In addition to modulating a number of cognitive functions including reward, punishment, motivation, and salience, dopamine (DA) plays a pivotal role in regulating threat-related emotional memory. Changes in neural circuits of the amygdala nuclei are also critically involved in the acquisition and expression of emotional memory. In this review, we summarize the regulation of amygdala circuits by DA. Specifically, we describe DA signaling in the amygdala, and DA regulation of synaptic transmission and synaptic plasticity of the amygdala neurons. Finally, we discuss a potential contribution of DA-related mechanisms to the pathogenesis of posttraumatic stress disorder.
AsedeDBoschDLüthiAFerragutiFEhrlichI.2015. Sensory inputs to intercalated cells provide fear-learning modulated inhibition to the basolateral amygdala. Neuron86:541–54.
2.
BeierKTSteinbergEEDeLoachKEXieSMiyamichiKSchwarzL, and others. 2015. Circuit architecture of VTA dopamine neurons revealed by systematic input-output mapping. Cell162:622–34.
3.
BissièreSHumeauYLüthiA.2003. Dopamine gates LTP induction in lateral amygdala by suppressing feedforward inhibition. Nat Neurosci6:587–92.
4.
BrischouxFChakrabortySBrierleyDIUnglessMA. 2009. Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci U S A106:4894–9.
5.
Bromberg-MartinESMatsumotoMHikosakaO.2010. Dopamine in motivational control: rewarding, aversive, and alerting. Neuron68:815–34.
6.
BullDRBakhtiarRSheehanMJ. 1991. Characterization of dopamine autoreceptors in the amygdala: A fast cyclic voltammetric study in vitro. Neurosci Lett134:41–4.
7.
ChuHYItoWLiJMorozovA.2012. Target-specific suppression of GABA release from parvalbumin interneurons in the basolateral amygdala by dopamine. J Neurosci32:14815–20.
8.
de OliveiraARReimerAEde MacedoCEde CarvalhoMCSilvaMABrandãoML. 2011. Conditioned fear is modulated by D2 receptor pathway connecting the ventral tegmental area and basolateral amygdala. Neurobiol Learn Mem95:37–45.
9.
de Souza CaetanoKAde OliveiraARBrandãoML. 2013. Dopamine D2 receptors modulate the expression of contextual conditioned fear: role of the ventral tegmental area and the basolateral amygdala. Behav Pharmacol24:264–74.
10.
DiazMRChappellAMChristianDTAndersonNJMcCoolBA. 2011. Dopamine D3-like receptors modulate anxiety-like behavior and regulate GABAergic transmission in the rat lateral/basolateral amygdala. Neuropsychopharmacology36:1090–103.
11.
EhrlichIHumeauYGrenierFCiocchiSHerryCLüthiA.2009. Amygdala inhibitory circuits and the control of fear memory. Neuron62:757–71.
12.
FadokJPDickersonTMPalmiterRD. 2009. Dopamine is necessary for cue-dependent fear conditioning. J Neurosci29:11089–97.
13.
FiorenzaNGRosaJIzquierdoIMyskiwJC. 2012. Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas. Behav Brain Res232:210–6.
14.
FiorilloCD. 2013. Two dimensions of value: dopamine neurons represent reward but not aversiveness. Science341:546–9.
15.
FiorilloCDSongMRYunSR. 2013. Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli. J Neurosci33:4710–25.
16.
FordCPMarkGPWilliamsJT. 2006. Properties and opioid inhibition of mesolimbic dopamine neurons vary according to target location. J Neurosci26:2788–97.
17.
FremeauRTJrDuncanGEFornarettoMGDearryAGingrichJABreeseGR, and others. 1991. Localization of D1 dopamine receptor mRNA in brain supports a role in cognitive, affective, and neuroendocrine aspects of dopaminergic neurotransmission. Proc Natl Acad Sci U S A88:3772–6.
18.
FuxeKJacobsenKXHöistadMTinnerBJanssonAStainesWA, and others. 2003. The dopamine D1 receptor-rich main and paracapsular intercalated nerve cell groups of the rat amygdala: relationship to the dopamine innervation. Neuroscience119:733–46.
19.
GeracitanoRKaufmannWASzaboGFerragutiFCapognaM.2007. Synaptic heterogeneity between mouse paracapsular intercalated neurons of the amygdala. J Physiol585:117–34.
20.
GoreBBSodenMEZweifelLS. 2014. Visualization of plasticity in fear-evoked calcium signals in midbrain dopamine neurons. Learn Mem21:575–9.
21.
GrebaQGifkinsAKokkinidisL.2001. Inhibition of amygdaloid dopamine D2 receptors impairs emotional learning measured with fear-potentiated startle. Brain Res899:218–26.
22.
GriffinGDCharronDAl-DaccakR.2014. Post-traumatic stress disorder: revisiting adrenergics, glucocorticoids, immune system effects and homeostasis. Clin Transl Immunology3:e27.
23.
GuarraciFAFrohardtRJKappBS. 1999. Amygdaloid D1 dopamine receptor involvement in Pavlovian fear conditioning. Brain Res827:28–40.
24.
GuarraciFAFrohardtRJFallsWAKappBS. 2000. The effects of intra-amygdaloid infusions of a D2 dopamine receptor antagonist on Pavlovian fear conditioning. Behav Neurosci114:647–51.
25.
HaubensakWKunwarPSCaiHCiocchiSWallNRPonnusamyR, and others. 2010. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature468:270–6.
26.
HeathFCJurkusRBastTPezzeMALeeJLVoigtJP, and others. 2015. Dopamine D1-like receptor signalling in the hippocampus and amygdala modulates the acquisition of contextual fear conditioning. Psychopharmacology232:2619–29.
27.
HikindNMarounM.2008. Microinfusion of the D1 receptor antagonist, SCH23390 into the IL but not the BLA impairs consolidation of extinction of auditory fear conditioning. Neurobiol Learn Mem90:217–22.
28.
HuangYYKandelER. 2007. Low-frequency stimulation induces a pathway-specific late phase of LTP in the amygdala that is mediated by PKA and dependent on protein synthesis. Learn Mem14:497–503.
29.
HübnerCBoschDGallALüthiAEhrlichI.2014. Ex vivo dissection of optogenetically activated mPFC and hippocampal inputs to neurons in the basolateral amygdala: implications for fear and emotional memory. Front Behav Neurosci8:64.
30.
InglisFMMoghaddamB.1999. Dopaminergic innervation of the amygdala is highly responsive to stress. J Neurochem72:1088–94.
31.
JonesGLSodenMEKnakalCRLeeHChungASMerriamEB, and others. 2015. A genetic link between discriminative fear coding by the lateral amygdala, dopamine, and fear generalization. Elife4:e08969.
32.
KaouaneNPorteYValléeMBrayda-BrunoLMonsNCalandreauL, and others. 2012. Glucocorticoids can induce PTSD-like memory impairments in mice. Science335:1510–3.
33.
KimJKwonJTKimHSJosselynSAHanJH. 2014. Memory recall and modifications by activating neurons with elevated CREB. Nat Neurosci17:65–72.
34.
KrönerSRosenkranzJAGraceAABarrionuevoG.2005. Dopamine modulates excitability of basolateral amygdala neurons in vitro. J Neurophysiol93:1598–610.
35.
KwonOBLeeJHKimHJLeeSLeeSJeongMJ, and others. 2015. Dopamine regulation of amygdala inhibitory circuits for expression of learned fear. Neuron88:378–89.
36.
LammelSHetzelAHäckelOJonesILissBRoeperJ.2008. Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic dopamine system. Neuron57:760–73.
37.
LamontEWKokkinidisL.1998. Infusion of the dopamine D1 receptor antagonist SCH 23390 into the amygdala blocks fear expression in a potentiated startle paradigm. Brain Res795:128–36.
38.
LandBBNarayananNSLiuRJGianessiCABraytonCEGrimaldiDM, and others. 2014. Medial prefrontal D1 dopamine neurons control food intake. Nat Neurosci17:248–53.
39.
LebowMNeufeld-CohenAKupermanYTsooryMGilSChenA.2012. Susceptibility to PTSD-like behavior is mediated by corticotropin-releasing factor receptor type 2 levels in the bed nucleus of the stria terminalis. J Neurosci32:6906–16.
40.
LeDouxJE. 2000. Emotion circuits in the brain. Annu Rev Neurosci23:155–84.
41.
LeeSKimSJKwonOBLeeJHKimJH. 2013. Inhibitory networks of the amygdala for emotional memory. Front Neural Circuits7:129.
42.
LiCDabrowskaJHazraRRainnieDG. 2011. Synergistic activation of dopamine D1 and TrkB receptors mediate gain control of synaptic plasticity in the basolateral amygdala. PLoS One6:e26065.
43.
LiHPenzoMATaniguchiHKopecCDHuangZJLiB.2013. Experience-dependent modification of a central amygdala fear circuit. Nat Neurosci16:332–9.
44.
LikhtikEPelletierJGPazRParéD.2005. Prefrontal control of the amygdala. J Neurosci25:7429–37.
45.
LorétanKBissièreSLüthiA.2004. Dopaminergic modulation of spontaneous inhibitory network activity in the lateral amygdala. Neuropharmacology47:631–9.
46.
LucasEKJegarlAMMorishitaHClemRL. 2016. Multimodal and site-specific plasticity of amygdala parvalbumin interneurons after fear learning. Neuron91:629–43.
47.
LüthiALüscherC.2014. Pathological circuit function underlying addiction and anxiety disorders. Nat Neurosci17:1635–43.
48.
MaltaisSCôtéSDroletGFalardeauP.2000. Cellular colocalization of dopamine D1 mRNA and D2 receptor in rat brain using a D2 dopamine receptor specific polyclonal antibody. Prog Neuropsychopharmacol Biol Psychiatry24:1127–49.
49.
MańkoMGeracitanoRCapognaM.2011. Functional connectivity of the main intercalated nucleus of the mouse amygdala. J Physiol589:1911–25.
50.
MargolisEBLockHCheferVIShippenbergTSHjelmstadGOFieldsHL. 2006. Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. Proc Natl Acad Sci U S A103:2938–42.
MarowskyAYanagawaYObataKVogtKE. 2005. A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron48:1025–37.
53.
MenegasWBerganJFOgawaSKIsogaiYUmadevi VenkatarajuKOstenP, and others. 2015. Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass. Elife4:e10032.
54.
MingoteSChuhmaNKusnoorSVFieldBDeutchAYRayportS.2015. Functional connectome analysis of dopamine neuron glutamatergic connections in forebrain regions. J Neurosci35:16259–71.
55.
MullerJFMascagniFMcDonaldAJ. 2009. Dopaminergic innervation of pyramidal cells in the rat basolateral amygdala. Brain Struct Funct213:275–88.
56.
NabaviSFoxRProulxCDLinJYTsienRYMalinowR.2014. Engineering a memory with LTD and LTP. Nature511:348–52.
57.
NaderKLeDouxJ.1999. Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations. Behav Neurosci113:891–901.
58.
NieZZorrillaEPMadambaSGRiceKCRobertoMSigginsGR. 2009. Presynaptic CRF1 receptors mediate the ethanol enhancement of GABAergic transmission in the mouse central amygdala. ScientificWorldJournal9:68–8.
59.
OeiTPKingMG. 1980. Catecholamines and aversive learning: a review. Neurosci Biobehav Rev4:161–73.
60.
PapeHCPareD.2010. Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev90:419–63.
61.
PareDDuvarciS.2012. Amygdala microcircuits mediating fear expression and extinction. Curr Opin Neurobiol22:717–23.
62.
PignatelliMBonciA.2015. Role of dopamine neurons in reward and aversion: a synaptic plasticity perspective. Neuron86:1145–57.
63.
PinardCRMullerJFMascagniFMcDonaldAJ. 2008. Dopaminergic innervation of interneurons in the rat basolateral amygdala. Neuroscience157:850–63.
64.
ReznikovRBinkoMNobregaJNHamaniC.2016. Deep brain stimulation in animal models of fear, anxiety, and posttraumatic stress disorder. Neuropsychopharmacology41:2810–17.
65.
RoganMTStäubliUVLeDouxJE. 1997. Fear conditioning induces associative long-term potentiation in the amygdala. Nature390:604–7.
66.
RosenkranzJAGraceAA. 1999. Modulation of basolateral amygdala neuronal firing and afferent drive by dopamine receptor activation in vivo. J Neurosci19:11027–39.
67.
RosenkranzJAGraceAA. 2001. Dopamine attenuates prefrontal cortical suppression of sensory inputs to the basolateral amygdala of rats. J Neurosci21:4090–103.
68.
SalamoneJDCorreaM.2012. The mysterious motivational functions of mesolimbic dopamine. Neuron76:470–85.
69.
ShinRMTsvetkovEBolshakovVY. 2006. Spatiotemporal asymmetry of associative synaptic plasticity in fear conditioning pathways. Neuron52:883–96.
70.
SilbermanYWinderDG. 2013. Corticotropin releasing factor and catecholamines enhance glutamatergic neurotransmission in the lateral subdivision of the central amygdala. Neuropharmacology70:316–23.
71.
StrobelCMarekRGoochHMSullivanRKSahP.2015. Prefrontal and auditory input to intercalated neurons of the amygdala. Cell Rep10:1435–42.
72.
SwansonLW. 1982. The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull9:321–53.
73.
TovotePFadokJPLüthiA.2015. Neuronal circuits for fear and anxiety. Nat Rev Neurosci16:317–31.
74.
ValentiOLodgeDJGraceAA. 2011. Aversive stimuli alter ventral tegmental area dopamine neuron activity via a common action in the ventral hippocampus. J Neurosci31:4280–9.
75.
WangDVTsienJZ. 2011. Convergent processing of both positive and negative motivational signals by the VTA dopamine neuronal populations. PLoS One6:e17047.
76.
WeinerDMLeveyAISunaharaRKNiznikHBO’DowdBFSeemanP, and others. 1991. D1 and D2 dopamine receptor mRNA in rat brain. Proc Natl Acad Sci U S A88:1859–63.
77.
WhitakerAMGilpinNWEdwardsS.2014. Animal models of post-traumatic stress disorder and recent neurobiological insights. Behav Pharmacol25:398–409.
78.
WolffSBGründemannJTovotePKrabbeSJacobsonGAMüllerC, and others. 2014. Amygdala interneuron subtypes control fear learning through disinhibition. Nature509:453–8.
79.
YehudaRGolierJAHalliganSLMeaneyMBiererLM. 2004. The ACTH response to dexamethasone in PTSD. Am J Psychiatry161:1397–403.
80.
YoungAMReesKR. 1998. Dopamine release in the amygdaloid complex of the rat, studied by brain microdialysis. Neurosci Lett249:49–52.
