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From circuits to behaviour in the amygdala

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Abstract

The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits.

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Figure 1: Evolution of the amygdala across species.
Figure 2: Number of studies on the amygdala.
Figure 3: Amygdalar circuits that are sufficient to alter behaviour in a diversity of domains.
Figure 4: Model of amygdala microcircuits that give rise to behaviour.
Figure 5: Interneuron and principal neuron interactions within the basolateral complex of the amygdala (BLA).

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References

  1. McDonald, A. J. Cortical pathways to the mammalian amygdala. Prog. Neurobiol. 55, 257–332 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Jarvis, E. D. et al. Avian brains and a new understanding of vertebrate brain evolution. Nature Rev. Neurosci. 6, 151–159 (2005).

    Article  CAS  Google Scholar 

  3. Johnston, J. B. Further contributions to the study of the evolution of the forebrain. J. Comp. Neurol. 35, 337–481 (1923).

    Article  Google Scholar 

  4. Kappers, C. U. A., Huber, G. C. & Crosby, E. C. The Comparative Anatomy of the Nervous System of Vertebrates, Including Man (Macmillan, 1936).

    Book  Google Scholar 

  5. Lanuza, E., Belekhova, M., Martínez-Marcos, A., Font, C. & Martínez-García, F. Identification of the reptilian basolateral amygdala: an anatomical investigation of the afferents to the posterior dorsal ventricular ridge of the lizard Podarcis hispanica. Eur. J. Neurosci. 10, 3517–3534 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Duvarci, S. & Pare, D. Amygdala microcircuits controlling learned fear. Neuron 82, 966–980 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Morrison, S. E. & Salzman, C. D. Re-valuing the amygdala. Curr. Opin. Neurobiol. 20, 221–230 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Murray, E. A. The amygdala, reward and emotion. Trends Cogn. Sci. 11, 489–497 (2007).

    Article  PubMed  Google Scholar 

  9. Stamatakis, A. M. et al. Amygdala and bed nucleus of the stria terminalis circuitry: implications for addiction-related behaviors. Neuropharmacology 76, 320–328 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Johansen, J. P., Cain, C. K., Ostroff, L. E. & LeDoux, J. E. Molecular mechanisms of fear learning and memory. Cell 147, 509–524 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pape, H.-C. & Pare, D. Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol. Rev. 90, 419–463 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Ehrlich, I. et al. Amygdala inhibitory circuits and the control of fear memory. Neuron 62, 757–771 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Brown, S. & Schäfer, E. An investigation into the functions of the occipital and temporal lobes of the monkey's brain. Phil. Trans. R. Soc. B 179, 303–327 (1888).

    ADS  Google Scholar 

  14. Klüver, H. & Bucy, P. 'Psychic blindness' and other symptoms following bilateral temporal lobectomy in Rhesus monkeys. Am. J. Physiol. 119, 352–353 (1937).

    Google Scholar 

  15. Weiskrantz, L. Behavioral changes associated with ablation of the amygdaloid complex in monkeys. J. Comp. Physiol. Psychol. 49, 381–391 (1956).

    Article  CAS  PubMed  Google Scholar 

  16. LeDoux, J. E., Cicchetti, P., Xagoraris, A. & Romanski, L. M. The lateral amygdaloid nucleus: sensory interface of the amygdala in fear conditioning. J. Neurosci. 10, 1062–1069 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Blanchard, D. C. & Blanchard, R. J. Innate and conditioned reactions to threat in rats with amygdaloid lesions. J. Comp. Physiol. Psychol. 81, 281–290 (1972).

    Article  CAS  PubMed  Google Scholar 

  18. Adolphs, R., Tranel, D., Damasio, H. & Damasio, A. Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature 372, 669–672 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Anderson, A. K. & Phelps, E. A. Lesions of the human amygdala impair enhanced perception of emotionally salient events. Nature 411, 305–309 (2001).

    Article  ADS  CAS  PubMed  Google Scholar 

  20. Marowsky, A., Yanagawa, Y., Obata, K. & Vogt, K. E. A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron 48, 1025–1037 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Freese, J. L. & Amaral, D. G. The organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey. J. Comp. Neurol. 486, 295–317 (2005).

    Article  PubMed  Google Scholar 

  22. Chareyron, L. J., Banta Lavenex, P., Amaral, D. G. & Lavenex, P. Stereological analysis of the rat and monkey amygdala. J. Comp. Neurol. 519, 3218–3239 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Corbit, L. H. & Balleine, B. W. Double dissociation of basolateral and central amygdala lesions on the general and outcome-specific forms of pavlovian-instrumental transfer. J. Neurosci. 25, 962–970 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Holland, P. C. & Gallagher, M. Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus-potentiated feeding and Pavlovian-instrumental transfer. Eur. J. Neurosci. 17, 1680–1694 (2003).

    Article  PubMed  Google Scholar 

  25. Quirk, G. J., Armony, J. L. & LeDoux, J. E. Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala. Neuron 19, 613–624 (1997).

    Article  CAS  PubMed  Google Scholar 

  26. Quirk, G. J., Repa, C. & LeDoux, J. E. Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat. Neuron 15, 1029–1039 (1995). This is a seminal study showing the increased responding of LA neurons to a CS after fear conditioning.

    Article  CAS  PubMed  Google Scholar 

  27. LaBar, K. S., Gatenby, J. C., Gore, J. C., LeDoux, J. E. & Phelps, E. A. Human amygdala activation during conditioned fear acquisition and extinction: a mixed-trial fMRI study. Neuron 20, 937–945 (1998).

    Article  CAS  PubMed  Google Scholar 

  28. Morris, J. S., Ohman, A. & Dolan, R. J. Conscious and unconscious emotional learning in the human amygdala. Nature 393, 467–470 (1998).

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Amano, T., Unal, C. T. & Paré, D. Synaptic correlates of fear extinction in the amygdala. Nature Neurosci. 13, 489–494 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Milad, M. R. & Quirk, G. J. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature 420, 70–74 (2002).

    Article  ADS  CAS  PubMed  Google Scholar 

  31. Phelps, E. A., Delgado, M. R., Nearing, K. I. & LeDoux, J. E. Extinction learning in humans: role of the amygdala and vmPFC. Neuron 43, 897–905 (2004).

    Article  CAS  PubMed  Google Scholar 

  32. Nader, K., Schafe, G. E. & Le Doux, J. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726 (2000).

    Article  ADS  CAS  PubMed  Google Scholar 

  33. Monfils, M.-H., Cowansage, K. K., Klann, E. & LeDoux, J. E. Extinction-reconsolidation boundaries: key to persistent attenuation of fear memories. Science 324, 951–955 (2009).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  34. Schiller, D. et al. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463, 49–53 (2010).

    Article  ADS  CAS  PubMed  Google Scholar 

  35. Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V. & Greicius, M. D. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch. Gen. Psychiatry 66, 1361–1372 (2009).

    Article  PubMed  Google Scholar 

  36. Tye, K. M. et al. Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471, 358–362 (2011). This was the first study to use optogenetic projection-specific manipulations; it showed that activation or inhibition of BLA projections to the CeL nucleus could cause anxiolytic or anxiogenic effects on behaviour, respectively.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  37. Davis, M. The role of the amygdala in fear and anxiety. Annu. Rev. Neurosci. 15, 353–375 (1992).

    Article  CAS  PubMed  Google Scholar 

  38. LeDoux, J. E. Emotion circuits in the brain. Annu. Rev. Neurosci. 23, 155–184 (2000).

    Article  CAS  PubMed  Google Scholar 

  39. Nader, K., Majidishad, P., Amorapanth, P. & LeDoux, J. E. Damage to the lateral and central, but not other, amygdaloid nuclei prevents the acquisition of auditory fear conditioning. Learn. Mem. 8, 156–163 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Collins, D. R. & Paré, D. Differential fear conditioning induces reciprocal changes in the sensory responses of lateral amygdala neurons to the CS+ and CS. Learn. Mem. 7, 97–103 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Maren, S. Auditory fear conditioning increases CS-elicited spike firing in lateral amygdala neurons even after extensive overtraining. Eur. J. Neurosci. 12, 4047–4054 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. Rogan, M. T., Stäubli, U. V. & LeDoux, J. E. Fear conditioning induces associative long-term potentiation in the amygdala. Nature 390, 604–607 (1997).

    Article  ADS  CAS  PubMed  Google Scholar 

  43. McKernan, M. G. & Shinnick-Gallagher, P. Fear conditioning induces a lasting potentiation of synaptic currents in vitro. Nature 390, 607–611 (1997). Along with ref. 42, this was the first evidence to show synaptic enhancement onto LA neurons after fear conditioning.

    Article  ADS  CAS  PubMed  Google Scholar 

  44. Clem, R. L. & Huganir, R. L. Calcium-permeable AMPA receptor dynamics mediate fear memory erasure. Science 330, 1108–1112 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rumpel, S., LeDoux, J., Zador, A. & Malinow, R. Postsynaptic receptor trafficking underlying a form of associative learning. Science 308, 83–88 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  46. Johansen, J. P. et al. Optical activation of lateral amygdala pyramidal cells instructs associative fear learning. Proc. Natl Acad. Sci. USA 107, 12692–12697 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  47. Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348–352 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kapp, B. S., Frysinger, R. C., Gallagher, M. & Haselton, J. R. Amygdala central nucleus lesions: effect on heart rate conditioning in the rabbit. Physiol. Behav. 23, 1109–1117 (1979).

    Article  CAS  PubMed  Google Scholar 

  49. Hitchcock, J. & Davis, M. Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm. Behav. Neurosci. 100, 11–22 (1986).

    Article  CAS  PubMed  Google Scholar 

  50. LeDoux, J. E., Iwata, J., Cicchetti, P. & Reis, D. J. Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear. J. Neurosci. 8, 2517–2529 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Viviani, D. et al. Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science 333, 104–107 (2011).

    Article  ADS  CAS  PubMed  Google Scholar 

  52. Ciocchi, S. et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468, 277–282 (2010).

    Article  ADS  CAS  PubMed  Google Scholar 

  53. Haubensak, W. et al. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468, 270–276 (2010). Together with ref. 52 this study identified functionally and genetically distinct populations of neurons in the CeL in the expression of conditioned fear.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  54. Li, H. et al. Experience-dependent modification of a central amygdala fear circuit. Nature Neurosci. 16, 332–339 (2013). This article reports that experience-dependent plasticity occurs at LA–CeL:SOM+ synapses, demonstrating that amygdala plasticity occurs in more than just the LA.

    Article  CAS  PubMed  Google Scholar 

  55. Penzo, M. A., Robert, V. & Li, B. Fear conditioning potentiates synaptic transmission onto long-range projection neurons in the lateral subdivision of central amygdala. J. Neurosci. 34, 2432–2437 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sparta, D. R. et al. Inhibition of projections from the basolateral amygdala to the entorhinal cortex disrupts the acquisition of contextual fear. Front. Behav. Neurosci. 8, 129 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Knobloch, H. S. et al. Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73, 553–566 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Cai, H., Haubensak, W., Anthony, T. E. & Anderson, D. J. Central amygdala PKC-δ+ neurons mediate the influence of multiple anorexigenic signals. Nature Neurosci. 17, 1240–1248 (2014). This study showed that PKCδ+ neurons suppress feeding and are anxiolytic, and using a 'cre-out' strategy demonstrated opposing functions for PKCδ+ and PKCδ neurons.

    Article  CAS  PubMed  Google Scholar 

  59. Jennings, J. H. et al. Distinct extended amygdala circuits for divergent motivational states. Nature 496, 224–228 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kim, S.-Y. et al. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature 496, 219–223 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  61. Felix-Ortiz, A. C. et al. BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79, 658–664 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Kim, S.-Y. et al. Diverging neural pathways assemble a behavioural state from separable features in anxiety. Nature 496, 219–223 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  63. Felix-Ortiz, A. C. & Tye, K. M. Amygdala inputs to the ventral hippocampus bidirectionally modulate social behavior. J. Neurosci. 34, 586–595 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Allsop, S. A., Vander Weele, C. M., Wichmann, R. & Tye, K. M. Optogenetic insights on the relationship between anxiety-related behaviors and social deficits. Front. Behav. Neurosci. 8, 241 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Wall, N. R., Wickersham, I. R., Cetin, A., De La Parra, M. & Callaway, E. M. Monosynaptic circuit tracing in vivo through Cre-dependent targeting and complementation of modified rabies virus. Proc. Natl Acad. Sci. USA 107, 21848–21853 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  66. Cador, M., Robbins, T. W. & Everitt, B. J. Involvement of the amygdala in stimulus-reward associations: interaction with the ventral striatum. Neuroscience 30, 77–86 (1989).

    Article  CAS  PubMed  Google Scholar 

  67. Everitt, B. J., Cador, M. & Robbins, T. W. Interactions between the amygdala and ventral striatum in stimulus-reward associations: studies using a second-order schedule of sexual reinforcement. Neuroscience 30, 63–75 (1989). This study, along with ref. 66, provided early evidence that amygdala projections to the NAc mediate the effects of Pavlovian stimuli predictive of reward on behaviour.

    Article  CAS  PubMed  Google Scholar 

  68. Gallagher, M., Graham, P. W. & Holland, P. C. The amygdala central nucleus and appetitive Pavlovian conditioning: lesions impair one class of conditioned behavior. J. Neurosci. 10, 1906–1911 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hatfield, T., Han, J. S., Conley, M., Gallagher, M. & Holland, P. Neurotoxic lesions of basolateral, but not central, amygdala interfere with Pavlovian second-order conditioning and reinforcer devaluation effects. J. Neurosci. 16, 5256–5265 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Hiroi, N. & White, N. M. The lateral nucleus of the amygdala mediates expression of the amphetamine-produced conditioned place preference. J. Neurosci. 11, 2107–2116 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. McDonald, R. J. & White, N. M. A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. Behav. Neurosci. 107, 3–22 (1993).

    Article  CAS  PubMed  Google Scholar 

  72. Málková, L., Gaffan, D. & Murray, E. A. Excitotoxic lesions of the amygdala fail to produce impairment in visual learning for auditory secondary reinforcement but interfere with reinforcer devaluation effects in rhesus monkeys. J. Neurosci. 17, 6011–6020 (1997).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Balleine, B. W. & Killcross, S. Parallel incentive processing: an integrated view of amygdala function. Trends Neurosci. 29, 272–279 (2006).

    Article  CAS  PubMed  Google Scholar 

  74. Baxter, M. G. & Murray, E. A. The amygdala and reward. Nature Rev. Neurosci. 3, 563–573 (2002).

    Article  CAS  Google Scholar 

  75. Sanghera, M. K., Rolls, E. T. & Roper-Hall, A. Visual responses of neurons in the dorsolateral amygdala of the alert monkey. Exp. Neurol. 63, 610–626 (1979).

    Article  CAS  PubMed  Google Scholar 

  76. Schoenbaum, G., Chiba, A. A. & Gallagher, M. Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning. Nature Neurosci. 1, 155–159 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Tye, K. M. & Janak, P. H. Amygdala neurons differentially encode motivation and reinforcement. J. Neurosci. 27, 3937–3945 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tye, K. M., Stuber, G. D., de Ridder, B., Bonci, A. & Janak, P. H. Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning. Nature 453, 1253–1257 (2008). This study demonstrated a causal relationship between synaptic potentiation in the amygdala and cue–reward learning, and showed amygdala neurons increase responses in vivo with cue–reward learning.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  79. Uwano, T., Nishijo, H., Ono, T. & Tamura, R. Neuronal responsiveness to various sensory stimuli, and associative learning in the rat amygdala. Neuroscience 68, 339–361 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Belova, M. A., Paton, J. J., Morrison, S. E. & Salzman, C. D. Expectation modulates neural responses to pleasant and aversive stimuli in primate amygdala. Neuron 55, 970–984 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Paton, J. J., Belova, M. A., Morrison, S. E. & Salzman, C. D. The primate amygdala represents the positive and negative value of visual stimuli during learning. Nature 439, 865–870 (2006). In this study, electrophysiological recordings showed that different populations of primate amygdala neurons encoded visual stimuli that predicted positive or negative outcomes.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  82. Schoenbaum, G., Chiba, A. A. & Gallagher, M. Neural encoding in orbitofrontal cortex and basolateral amygdala during olfactory discrimination learning. J. Neurosci. 19, 1876–1884 (1999). This was the first electrophysiological recording study demonstrating the ability of amygdala neurons to track changing outcomes across a reversal task.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shabel, S. J. & Janak, P. H. Substantial similarity in amygdala neuronal activity during conditioned appetitive and aversive emotional arousal. Proc. Natl Acad. Sci. USA 106, 15031–15036 (2009). This study suggested that populations of amygdala neurons that encoded positive and negative outcomes were only partially non-overlapping; the overlapping population may encode salience.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  84. Shabel, S. J., Schairer, W., Donahue, R. J., Powell, V. & Janak, P. H. Similar neural activity during fear and disgust in the rat basolateral amygdala. PLoS ONE 6, e27797 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  85. Sangha, S., Chadick, J. Z. & Janak, P. H. Safety encoding in the basal amygdala. J. Neurosci. 33, 3744–3751 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Herry, C. et al. Switching on and off fear by distinct neuronal circuits. Nature 454, 600–606 (2008).

    Article  ADS  CAS  PubMed  Google Scholar 

  87. Russell, J. A. A circumplex model of affect. J. Personal. Soc. Psychol. 39, 1161–1178 (1980).

    Article  Google Scholar 

  88. Holland, P.C. & Gallagher, M. Amygdala circuitry in attentional and representational processes. Trends Cogn. Sci. 3, 65–73 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Roesch, M. R., Esber, G. R., Li, J., Daw, N. D. & Schoenbaum, G. Surprise! Neural correlates of Pearce-Hall and Rescorla-Wagner coexist within the brain. Eur. J. Neurosci. 35, 1190–1200 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  90. McGaugh, J. L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu. Rev. Neurosci. 27, 1–28 (2004).

    Article  CAS  PubMed  Google Scholar 

  91. Huff, M. L., Miller, R. L., Deisseroth, K., Moorman, D. E. & LaLumiere, R. T. Posttraining optogenetic manipulations of basolateral amygdala activity modulate consolidation of inhibitory avoidance memory in rats. Proc. Natl Acad. Sci. USA 110, 3597–3602 (2013).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  92. Popescu, A. T., Saghyan, A. A. & Paré, D. NMDA-dependent facilitation of corticostriatal plasticity by the amygdala. Proc. Natl Acad. Sci. USA 104, 341–346 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  93. Han, J. S., McMahan, R. W., Holland, P. & Gallagher, M. The role of an amygdalo-nigrostriatal pathway in associative learning. J. Neurosci. 17, 3913–3919 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Vuilleumier, P., Richardson, M. P., Armony, J. L., Driver, J. & Dolan, R. J. Distant influences of amygdala lesion on visual cortical activation during emotional face processing. Nature Neurosci. 7, 1271–1278 (2004).

    Article  CAS  PubMed  Google Scholar 

  95. Peck, C. J. & Salzman, C. D. Amygdala neural activity reflects spatial attention towards stimuli promising reward or threatening punishment. eLife 3, e04478 (2014).

    Article  PubMed Central  Google Scholar 

  96. Zhang, W. et al. Functional circuits and anatomical distribution of response properties in the primate amygdala. J. Neurosci. 33, 722–733 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Han, J.-H. et al. Neuronal competition and selection during memory formation. Science 316, 457–460 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  98. Yiu, A. P. et al. Neurons are recruited to a memory trace based on relative neuronal excitability immediately before training. Neuron 83, 722–735 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Han, J.-H. et al. Selective erasure of a fear memory. Science 323, 1492–1496 (2009). This study provided causal evidence for a stable fear memory engram in the LA by ablating a small proportion of LA neurons overexpressing CREB.

    Article  ADS  CAS  PubMed  Google Scholar 

  100. Hsiang, H.-L. L. et al. Manipulating a 'cocaine engram' in mice. J. Neurosci. 34, 14115–14127 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Reijmers, L. G., Perkins, B. L., Matsuo, N. & Mayford, M. Localization of a stable neural correlate of associative memory. Science 317, 1230–1233 (2007).

    Article  ADS  CAS  PubMed  Google Scholar 

  102. Redondo, R. L. et al. Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513, 426–430 (2014). This study used neuronal tagging to express ChR2 in valence-specific networks, demonstrating that positive and negative valenced networks in the BLA cannot be reversed to the opposite valence by retraining.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  103. Xiu, J. et al. Visualizing an emotional valence map in the limbic forebrain by TAI-FISH. Nature Neurosci. 17, 1552–1559 (2014).

    Article  CAS  PubMed  Google Scholar 

  104. Wolff, S. B. E. et al. Amygdala interneuron subtypes control fear learning through disinhibition. Nature 509, 453–458 (2014). Demonstration of unique roles for PV+ and SOM+ interneurons in combination with in vivo electrophysiology in behaving mice to provide new evidence for inhibitory networks contributing to fear conditioning.

    Article  ADS  CAS  PubMed  Google Scholar 

  105. Cho, J.-H., Deisseroth, K. & Bolshakov, V. Y. Synaptic encoding of fear extinction in mPFC-amygdala circuits. Neuron 80, 1491–1507 (2013).

    Article  CAS  PubMed  Google Scholar 

  106. Trouche, S., Sasaki, J. M., Tu, T. & Reijmers, L. G. Fear extinction causes target-specific remodeling of perisomatic inhibitory synapses. Neuron 80, 1054–1065 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Kelley, A. E., Domesick, V. B. & Nauta, W. J. The amygdalostriatal projection in the rat–an anatomical study by anterograde and retrograde tracing methods. Neuroscience 7, 615–630 (1982).

    Article  CAS  PubMed  Google Scholar 

  108. Ambroggi, F., Ishikawa, A., Fields, H. L. & Nicola, S. M. Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons. Neuron 59, 648–661 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Britt, J. P. et al. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron 76, 790–803 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Stuber, G. D. et al. Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking. Nature 475, 377–380 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Stefanik, M. T. & Kalivas, P. W. Optogenetic dissection of basolateral amygdala projections during cue-induced reinstatement of cocaine seeking. Front. Behav. Neurosci. 7, 213 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Land, B. B. et al. Medial prefrontal D1 dopamine neurons control food intake. Nature Neurosci. 17, 248–253 (2014).

    Article  CAS  PubMed  Google Scholar 

  113. Senn, V. et al. Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 81, 428–437 (2014).

    Article  CAS  PubMed  Google Scholar 

  114. Roberto, M., Gilpin, N. W. & Siggins, G. R. The central amygdala and alcohol: role of γ-aminobutyric acid, glutamate, and neuropeptides. Cold Spring Harb. Perspect. Med. 2, a012195 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Buffalari, D. M. & See, R. E. Amygdala mechanisms of Pavlovian psychostimulant conditioning and relapse. Curr. Top. Behav. Neurosci. 3, 73–99 (2010).

    Article  PubMed  Google Scholar 

  116. Chaudhri, N., Woods, C. A., Sahuque, L. L., Gill, T. M. & Janak, P. H. Unilateral inactivation of the basolateral amygdala attenuates context-induced renewal of Pavlovian-conditioned alcohol-seeking. Eur. J. Neurosci. 38, 2751–2761 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Barak, S. et al. Disruption of alcohol-related memories by mTORC1 inhibition prevents relapse. Nature Neurosci. 16, 1111–1117 (2013).

    Article  CAS  PubMed  Google Scholar 

  118. Baron-Cohen, S. et al. The amygdala theory of autism. Neurosci. Biobehav. Rev. 24, 355–364 (2000).

    Article  CAS  PubMed  Google Scholar 

  119. Saddoris, M. P., Gallagher, M. & Schoenbaum, G. Rapid associative encoding in basolateral amygdala depends on connections with orbitofrontal cortex. Neuron 46, 321–331 (2005).

    Article  CAS  PubMed  Google Scholar 

  120. Morrison, S. E., Saez, A., Lau, B. & Salzman, C. D. Different time courses for learning-related changes in amygdala and orbitofrontal cortex. Neuron 71, 1127–1140 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Seymour, B. & Dolan, R. Emotion, decision making, and the amygdala. Neuron 58, 662–671 (2008).

    Article  CAS  PubMed  Google Scholar 

  122. Likhtik, E., Stujenske, J. M., Topiwala, M. A., Harris, A. Z. & Gordon, J. A. Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety. Nature Neurosci. 17, 106–113 (2014).

    Article  CAS  PubMed  Google Scholar 

  123. Seidenbecher, T., Laxmi, T. R., Stork, O. & Pape, H.-C. Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301, 846–850 (2003).

    Article  ADS  CAS  PubMed  Google Scholar 

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Acknowledgements

P.H.J. acknowledges funding from US National Institutes of Health grants DA015096, AA014925, AA17072. K.M.T. is a New York Stem Cell Foundation-Robertson Investigator and acknowledges funding from the JPB Foundation, PIIF, PNDRF, NARSAD Young Investigator Award, Whitehead Career Development Chair, and NIH grant MH102441. We thank K. Vitale for input regarding interneurons and network selection, G. Calhoon and P. Namburi for input on Fig. 5, R. Keiflin for assistance with Fig. 3, B. Saunders for comments on our text, J. Gabrieli for input on human amygdala research, I. Choi for assistance illustrating Fig. 1 and all the members of our laboratories for valuable discussion.

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Correspondence to Patricia H. Janak or Kay M. Tye.

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Janak, P., Tye, K. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015). https://doi.org/10.1038/nature14188

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