Watson, F Meeten, SN Garfinkel, M Cercignani, HD Critchley, C Ottaviani. Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety. Soc Cogn Affect Neurosci 2016; 11( 11): 1719– 1728
https://doi.org/10.1093/scan/nsw091 pmid: 27369066
40 YH Jung, JE Shin, YI Lee, JH Jang, HJ Jo, SH Choi. Altered amygdala resting-state functional connectivity and hemispheric asymmetry in patients with social anxiety disorder. Front Psychiatry 2018; 9 : 164
https://doi.org/10.3389/fpsyt.2018.00164 pmid: 29755374
41 J Lipka, M Hoffmann, WH Miltner, T Straube. Effects of cognitive-behavioral therapy on brain responses to subliminal and supraliminal threat and their functional significance in specific phobia. Biol Psychiatry 2014; 76( 11): 869– 877
https://doi.org/10.1016/j.biopsych.2013.11.008 pmid: 24393393
42 PR Goldin, M Ziv, H Jazaieri, K Hahn, R Heimberg, JJ Gross. Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: randomized clinical trial. JAMA Psychiatry 2013; 70( 10): 1048– 1056
https://doi.org/10.1001/jamapsychiatry.2013.234 pmid: 23945981
43 C Andreescu, LK Sheu, D Tudorascu, JJ Gross, S Walker, L Banihashemi, H Aizenstein. Emotion reactivity and regulation in late-life generalized anxiety disorder: functional connectivity at baseline and post-treatment. Am J Geriatr Psychiatry 2015; 23( 2): 200– 214
https://doi.org/10.1016/j.jagp.2014.05.003 pmid: 24996397
44 C Belzung, G Griebel. Measuring normal and pathological anxiety-like behaviour in mice: a review. Behav Brain Res 2001; 125( 1-2): 141– 149
https://doi.org/10.1016/S0166-4328(01)00291-1 pmid: 11682105
45 JF Cryan, A Holmes. The ascent of mouse: advances in modelling human depression and anxiety. Nat Rev Drug Discov 2005; 4( 9): 775– 790
https://doi.org/10.1038/nrd1825 pmid: 16138108
46 DJ Anderson, R Adolphs. A framework for studying emotions across species. Cell 2014; 157( 1): 187– 200
https://doi.org/10.1016/j.cell.2014.03.003 pmid: 24679535
47 S Pellow, P Chopin, SE File, M Briley. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985; 14( 3): 149– 167
https://doi.org/10.1016/0165-0270(85)90031-7 pmid: 2864480
48 AK Kraeuter, PC Guest, Z Sarnyai. The open field test for measuring locomotor activity and anxiety-like behavior. Methods Mol Biol 2019; 1916 : 99– 103
https://doi.org/10.1007/978-1-4939-8994-2_9 pmid: 30535687
49 C Ambrogi Lorenzini, C Bucherelli, A Giachetti. Passive and active avoidance behavior in the light-dark box test. Physiol Behav 1984; 32( 4): 687– 689
https://doi.org/10.1016/0031-9384(84)90327-5 pmid: 6484018
50 SC Dulawa, KA Holick, B Gundersen, R Hen. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 2004; 29( 7): 1321– 1330
https://doi.org/10.1038/sj.npp.1300433 pmid: 15085085
51 Z Merali, C Levac, H Anisman. Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice. Biol Psychiatry 2003; 54( 5): 552– 565
https://doi.org/10.1016/S0006-3223(02)01827-9 pmid: 12946884
52 C Shang, Z Liu, Z Chen, Y Shi, Q Wang, S Liu, D Li, P Cao. A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice. Science 2015; 348( 6242): 1472– 1477
https://doi.org/10.1126/science.aaa8694 pmid: 26113723
53 H Yang, J Yang, W Xi, S Hao, B Luo, X He, L Zhu, H Lou, YQ Yu, F Xu, S Duan, H Wang. Laterodorsal tegmentum interneuron subtypes oppositely regulate olfactory cue-induced innate fear. Nat Neurosci 2016; 19( 2): 283– 289
https://doi.org/10.1038/nn.4208 pmid: 26727549
54 KM Myers, M Davis. Mechanisms of fear extinction. Mol Psychiatry 2007; 12( 2): 120– 150
https://doi.org/10.1038/sj.mp.4001939 pmid: 17160066
55 P Tovote, JP Fadok, A Lüthi. Neuronal circuits for fear and anxiety. Nat Rev Neurosci 2015; 16( 6): 317– 331
https://doi.org/10.1038/nrn3945 pmid: 25991441
56 BM Graham, MR Milad. The study of fear extinction: implications for anxiety disorders. Am J Psychiatry 2011; 168( 12): 1255– 1265
https://doi.org/10.1176/appi.ajp.2011.11040557 pmid: 21865528
57 JD Bremner, B Elzinga, C Schmahl, E Vermetten. Structural and functional plasticity of the human brain in posttraumatic stress disorder. Prog Brain Res 2007; 167 : 171– 186
https://doi.org/10.1016/S0079-6123(07)67012-5 pmid: 18037014
58 S Duvarci, D Pare. Amygdala microcircuits controlling learned fear. Neuron 2014; 82( 5): 966– 980
https://doi.org/10.1016/j.neuron.2014.04.042 pmid: 24908482
59 GG Calhoon, KM Tye. Resolving the neural circuits of anxiety. Nat Neurosci 2015; 18( 10): 1394– 1404
https://doi.org/10.1038/nn.4101 pmid: 26404714
60 K Deisseroth. Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 2015; 18( 9): 1213– 1225
https://doi.org/10.1038/nn.4091 pmid: 26308982
61 O Yizhar, LE Fenno, TJ Davidson, M Mogri, K Deisseroth. Optogenetics in neural systems. Neuron 2011; 71( 1): 9– 34
https://doi.org/10.1016/j.neuron.2011.06.004 pmid: 21745635
62 SM Sternson, BL Roth. Chemogenetic tools to interrogate brain functions. Annu Rev Neurosci 2014; 37( 1): 387– 407
https://doi.org/10.1146/annurev-neuro-071013-014048 pmid: 25002280
63 BN Armbruster, X Li, MH Pausch, S Herlitze, BL Roth. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci USA 2007; 104( 12): 5163– 5168
https://doi.org/10.1073/pnas.0700293104 pmid: 17360345
64 DJ Urban, BL Roth. DREADDs (designer receptors exclusively activated by designer drugs): chemogenetic tools with therapeutic utility. Annu Rev Pharmacol Toxicol 2015; 55( 1): 399– 417
https://doi.org/10.1146/annurev-pharmtox-010814-124803 pmid: 25292433
65 JL Gomez, J Bonaventura, W Lesniak, WB Mathews, P Sysa-Shah, LA Rodriguez, RJ Ellis, CT Richie, BK Harvey, RF Dannals, MG Pomper, A Bonci, M Michaelides. Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Science 2017; 357( 6350): 503– 507
https://doi.org/10.1126/science.aan2475 pmid: 28774929
66 EJ Kremer, S Boutin, M Chillon, O Danos. Canine adenovirus vectors: an alternative for adenovirus-mediated gene transfer. J Virol 2000; 74( 1): 505– 512
https://doi.org/10.1128/JVI.74.1.505-512.2000 pmid: 10590140
67 AR Nectow, EJ Nestler. Viral tools for neuroscience. Nat Rev Neurosci 2020; 21( 12): 669– 681
https://doi.org/10.1038/s41583-020-00382-z pmid: 33110222
68 D Zimmermann, A Zhou, M Kiesel, K Feldbauer, U Terpitz, W Haase, T Schneider-Hohendorf, E Bamberg, VL Sukhorukov. Effects on capacitance by overexpression of membrane proteins. Biochem Biophys Res Commun 2008; 369( 4): 1022– 1026
https://doi.org/10.1016/j.bbrc.2008.02.153 pmid: 18331832
69 E Moser, I Mathiesen, P Andersen. Association between brain temperature and dentate field potentials in exploring and swimming rats. Science 1993; 259( 5099): 1324– 1326
https://doi.org/10.1126/science.8446900 pmid: 8446900
70 MA Long, MS Fee. Using temperature to analyse temporal dynamics in the songbird motor pathway. Nature 2008; 456( 7219): 189– 194
https://doi.org/10.1038/nature07448 pmid: 19005546
71 M Mahn, M Prigge, S Ron, R Levy, O Yizhar. Biophysical constraints of optogenetic inhibition at presynaptic terminals. Nat Neurosci 2016; 19( 4): 554– 556
https://doi.org/10.1038/nn.4266 pmid: 26950004
72 TJ Stachniak, A Ghosh, SM Sternson. Chemogenetic synaptic silencing of neural circuits localizes a hypothalamus→midbrain pathway for feeding behavior. Neuron 2014; 82( 4): 797– 808
https://doi.org/10.1016/j.neuron.2014.04.008 pmid: 24768300
73 E Vardy, JE Robinson, C Li, RHJ Olsen, JF DiBerto, PM Giguere, FM Sassano, XP Huang, H Zhu, DJ Urban, KL White, JE Rittiner, NA Crowley, KE Pleil, CM Mazzone, PD Mosier, J Song, TL Kash, CJ Malanga, MJ Krashes, BL Roth. A new DREADD facilitates the multiplexed chemogenetic interrogation of behavior. Neuron 2015; 86( 4): 936– 946
https://doi.org/10.1016/j.neuron.2015.03.065 pmid: 25937170
74 TM Preuss, SP Wise. Evolution of prefrontal cortex. Neuropsychopharmacology 2022; 47( 1): 3– 19
https://doi.org/10.1038/s41386-021-01076-5 pmid: 34363014
75 DJ Schaeffer, Y Hori, KM Gilbert, JS Gati, RS Menon, S Everling. Divergence of rodent and primate medial frontal cortex functional connectivity. Proc Natl Acad Sci USA 2020; 117( 35): 21681– 21689
https://doi.org/10.1073/pnas.2003181117 pmid: 32817555
76 AC Roberts. Prefrontal regulation of threat-elicited behaviors: a pathway to translation. Annu Rev Psychol 2020; 71( 1): 357– 387
https://doi.org/10.1146/annurev-psych-010419-050905 pmid: 31622562
77 CA Heidbreder, HJ Groenewegen. The medial prefrontal cortex in the rat: evidence for a dorso-ventral distinction based upon functional and anatomical characteristics. Neurosci Biobehav Rev 2003; 27( 6): 555– 579
https://doi.org/10.1016/j.neubiorev.2003.09.003 pmid: 14599436
78 DM Warthen, PS Lambeth, M Ottolini, Y Shi, BS Barker, RP Gaykema, BA Newmyer, J Joy-Gaba, Y Ohmura, E Perez-Reyes, AD Güler, MK Patel, MM Scott. Activation of pyramidal neurons in mouse medial prefrontal cortex enhances food-seeking behavior while reducing impulsivity in the absence of an effect on food intake. Front Behav Neurosci 2016; 10 : 63
https://doi.org/10.3389/fnbeh.2016.00063 pmid: 27065827
79 HE 3rd Covington, MK Lobo, I Maze, V Vialou, JM Hyman, S Zaman, Q LaPlant, E Mouzon, S Ghose, CA Tamminga, RL Neve, K Deisseroth, EJ Nestler. Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 2010; 30( 48): 16082– 16090
https://doi.org/10.1523/JNEUROSCI.1731-10.2010 pmid: 21123555
80 YH Chen, JL Wu, NY Hu, JP Zhuang, WP Li, SR Zhang, XW Li, JM Yang, TM Gao. Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear. J Clin Invest 2021; 131( 14): e145692
https://doi.org/10.1172/JCI145692 pmid: 34263737
81 GQ Wang, C Cen, C Li, S Cao, N Wang, Z Zhou, XM Liu, Y Xu, NX Tian, Y Zhang, J Wang, LP Wang, Y Wang. Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety. Nat Commun 2015; 6( 1): 7660
https://doi.org/10.1038/ncomms8660 pmid: 26179626
82 A Adhikari, TN Lerner, J Finkelstein, S Pak, JH Jennings, TJ Davidson, E Ferenczi, LA Gunaydin, JJ Mirzabekov, L Ye, SY Kim, A Lei, K Deisseroth. Basomedial amygdala mediates top-down control of anxiety and fear. Nature 2015; 527( 7577): 179– 185
https://doi.org/10.1038/nature15698 pmid: 26536109
83 BD Hare, R Shinohara, RJ Liu, S Pothula, RJ DiLeone, RS Duman. Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nat Commun 2019; 10( 1): 223
https://doi.org/10.1038/s41467-018-08168-9 pmid: 30644390
84 S Gee, I Ellwood, T Patel, F Luongo, K Deisseroth, VS Sohal. Synaptic activity unmasks dopamine D2 receptor modulation of a specific class of layer V pyramidal neurons in prefrontal cortex. J Neurosci 2012; 32( 14): 4959– 4971
https://doi.org/10.1523/JNEUROSCI.5835-11.2012 pmid: 22492051
85 M Fuchikami, A Thomas, R Liu, ES Wohleb, BB Land, RJ DiLeone, GK Aghajanian, RS Duman. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proc Natl Acad Sci USA 2015; 112( 26): 8106– 8111
https://doi.org/10.1073/pnas.1414728112 pmid: 26056286
86 BA Vogt, G Paxinos. Cytoarchitecture of mouse and rat cingulate cortex with human homologies. Brain Struct Funct 2014; 219( 1): 185– 192
https://doi.org/10.1007/s00429-012-0493-3 pmid: 23229151
87 SR Heilbronner, J Rodriguez-Romaguera, GJ Quirk, HJ Groenewegen, SN Haber. Circuit-based corticostriatal homologies between rat and primate. Biol Psychiatry 2016; 80( 7): 509– 521
https://doi.org/10.1016/j.biopsych.2016.05.012 pmid: 27450032
88 L Alexander, CM Wood, PLR Gaskin, SJ Sawiak, TD Fryer, YT Hong, L McIver, HF Clarke, AC Roberts. Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat. Nat Commun 2020; 11( 1): 5386
https://doi.org/10.1038/s41467-020-19167-0 pmid: 33106488
89 J Jhang, H Lee, MS Kang, HS Lee, H Park, JH Han. Anterior cingulate cortex and its input to the basolateral amygdala control innate fear response. Nat Commun 2018; 9( 1): 2744
https://doi.org/10.1038/s41467-018-05090-y pmid: 30013065
90 LL Falconi-Sobrinho, T Dos Anjos-Garcia, NC Coimbra. Nitric oxide-mediated defensive and antinociceptive responses organised at the anterior hypothalamus of mice are modulated by glutamatergic inputs from area 24b of the cingulate cortex. J Psychopharmacol 2021; 35( 1): 78– 90
https://doi.org/10.1177/0269881120967881 pmid: 33300404
91 LL Falconi-Sobrinho T Dos Anjos-Garcia DH Elias-Filho NC Coimbra. Unravelling cortico-hypothalamic pathways regulating unconditioned fear-induced antinociception and defensive behaviours. Neuropharmacology 2017; 113(Pt A): 367–385 doi:10.1016/j.neuropharm.2016.10.001
pmid: 27717879
92 LL Falconi-Sobrinho, T Dos Anjos-Garcia, R de Oliveira, NC Coimbra. Decrease in NMDA receptor-signalling activity in the anterior cingulate cortex diminishes defensive behaviour and unconditioned fear-induced antinociception elicited by GABAergic tonic inhibition impairment in the posterior hypothalamus. Eur Neuropsychopharmacol 2017; 27( 11): 1120– 1131
https://doi.org/10.1016/j.euroneuro.2017.09.002 pmid: 28939165
93 CE Page, R Shepard, K Heslin, L Coutellier. Prefrontal parvalbumin cells are sensitive to stress and mediate anxiety-related behaviors in female mice. Sci Rep 2019; 9( 1): 19772
https://doi.org/10.1038/s41598-019-56424-9 pmid: 31875035
94 A Soumier, E Sibille. Opposing effects of acute versus chronic blockade of frontal cortex somatostatin-positive inhibitory neurons on behavioral emotionality in mice. Neuropsychopharmacology 2014; 39( 9): 2252– 2262
https://doi.org/10.1038/npp.2014.76 pmid: 24690741
95 DP Tromp, DW Grupe, DJ Oathes, DR McFarlin, PJ Hernandez, TR Kral, JE Lee, M Adams, AL Alexander, JB Nitschke. Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Arch Gen Psychiatry 2012; 69( 9): 925– 934
https://doi.org/10.1001/archgenpsychiatry.2011.2178 pmid: 22945621
96 KE Prater, A Hosanagar, H Klumpp, M Angstadt, KL Phan. Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depress Anxiety 2013; 30( 3): 234– 241
https://doi.org/10.1002/da.22014 pmid: 23184639
97 JA Rosenkranz, AA Grace. Dopamine attenuates prefrontal cortical suppression of sensory inputs to the basolateral amygdala of rats. J Neurosci 2001; 21( 11): 4090– 4103
https://doi.org/10.1523/JNEUROSCI.21-11-04090.2001 pmid: 11356897
98 JC Motzkin, CL Philippi, RC Wolf, MK Baskaya, M Koenigs. Ventromedial prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol Psychiatry 2015; 77( 3): 276– 284
https://doi.org/10.1016/j.biopsych.2014.02.014 pmid: 24673881
99 GJ Quirk, E Likhtik, JG Pelletier, D Paré. Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. J Neurosci 2003; 23( 25): 8800– 8807
https://doi.org/10.1523/JNEUROSCI.23-25-08800.2003 pmid: 14507980
100 JA Rosenkranz, H Moore, AA Grace. The prefrontal cortex regulates lateral amygdala neuronal plasticity and responses to previously conditioned stimuli. J Neurosci 2003; 23( 35): 11054– 11064
https://doi.org/10.1523/JNEUROSCI.23-35-11054.2003 pmid: 14657162
101 A Adhikari, MA Topiwala, JA Gordon. Single units in the medial prefrontal cortex with anxiety-related firing patterns are preferentially influenced by ventral hippocampal activity. Neuron 2011; 71( 5): 898– 910
https://doi.org/10.1016/j.neuron.2011.07.027 pmid: 21903082
102 A Adhikari, MA Topiwala, JA Gordon. Synchronized activity between the ventral hippocampus and the medial prefrontal cortex during anxiety. Neuron 2010; 65( 2): 257– 269
https://doi.org/10.1016/j.neuron.2009.12.002 pmid: 20152131
103 WH Zhang, JY Zhang, A Holmes, BX Pan. Amygdala circuit substrates for stress adaptation and adversity. Biol Psychiatry 2021; 89( 9): 847– 856
https://doi.org/10.1016/j.biopsych.2020.12.026 pmid: 33691931
104 WZ Liu, WH Zhang, ZH Zheng, JX Zou, XX Liu, SH Huang, WJ You, Y He, JY Zhang, XD Wang, BX Pan. Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety. Nat Commun 2020; 11( 1): 2221
https://doi.org/10.1038/s41467-020-15920-7 pmid: 32376858
105 GM Parfitt, R Nguyen, JY Bang, AJ Aqrabawi, MM Tran, DK Seo, BA Richards, JC Kim. Bidirectional control of anxiety-related behaviors in mice: role of inputs arising from the ventral hippocampus to the lateral septum and medial prefrontal cortex. Neuropsychopharmacology 2017; 42( 8): 1715– 1728
https://doi.org/10.1038/npp.2017.56 pmid: 28294135
106 N Padilla-Coreano, SS Bolkan, GM Pierce, DR Blackman, WD Hardin, AL Garcia-Garcia, TJ Spellman, JA Gordon. Direct ventral hippocampal-prefrontal input is required for anxiety-related neural activity and behavior. Neuron 2016; 89( 4): 857– 866
https://doi.org/10.1016/j.neuron.2016.01.011 pmid: 26853301
107 A Kepecs, G Fishell. Interneuron cell types are fit to function. Nature 2014; 505( 7483): 318– 326
https://doi.org/10.1038/nature12983 pmid: 24429630
108 R Hattori, KV Kuchibhotla, RC Froemke, T Komiyama. Functions and dysfunctions of neocortical inhibitory neuron subtypes. Nat Neurosci 2017; 20( 9): 1199– 1208
https://doi.org/10.1038/nn.4619 pmid: 28849791
109 B Wamsley, G Fishell. Genetic and activity-dependent mechanisms underlying interneuron diversity. Nat Rev Neurosci 2017; 18( 5): 299– 309
https://doi.org/10.1038/nrn.2017.30 pmid: 28381833
110 BA Seybold, A Stanco, KK Cho, GB Potter, C Kim, VS Sohal, JL Rubenstein, CE Schreiner. Chronic reduction in inhibition reduces receptive field size in mouse auditory cortex. Proc Natl Acad Sci USA 2012; 109( 34): 13829– 13834
https://doi.org/10.1073/pnas.1205909109 pmid: 22753490
111 AC Felix-Ortiz, A Burgos-Robles, ND Bhagat, CA Leppla, KM Tye. Bidirectional modulation of anxiety-related and social behaviors by amygdala projections to the medial prefrontal cortex. Neuroscience 2016; 321 : 197– 209
https://doi.org/10.1016/j.neuroscience.2015.07.041 pmid: 26204817
112 FH Do-Monte, K Quiñones-Laracuente, GJ Quirk. A temporal shift in the circuits mediating retrieval of fear memory. Nature 2015; 519( 7544): 460– 463
https://doi.org/10.1038/nature14030 pmid: 25600268
113 CU Wallis, RN Cardinal, L Alexander, AC Roberts, HF Clarke. Opposing roles of primate areas 25 and 32 and their putative rodent homologs in the regulation of negative emotion. Proc Natl Acad Sci USA 2017; 114( 20): E4075– E4084
https://doi.org/10.1073/pnas.1620115114 pmid: 28461477
114 HS Kim, HY Cho, GJ Augustine, JH Han. Selective control of fear expression by optogenetic manipulation of infralimbic cortex after extinction. Neuropsychopharmacology 2016; 41( 5): 1261– 1273
https://doi.org/10.1038/npp.2015.276 pmid: 26354044
115 LA DeNardo, CD Liu, WE Allen, EL Adams, D Friedmann, L Fu, CJ Guenthner, M Tessier-Lavigne, L Luo. Temporal evolution of cortical ensembles promoting remote memory retrieval. Nat Neurosci 2019; 22( 3): 460– 469
https://doi.org/10.1038/s41593-018-0318-7 pmid: 30692687
116 KR Ramanathan, J Jin, TF Giustino, MR Payne, S Maren. Prefrontal projections to the thalamic nucleus reuniens mediate fear extinction. Nat Commun 2018; 9( 1): 4527
https://doi.org/10.1038/s41467-018-06970-z pmid: 30375397
117 DW Bloodgood, JA Sugam, A Holmes, TL Kash. Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Transl Psychiatry 2018; 8( 1): 60
https://doi.org/10.1038/s41398-018-0106-x pmid: 29507292
118 FH Do-Monte, G Manzano-Nieves, K Quiñones-Laracuente, L Ramos-Medina, GJ Quirk. Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 2015; 35( 8): 3607– 3615
https://doi.org/10.1523/JNEUROSCI.3137-14.2015 pmid: 25716859
119 MR Milad, GJ Quirk. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 2002; 420( 6911): 70– 74
https://doi.org/10.1038/nature01138 pmid: 12422216
120 MR Milad, GJ Quirk. Fear extinction as a model for translational neuroscience: ten years of progress. Annu Rev Psychol 2012; 63( 1): 129– 151
https://doi.org/10.1146/annurev.psych.121208.131631 pmid: 22129456
121 MR Milad, SL Rauch, RK Pitman, GJ Quirk. Fear extinction in rats: implications for human brain imaging and anxiety disorders. Biol Psychol 2006; 73( 1): 61– 71
https://doi.org/10.1016/j.biopsycho.2006.01.008 pmid: 16476517
122 MR Milad, CI Wright, SP Orr, RK Pitman, GJ Quirk, SL Rauch. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry 2007; 62( 5): 446– 454
https://doi.org/10.1016/j.biopsych.2006.10.011 pmid: 17217927
123 EA Phelps, MR Delgado, KI Nearing, JE LeDoux. Extinction learning in humans: role of the amygdala and vmPFC. Neuron 2004; 43( 6): 897– 905
https://doi.org/10.1016/j.neuron.2004.08.042 pmid: 15363399
124 CH Chang, S Maren. Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats. Behav Neurosci 2010; 124( 3): 391– 397
https://doi.org/10.1037/a0019479 pmid: 20528083
125 P Rajasethupathy, S Sankaran, JH Marshel, CK Kim, E Ferenczi, SY Lee, A Berndt, C Ramakrishnan, A Jaffe, M Lo, C Liston, K Deisseroth. Projections from neocortex mediate top-down control of memory retrieval. Nature 2015; 526( 7575): 653– 659
https://doi.org/10.1038/nature15389 pmid: 26436451
126 R Marek, L Xu, RKP Sullivan, P Sah. Excitatory connections between the prelimbic and infralimbic medial prefrontal cortex show a role for the prelimbic cortex in fear extinction. Nat Neurosci 2018; 21( 5): 654– 658
https://doi.org/10.1038/s41593-018-0137-x pmid: 29686260
127 KA Cummings, RL Clem. Prefrontal somatostatin interneurons encode fear memory. Nat Neurosci 2020; 23( 1): 61– 74
https://doi.org/10.1038/s41593-019-0552-7 pmid: 31844314
128 A Mukherjee, P Caroni. Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity. Nat Commun 2018; 9( 1): 2727
https://doi.org/10.1038/s41467-018-05318-x pmid: 30006525
129 YH Chen, NY Hu, DY Wu, LL Bi, ZY Luo, L Huang, JL Wu, ML Wang, JT Li, YL Song, SR Zhang, W Jie, XW Li, SZ Zhang, JM Yang, TM Gao. PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction. Mol Psychiatry 2022; 27( 2): 896– 906
https://doi.org/10.1038/s41380-021-01355-z pmid: 34697452
130 N Karalis, C Dejean, F Chaudun, S Khoder, RR Rozeske, H Wurtz, S Bagur, K Benchenane, A Sirota, J Courtin, C Herry. 4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior. Nat Neurosci 2016; 19( 4): 605– 612
https://doi.org/10.1038/nn.4251 pmid: 26878674
131 J Courtin, F Chaudun, RR Rozeske, N Karalis, C Gonzalez-Campo, H Wurtz, A Abdi, J Baufreton, TC Bienvenu, C Herry. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression. Nature 2014; 505( 7481): 92– 96
https://doi.org/10.1038/nature12755 pmid: 24256726
132 O Bukalo, CR Pinard, S Silverstein, C Brehm, ND Hartley, N Whittle, G Colacicco, E Busch, S Patel, N Singewald, A Holmes. Prefrontal inputs to the amygdala instruct fear extinction memory formation. Sci Adv 2015; 1( 6): e1500251
https://doi.org/10.1126/sciadv.1500251 pmid: 26504902
133 W Xu, TC Südhof. A neural circuit for memory specificity and generalization. Science 2013; 339( 6125): 1290– 1295
https://doi.org/10.1126/science.1229534 pmid: 23493706
134 FG Davoodi, F Motamedi, E Akbari, E Ghanbarian, B Jila. Effect of reversible inactivation of reuniens nucleus on memory processing in passive avoidance task. Behav Brain Res 2011; 221( 1): 1– 6
https://doi.org/10.1016/j.bbr.2011.02.020 pmid: 21354215
135 HT Ito, SJ Zhang, MP Witter, EI Moser, MB Moser. A prefrontal-thalamo-hippocampal circuit for goal-directed spatial navigation. Nature 2015; 522( 7554): 50– 55
https://doi.org/10.1038/nature14396 pmid: 26017312
136 RP Vertes, WB Hoover, K Szigeti-Buck, C Leranth. Nucleus reuniens of the midline thalamus: link between the medial prefrontal cortex and the hippocampus. Brain Res Bull 2007; 71( 6): 601– 609
https://doi.org/10.1016/j.brainresbull.2006.12.002 pmid: 17292803
137 AL Griffin. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory. Front Syst Neurosci 2015; 9 : 29
https://doi.org/10.3389/fnsys.2015.00029 pmid: 25805977
138 WB Hoover, RP Vertes. Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 2007; 212( 2): 149– 179
https://doi.org/10.1007/s00429-007-0150-4 pmid: 17717690
139 G Ji, V Neugebauer. Modulation of medial prefrontal cortical activity using in vivo recordings and optogenetics. Mol Brain 2012; 5( 1): 36
https://doi.org/10.1186/1756-6606-5-36 pmid: 23044043
140 KI van Aerde, TS Heistek, HD Mansvelder. Prelimbic and infralimbic prefrontal cortex interact during fast network oscillations. PLoS One 2008; 3( 7): e2725
https://doi.org/10.1371/journal.pone.0002725 pmid: 18628964
141 V Senn, SB Wolff, C Herry, F Grenier, I Ehrlich, J Gründemann, JP Fadok, C Müller, JJ Letzkus, A Lüthi. Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 2014; 81( 2): 428– 437
https://doi.org/10.1016/j.neuron.2013.11.006 pmid: 24462103
142 O Klavir, M Prigge, A Sarel, R Paz, O Yizhar. Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex. Nat Neurosci 2017; 20( 6): 836– 844
https://doi.org/10.1038/nn.4523 pmid: 28288126
143 MA Parent, L Wang, J Su, T Netoff, LL Yuan. Identification of the hippocampal input to medial prefrontal cortex in vitro. Cereb Cortex 2010; 20( 2): 393– 403
https://doi.org/10.1093/cercor/bhp108 pmid: 19515741
144 R Marek, J Jin, TD Goode, TF Giustino, Q Wang, GM Acca, R Holehonnur, JE Ploski, PJ Fitzgerald, T Lynagh, JW Lynch, S Maren, P Sah. Hippocampus-driven feed-forward inhibition of the prefrontal cortex mediates relapse of extinguished fear. Nat Neurosci 2018; 21( 3): 384– 392
https://doi.org/10.1038/s41593-018-0073-9 pmid: 29403033
145 HJ Pi, B Hangya, D Kvitsiani, JI Sanders, ZJ Huang, A Kepecs. Cortical interneurons that specialize in disinhibitory control. Nature 2013; 503( 7477): 521– 524
https://doi.org/10.1038/nature12676 pmid: 24097352
146 RC Froemke, MM Merzenich, CE Schreiner. A synaptic memory trace for cortical receptive field plasticity. Nature 2007; 450( 7168): 425– 429
https://doi.org/10.1038/nature06289 pmid: 18004384
147 S Royer, BV Zemelman, A Losonczy, J Kim, F Chance, JC Magee, G Buzsáki. Control of timing, rate and bursts of hippocampal place cells by dendritic and somatic inhibition. Nat Neurosci 2012; 15( 5): 769– 775
https://doi.org/10.1038/nn.3077 pmid: 22446878
148 AC Butler, JE Chapman, EM Forman, AT Beck. The empirical status of cognitive-behavioral therapy: a review of meta-analyses. Clin Psychol Rev 2006; 26( 1): 17– 31
https://doi.org/10.1016/j.cpr.2005.07.003 pmid: 16199119
149 Q Sun, X Li, M Ren, M Zhao, Q Zhong, Y Ren, P Luo, H Ni, X Zhang, C Zhang, J Yuan, A Li, M Luo, H Gong, Q Luo. A whole-brain map of long-range inputs to GABAergic interneurons in the mouse medial prefrontal cortex. Nat Neurosci 2019; 22( 8): 1357– 1370
https://doi.org/10.1038/s41593-019-0429-9 pmid: 31285615
150 S Ährlund-Richter, Y Xuan, Lunteren JA van, H Kim, C Ortiz, Dorocic I Pollak, K Meletis, M Carlén. A whole-brain atlas of monosynaptic input targeting four different cell types in the medial prefrontal cortex of the mouse. Nat Neurosci 2019; 22( 4): 657– 668
https://doi.org/10.1038/s41593-019-0354-y pmid: 30886408
151 MR Delgado, JS Beer, LK Fellows, SA Huettel, ML Platt, GJ Quirk, D Schiller. Viewpoints: Dialogues on the functional role of the ventromedial prefrontal cortex. Nat Neurosci 2016; 19( 12): 1545– 1552
https://doi.org/10.1038/nn.4438 pmid: 27898086
152 C Dejean, J Courtin, RR Rozeske, MC Bonnet, V Dousset, T Michelet, C Herry. Neuronal circuits for fear expression and recovery: recent advances and potential therapeutic strategies. Biol Psychiatry 2015; 78( 5): 298– 306
https://doi.org/10.1016/j.biopsych.2015.03.017 pmid: 25908496
153 JH Cho, K Deisseroth, VY Bolshakov. Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron 2013; 80( 6): 1491– 1507
https://doi.org/10.1016/j.neuron.2013.09.025 pmid: 24290204
154 N Kulesskaya, V Voikar. Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure. Physiol Behav 2014; 133 : 30– 38
https://doi.org/10.1016/j.physbeh.2014.05.006 pmid: 24832050
155 CN Snyder, AR Brown, D Buffalari. Similar tests of anxiety-like behavior yield different results: comparison of the open field and free exploratory rodent procedures. Physiol Behav 2021; 230 : 113246
https://doi.org/10.1016/j.physbeh.2020.113246 pmid: 33189728
156 AB Wiltschko, T Tsukahara, A Zeine, R Anyoha, WF Gillis, JE Markowitz, RE Peterson, J Katon, MJ Johnson, SR Datta. Revealing the structure of pharmacobehavioral space through motion sequencing. Nat Neurosci 2020; 23( 11): 1433– 1443
https://doi.org/10.1038/s41593-020-00706-3 pmid: 32958923
157 L von Ziegler, O Sturman, J Bohacek. Big behavior: challenges and opportunities in a new era of deep behavior profiling. Neuropsychopharmacology 2021; 46( 1): 33– 44
https://doi.org/10.1038/s41386-020-0751-7 pmid: 32599604
158 N Liu, Y Han, H Ding, K Huang, P Wei, L Wang. Objective and comprehensive re-evaluation of anxiety-like behaviors in mice using the Behavior Atlas. Biochem Biophys Res Commun 2021; 559 : 1– 7
https://doi.org/10.1016/j.bbrc.2021.03.125 pmid: 33932895
[1] Xiao He, Chentao Jin, Mindi Ma, Rui Zhou, Shuang Wu, Haoying Huang, Yuting Li, Qiaozhen Chen, Mingrong Zhang, Hong Zhang, Mei Tian. PET imaging on neurofunctional changes after optogenetic stimulation in a rat model of panic disorder[J]. Front. Med., 2019, 13(5): 602-609.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed