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Retrieving fear memories, as time goes by…

Molecular Psychiatry volume 21, pages 1027–1036 (2016)Cite this article

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Abstract

Research in fear conditioning has provided a comprehensive picture of the neuronal circuit underlying the formation of fear memories. In contrast, our understanding of the retrieval of fear memories is much more limited. This disparity may stem from the fact that fear memories are not rigid, but reorganize over time. To bring some clarity and raise awareness about the time-dependent dynamics of retrieval circuits, we review current evidence on the neuronal circuitry participating in fear memory retrieval at both early and late time points following auditory fear conditioning. We focus on the temporal recruitment of the paraventricular nucleus of the thalamus (PVT) for the retrieval and maintenance of fear memories. Finally, we speculate as to why retrieval circuits change with time, and consider the functional strategy of recruiting structures not previously considered as part of the retrieval circuit.

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References

  1. LeDoux JE . Emotion circuits in the brain. Annu Rev Neurosci 2000; 23: 155–184.

    Article  CAS  PubMed  Google Scholar 

  2. Maren S . Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci 2001; 24: 897–931.

    Article  CAS  PubMed  Google Scholar 

  3. Gale GD, Anagnostaras SG, Godsil BP, Mitchell S, Nozawa T, Sage JR et al. Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats. J Neurosci 2004; 24: 3810–3815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Darwin C (ed). The Expression of the Emotions in Man and Animals. Fontana Press: London, 1872.

    Book  Google Scholar 

  5. LeDoux JE . Evolution of human emotion: a view through fear. Prog Brain Res 2012; 195: 431–442.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nesse RM . Evolutionary explanations of emotions. Hum Nat 1990; 1: 261–289.

    Article  CAS  PubMed  Google Scholar 

  7. Herry C, Johansen JP . Encoding of fear learning and memory in distributed neuronal circuits. Nat Neurosci 2014; 17: 1644–1654.

    Article  CAS  PubMed  Google Scholar 

  8. Duvarci S, Pare D . Amygdala microcircuits controlling learned fear. Neuron 2014; 82: 966–980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Luthi A, Luscher C . Pathological circuit function underlying addiction and anxiety disorders. Nat Neurosci 2014; 17: 1635–1643.

    Article  CAS  PubMed  Google Scholar 

  10. McKenzie S, Eichenbaum H . Consolidation and reconsolidation: two lives of memories? Neuron 2011; 71: 224–233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dudai Y . The restless engram: consolidations never end. Annu Rev Neurosci 2012; 35: 227–247.

    Article  CAS  PubMed  Google Scholar 

  12. Tayler KK, Wiltgen BJ . New methods for understanding systems consolidation. Learn Mem 2013; 20: 553–557.

    Article  PubMed  Google Scholar 

  13. Frankland PW, Bontempi B . The organization of recent and remote memories. Nat Rev Neurosci 2005; 6: 119–130.

    Article  CAS  PubMed  Google Scholar 

  14. Anagnostaras SG, Maren S, Fanselow MS . Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. J Neurosci 1999; 19: 1106–1114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Einarsson EO, Pors J, Nader K . Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression. Neuropsychopharmacology 2015; 40: 480–487.

    Article  CAS  PubMed  Google Scholar 

  16. Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ . The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 2004; 304: 881–883.

    Article  CAS  PubMed  Google Scholar 

  17. Frankland PW, Ding HK, Takahashi E, Suzuki A, Kida S, Silva AJ . Stability of recent and remote contextual fear memory. Learn Mem 2006; 13: 451–457.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gafford GM, Parsons RG, Helmstetter FJ . Memory accuracy predicts hippocampal mTOR pathway activation following retrieval of contextual fear memory. Hippocampus 2013; 23: 842–847.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Goshen I, Brodsky M, Prakash R, Wallace J, Gradinaru V, Ramakrishnan C et al. Dynamics of retrieval strategies for remote memories. Cell 2011; 147: 678–689.

    Article  CAS  PubMed  Google Scholar 

  20. Maren S, Aharonov G, Fanselow MS . Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats. Behav Brain Res 1997; 88: 261–274.

    Article  CAS  PubMed  Google Scholar 

  21. Restivo L, Vetere G, Bontempi B, Ammassari-Teule M . The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex. J Neurosci 2009; 29: 8206–8214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wang SH, Teixeira CM, Wheeler AL, Frankland PW . The precision of remote context memories does not require the hippocampus. Nat Neurosci 2009; 12: 253–255.

    Article  CAS  PubMed  Google Scholar 

  23. Haubrich J, de Freitas Cassini L, Diehl F, Santana F, de Oliveira LF, de Oliveira Alvares L et al. Novel learning accelerates systems consolidation of a contextual fear memory. Hippocampus 2016 (in press).

  24. Beeman CL, Bauer PS, Pierson JL, Quinn JJ . Hippocampus and medial prefrontal cortex contributions to trace and contextual fear memory expression over time. Learn Mem 2013; 20: 336–343.

    Article  PubMed  Google Scholar 

  25. Kwon JT, Jhang J, Kim HS, Lee S, Han JH . Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear. Learn Mem 2012; 19: 487–494.

    Article  PubMed  Google Scholar 

  26. Narayanan RT, Seidenbecher T, Kluge C, Bergado J, Stork O, Pape HC . Dissociated theta phase synchronization in amygdalo- hippocampal circuits during various stages of fear memory. Eur J Neurosci 2007; 25: 1823–1831.

    Article  PubMed  Google Scholar 

  27. Sacco T, Sacchetti B . Role of secondary sensory cortices in emotional memory storage and retrieval in rats. Science 2010; 329: 649–656.

    Article  CAS  PubMed  Google Scholar 

  28. Do-Monte FH, Quinones-Laracuente K, Quirk GJ . A temporal shift in the circuits mediating retrieval of fear memory. Nature 2015; 519: 460–463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Penzo MA, Robert V, Tucciarone J, De Bundel D, Wang M, Van Aelst L et al. The paraventricular thalamus controls a central amygdala fear circuit. Nature 2015; 519: 455–459.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Deisseroth K . Optogenetics: 10 years of microbial opsins in neuroscience. Nat Neurosci 2015; 18: 1213–1225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Corcoran KA, Quirk GJ . Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears. J Neurosci 2007; 27: 840–844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ribeiro AM, Barbosa FF, Munguba H, Costa MS, Cavalcante JS, Silva RH . Basolateral amygdala inactivation impairs learned (but not innate) fear response in rats. Neurobiol Learn Mem 2011; 95: 433–440.

    Article  CAS  PubMed  Google Scholar 

  33. Wang ME, Fraize NP, Yin L, Yuan RK, Petsagourakis D, Wann EG et al. Differential roles of the dorsal and ventral hippocampus in predator odor contextual fear conditioning. Hippocampus 2013; 23: 451–466.

    Article  PubMed  Google Scholar 

  34. Pape HC, Pare D . Plastic synaptic networks of the amygdala for the acquisition, expression, and extinction of conditioned fear. Physiol Rev 2010; 90: 419–463.

    Article  CAS  PubMed  Google Scholar 

  35. Johansen JP, Cain CK, Ostroff LE, LeDoux JE . Molecular mechanisms of fear learning and memory. Cell 2011; 147: 509–524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Watabe AM, Ochiai T, Nagase M, Takahashi Y, Sato M, Kato F . Synaptic potentiation in the nociceptive amygdala following fear learning in mice. Mol Brain 2013; 6: 11.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Wolff SB, Grundemann J, Tovote P, Krabbe S, Jacobson GA, Muller C et al. Amygdala interneuron subtypes control fear learning through disinhibition. Nature 2014; 509: 453–458.

    Article  CAS  PubMed  Google Scholar 

  38. Sehgal M, Ehlers VL, Moyer JR Jr . Learning enhances intrinsic excitability in a subset of lateral amygdala neurons. Learn Mem 2014; 21: 161–170.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sears RM, Schiff HC, LeDoux JE . Molecular mechanisms of threat learning in the lateral nucleus of the amygdala. Prog Mol Biol Transl Sci 2014; 122: 263–304.

    Article  CAS  PubMed  Google Scholar 

  40. Penzo MA, Robert V, Li B . Fear conditioning potentiates synaptic transmission onto long-range projection neurons in the lateral subdivision of central amygdala. J Neurosci 2014; 34: 2432–2437.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Li H, Penzo MA, Taniguchi H, Kopec CD, Huang ZJ, Li B . Experience-dependent modification of a central amygdala fear circuit. Nat Neurosci 2013; 16: 332–339.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Goosens KA, Maren S . Pretraining NMDA receptor blockade in the basolateral complex, but not the central nucleus, of the amygdala prevents savings of conditional fear. Behav Neurosci 2003; 117: 738–750.

    Article  CAS  PubMed  Google Scholar 

  43. Wilensky AE, Schafe GE, Kristensen MP, LeDoux JE . Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning. J Neurosci 2006; 26: 12387–12396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ciocchi S, Herry C, Grenier F, Wolff SB, Letzkus JJ, Vlachos I et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 2010; 468: 277–282.

    Article  CAS  PubMed  Google Scholar 

  45. Anglada-Figueroa D, Quirk GJ . Lesions of the basal amygdala block expression of conditioned fear but not extinction. J Neurosci 2005; 25: 9680–9685.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Goosens KA, Maren S . Contextual and auditory fear conditioning are mediated by the lateral, basal, and central amygdaloid nuclei in rats. Learn Mem 2001; 8: 148–155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sierra-Mercado D, Padilla-Coreano N, Quirk GJ . Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear. Neuropsychopharmacology 2011; 36: 529–538.

    Article  PubMed  Google Scholar 

  48. Koo JW, Han JS, Kim JJ . Selective neurotoxic lesions of basolateral and central nuclei of the amygdala produce differential effects on fear conditioning. J Neurosci 2004; 24: 7654–7662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Pitkanen A, Savander V, LeDoux JE . Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala. Trends Neurosci 1997; 20: 517–523.

    Article  CAS  PubMed  Google Scholar 

  50. Stefanacci L, Farb CR, Pitkanen A, Go G, LeDoux JE, Amaral DG . Projections from the lateral nucleus to the basal nucleus of the amygdala: a light and electron microscopic PHA-L study in the rat. J Comp Neurol 1992; 323: 586–601.

    Article  CAS  PubMed  Google Scholar 

  51. Ottersen OP . Connections of the amygdala of the rat. IV: Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase. J Comp Neurol 1982; 205: 30–48.

    Article  CAS  PubMed  Google Scholar 

  52. Pitkanen A, Stefanacci L, Farb CR, Go GG, LeDoux JE, Amaral DG . Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus. J Comp Neurol 1995; 356: 288–310.

    Article  CAS  PubMed  Google Scholar 

  53. Savander V, Miettinen R, Ledoux JE, Pitkanen A . Lateral nucleus of the rat amygdala is reciprocally connected with basal and accessory basal nuclei: a light and electron microscopic study. Neuroscience 1997; 77: 767–781.

    Article  CAS  PubMed  Google Scholar 

  54. Viviani D, Charlet A, van den Burg E, Robinet C, Hurni N, Abatis M et al. Oxytocin selectively gates fear responses through distinct outputs from the central amygdala. Science 2011; 333: 104–107.

    Article  CAS  PubMed  Google Scholar 

  55. LeDoux JE, Iwata J, Cicchetti P, Reis DJ . Different projections of the central amygdaloid nucleus mediate autonomic and behavioral correlates of conditioned fear. J Neurosci 1988; 8: 2517–2529.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Repa JC, Muller J, Apergis J, Desrochers TM, Zhou Y, LeDoux JE . Two different lateral amygdala cell populations contribute to the initiation and storage of memory. Nat Neurosci 2001; 4: 724–731.

    Article  CAS  PubMed  Google Scholar 

  57. Quirk GJ, Repa C, LeDoux JE . Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: parallel recordings in the freely behaving rat. Neuron 1995; 15: 1029–1039.

    Article  CAS  PubMed  Google Scholar 

  58. Rogan MT, Staubli UV, LeDoux JE . Fear conditioning induces associative long-term potentiation in the amygdala. Nature 1997; 390: 604–607.

    Article  CAS  PubMed  Google Scholar 

  59. Goosens KA, Hobin JA, Maren S . Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: mnemonic code or fear bias? Neuron 2003; 40: 1013–1022.

    Article  CAS  PubMed  Google Scholar 

  60. Diaz-Mataix L, Debiec J, LeDoux JE, Doyere V . Sensory-specific associations stored in the lateral amygdala allow for selective alteration of fear memories. J Neurosci 2011; 31: 9538–9543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Amano T, Duvarci S, Popa D, Pare D . The fear circuit revisited: contributions of the basal amygdala nuclei to conditioned fear. J Neurosci 2011; 31: 15481–15489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Herry C, Ciocchi S, Senn V, Demmou L, Muller C, Luthi A . Switching on and off fear by distinct neuronal circuits. Nature 2008; 454: 600–606.

    Article  CAS  PubMed  Google Scholar 

  63. Duvarci S, Popa D, Pare D . Central amygdala activity during fear conditioning. J Neurosci 2011; 31: 289–294.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Haubensak W, Kunwar PS, Cai H, Ciocchi S, Wall NR, Ponnusamy R et al. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 2010; 468: 270–276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Nitecka L, Ben-Ari Y . Distribution of GABA-like immunoreactivity in the rat amygdaloid complex. J Comp Neurol 1987; 266: 45–55.

    Article  CAS  PubMed  Google Scholar 

  66. Millhouse OE . The intercalated cells of the amygdala. J Comp Neurol 1986; 247: 246–271.

    Article  CAS  PubMed  Google Scholar 

  67. Royer S, Martina M, Pare D . An inhibitory interface gates impulse traffic between the input and output stations of the amygdala. J Neurosci 1999; 19: 10575–10583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Damasio AR . On some functions of the human prefrontal cortex. Ann N Y Acad Sci 1995; 769: 241–251.

    Article  CAS  PubMed  Google Scholar 

  69. Barbas H . Complementary roles of prefrontal cortical regions in cognition, memory, and emotion in primates. Adv Neurol 2000; 84: 87–110.

    CAS  PubMed  Google Scholar 

  70. Morgan MA, Romanski LM, LeDoux JE . Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett 1993; 163: 109–113.

    Article  CAS  PubMed  Google Scholar 

  71. Likhtik E, Stujenske JM, Topiwala MA, Harris AZ, Gordon JA . Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety. Nat Neurosci 2014; 17: 106–113.

    Article  CAS  PubMed  Google Scholar 

  72. Xu W, Sudhof TC . A neural circuit for memory specificity and generalization. Science 2013; 339: 1290–1295.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Do-Monte FH, Manzano-Nieves G, Quinones-Laracuente K, Ramos-Medina L, Quirk GJ . Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 2015; 35: 3607–3615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chang CH, Maren S . Strain difference in the effect of infralimbic cortex lesions on fear extinction in rats. Behav Neurosci 2010; 124: 391–397.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Burgos-Robles A, Vidal-Gonzalez I, Santini E, Quirk GJ . Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex. Neuron 2007; 53: 871–880.

    Article  CAS  PubMed  Google Scholar 

  76. Adhikari A, Lerner TN, Finkelstein J, Pak S, Jennings JH, Davidson TJ et al. Basomedial amygdala mediates top-down control of anxiety and fear. Nature 2015; 527: 179–185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bukalo O, Pinard CR, Silverstein S, Brehm C, Hartley ND, Whittle N et al. Prefrontal inputs to the amygdala instruct fear extinction memory formation. Sci Adv 2015; 1: 6.

    Article  Google Scholar 

  78. Burgos-Robles A, Vidal-Gonzalez I, Quirk GJ . Sustained conditioned responses in prelimbic prefrontal neurons are correlated with fear expression and extinction failure. J Neurosci 2009; 29: 8474–8482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Baeg EH, Kim YB, Jang J, Kim HT, Mook-Jung I, Jung MW . Fast spiking and regular spiking neural correlates of fear conditioning in the medial prefrontal cortex of the rat. Cereb Cortex 2001; 11: 441–451.

    Article  CAS  PubMed  Google Scholar 

  80. Sotres-Bayon F, Quirk GJ . Prefrontal control of fear: more than just extinction. Curr Opin Neurobiol 2010; 20: 231–235.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Karalis N, Dejean C, Chaudun F, Khoder S, Rozeske RR, Wurtz H et al. 4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior. Nat Neurosci 2016; 19: 605–612.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Sotres-Bayon F, Sierra-Mercado D, Pardilla-Delgado E, Quirk GJ . Gating of fear in prelimbic cortex by hippocampal and amygdala inputs. Neuron 2012; 76: 804–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Senn V, Wolff SB, Herry C, Grenier F, Ehrlich I, Grundemann J et al. Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 2014; 81: 428–437.

    Article  CAS  PubMed  Google Scholar 

  84. McDonald AJ, Mascagni F, Guo L . Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience 1996; 71: 55–75.

    Article  CAS  PubMed  Google Scholar 

  85. Vertes RP . Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 2004; 51: 32–58.

    Article  CAS  PubMed  Google Scholar 

  86. Courtin J, Chaudun F, Rozeske RR, Karalis N, Gonzalez-Campo C, Wurtz H et al. Prefrontal parvalbumin interneurons shape neuronal activity to drive fear expression. Nature 2014; 505: 92–96.

    Article  CAS  PubMed  Google Scholar 

  87. Lee AT, Vogt D, Rubenstein JL, Sohal VS . A class of GABAergic neurons in the prefrontal cortex sends long-range projections to the nucleus accumbens and elicits acute avoidance behavior. J Neurosci 2014; 34: 11519–11525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bravo-Rivera C, Diehl MM, Roman-Ortiz C, Rodriguez-Romaguera J, Rosas-Vidal LE, Bravo-Rivera H et al. Long-range GABAergic neurons in the prefrontal cortex modulate behavior. J Neurophysiol 2014; 114: 1357–1359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Quirk GJ, Armony JL, LeDoux JE . Fear conditioning enhances different temporal components of tone-evoked spike trains in auditory cortex and lateral amygdala. Neuron 1997; 19: 613–624.

    Article  CAS  PubMed  Google Scholar 

  90. Romanski LM, LeDoux JE . Bilateral destruction of neocortical and perirhinal projection targets of the acoustic thalamus does not disrupt auditory fear conditioning. Neurosci Lett 1992; 142: 228–232.

    Article  CAS  PubMed  Google Scholar 

  91. Campeau S, Davis M . Involvement of subcortical and cortical afferents to the lateral nucleus of the amygdala in fear conditioning measured with fear-potentiated startle in rats trained concurrently with auditory and visual conditioned stimuli. J Neurosci 1995; 15: 2312–2327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Romanski LM, LeDoux JE . Equipotentiality of thalamo-amygdala and thalamo-cortico-amygdala circuits in auditory fear conditioning. J Neurosci 1992; 12: 4501–4509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. LeDoux JE, Sakaguchi A, Reis DJ . Subcortical efferent projections of the medial geniculate nucleus mediate emotional responses conditioned to acoustic stimuli. J Neurosci 1984; 4: 683–698.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Boatman JA, Kim JJ . A thalamo-cortico-amygdala pathway mediates auditory fear conditioning in the intact brain. Eur J Neurosci 2006; 24: 894–900.

    Article  PubMed  Google Scholar 

  95. Letzkus JJ, Wolff SB, Meyer EM, Tovote P, Courtin J, Herry C et al. A disinhibitory microcircuit for associative fear learning in the auditory cortex. Nature 2011; 480: 331–335.

    Article  CAS  PubMed  Google Scholar 

  96. Weible AP, Liu C, Niell CM, Wehr M . Auditory cortex is required for fear potentiation of gap detection. J Neurosci 2014; 34: 15437–15445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Headley DB, Weinberger NM . Fear conditioning enhances gamma oscillations and their entrainment of neurons representing the conditioned stimulus. J Neurosci 2013; 33: 5705–5717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Grosso A, Cambiaghi M, Renna A, Milano L, Roberto Merlo G, Sacco T et al. The higher order auditory cortex is involved in the assignment of affective value to sensory stimuli. Nat Commun 2015; 6: 8886.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Grosso A, Cambiaghi M, Concina G, Sacco T, Sacchetti B . Auditory cortex involvement in emotional learning and memory. Neuroscience 2015; 299: 45–55.

    Article  CAS  PubMed  Google Scholar 

  100. Vetere G, Restivo L, Cole CJ, Ross PJ, Ammassari-Teule M, Josselyn SA et al. Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory. Proc Natl Acad Sci USA 2011; 108: 8456–8460.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Walters BJ, Zovkic IB . Building up and knocking down: an emerging role for epigenetics and proteasomal degradation in systems consolidation. Neuroscience 2015; 300: 39–52.

    Article  CAS  PubMed  Google Scholar 

  102. Squire LR, Genzel L, Wixted JT, Morris RG . Memory consolidation. Cold Spring Harb Perspect Biol 2015; 7: a021766.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Moscovitch M, Cabeza R, Winocur G, Nadel L . Episodic memory and beyond: the hippocampus and neocortex in transformation. Annu Rev Psychol 2016; 67: 105–134.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Routtenberg A . Lifetime memories from persistently supple synapses. Hippocampus 2013; 23: 202–206.

    Article  PubMed  Google Scholar 

  105. Li S, Kirouac GJ . Sources of inputs to the anterior and posterior aspects of the paraventricular nucleus of the thalamus. Brain Struct Funct 2012; 217: 257–273.

    Article  PubMed  Google Scholar 

  106. Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ . Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 2005; 492: 145–177.

    Article  PubMed  Google Scholar 

  107. Cambiaghi M, Grosso A, Likhtik E, Mazziotti R, Concina G, Renna A et al. Higher-order sensory cortex drives basolateral amygdala activity during the recall of remote, but not recently learned fearful memories. J Neurosci 2016; 36: 1647–1659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Narayanan RT, Seidenbecher T, Sangha S, Stork O, Pape HC . Theta resynchronization during reconsolidation of remote contextual fear memory. Neuroreport 2007; 18: 1107–1111.

    Article  PubMed  Google Scholar 

  109. Poulos AM, Li V, Sterlace SS, Tokushige F, Ponnusamy R, Fanselow MS . Persistence of fear memory across time requires the basolateral amygdala complex. Proc Natl Acad Sci USA 2009; 106: 11737–11741.

    Article  PubMed  PubMed Central  Google Scholar 

  110. Maren S, Aharonov G, Stote DL, Fanselow MS . N-methyl-D-aspartate receptors in the basolateral amygdala are required for both acquisition and expression of conditional fear in rats. Behav Neurosci 1996; 110: 1365–1374.

    Article  CAS  PubMed  Google Scholar 

  111. Antoniadis EA, Winslow JT, Davis M, Amaral DG . Role of the primate amygdala in fear-potentiated startle: effects of chronic lesions in the rhesus monkey. J Neurosci 2007; 27: 7386–7396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Antoniadis EA, Winslow JT, Davis M, Amaral DG . The nonhuman primate amygdala is necessary for the acquisition but not the retention of fear-potentiated startle. Biol Psychiatry 2009; 65: 241–248.

    Article  PubMed  Google Scholar 

  113. Bertocchi I, Arcos-Diaz D, Botta P, Treviño M, Dogbevia G, Luthi A . Cortical localization of fear memory. Abstract Society for Neuroscience Meeting 2014.

  114. Bertocchi I, Arcos-Diaz D, Botta P, Dogbevia G, Luthi A . Fear and aversive learning and memory: amygdala and extended amygdala circuits. Abstract Society for Neuroscience Meeting 2013.

  115. Izquierdo I, Quillfeldt JA, Zanatta MS, Quevedo J, Schaeffer E, Schmitz PK et al. Sequential role of hippocampus and amygdala, entorhinal cortex and parietal cortex in formation and retrieval of memory for inhibitory avoidance in rats. Eur J Neurosci 1997; 9: 786–793.

    Article  CAS  PubMed  Google Scholar 

  116. Liang KC, Hu SJ, Chang SC . Formation and retrieval of inhibitory avoidance memory: differential roles of glutamate receptors in the amygdala and medial prefrontal cortex. Chin J Physiol 1996; 39: 155–166.

    CAS  PubMed  Google Scholar 

  117. Parent MB, Quirarte GL, Cahill L, McGaugh JL . Spared retention of inhibitory avoidance learning after posttraining amygdala lesions. Behav Neurosci 1995; 109: 803–807.

    Article  CAS  PubMed  Google Scholar 

  118. McIntyre CK, Power AE, Roozendaal B, McGaugh JL . Role of the basolateral amygdala in memory consolidation. Ann N Y Acad Sci 2003; 985: 273–293.

    Article  CAS  PubMed  Google Scholar 

  119. Euston DR, Gruber AJ, McNaughton BL . The role of medial prefrontal cortex in memory and decision making. Neuron 2012; 76: 1057–1070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Moga MM, Weis RP, Moore RY . Efferent projections of the paraventricular thalamic nucleus in the rat. J Comp Neurol 1995; 359: 221–238.

    Article  CAS  PubMed  Google Scholar 

  121. Vertes RP, Hoover WB . Projections of the paraventricular and paratenial nuclei of the dorsal midline thalamus in the rat. J Comp Neurol 2008; 508: 212–237.

    Article  PubMed  Google Scholar 

  122. Cornwall J, Phillipson OT . Afferent projections to the dorsal thalamus of the rat as shown by retrograde lectin transport. II. The midline nuclei. Brain Res Bull 1988; 21: 147–161.

    Article  CAS  PubMed  Google Scholar 

  123. Li S, Kirouac GJ . Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala. J Comp Neurol 2008; 506: 263–287.

    Article  PubMed  Google Scholar 

  124. Padilla-Coreano N, Do-Monte FH, Quirk GJ . A time-dependent role of midline thalamic nuclei in the retrieval of fear memory. Neuropharmacology 2012; 62: 457–463.

    Article  CAS  PubMed  Google Scholar 

  125. Li Y, Dong X, Li S, Kirouac GJ . Lesions of the posterior paraventricular nucleus of the thalamus attenuate fear expression. Front Behav Neurosci 2014; 8: 94.

    PubMed  PubMed Central  Google Scholar 

  126. Ferrero P, Guidotti A, Costa E . Increase in the Bmax of gamma-aminobutyric acid-A recognition sites in brain regions of mice receiving diazepam. Proc Natl Acad Sci USA 1984; 81: 2247–2251.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Alexander GM, Rogan SC, Abbas AI, Armbruster BN, Pei Y, Allen JA et al. Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron 2009; 63: 27–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Sengupta A, McNally GP . A role for midline and intralaminar thalamus in the associative blocking of Pavlovian fear conditioning. Front Behav Neurosci 2014; 8: 148.

    Article  PubMed  PubMed Central  Google Scholar 

  129. Furlong TM, Richardson R, McNally GP . Habituation and extinction of fear recruit overlapping forebrain structures. Neurobiol Learn Mem 2016; 128: 7–16.

    Article  PubMed  Google Scholar 

  130. Helmchen F, Denk W, Kerr JN . Miniaturization of two-photon microscopy for imaging in freely moving animals. Cold Spring Harb Protoc 2013; 2013: 904–913.

    Article  PubMed  Google Scholar 

  131. Chen JL, Andermann ML, Keck T, Xu NL, Ziv Y . Imaging neuronal populations in behaving rodents: paradigms for studying neural circuits underlying behavior in the mammalian cortex. J Neurosci 2013; 33: 17631–17640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Spencer SJ, Fox JC, Day TA . Thalamic paraventricular nucleus lesions facilitate central amygdala neuronal responses to acute psychological stress. Brain Res 2004; 997: 234–237.

    Article  CAS  PubMed  Google Scholar 

  133. Ottersen OP, Storm-Mathisen J . Glutamate- and GABA-containing neurons in the mouse and rat brain, as demonstrated with a new immunocytochemical technique. J Comp Neurol 1984; 229: 374–392.

    Article  CAS  PubMed  Google Scholar 

  134. Bentivoglio M, Balercia G, Kruger L . The specificity of the nonspecific thalamus: the midline nuclei. Prog Brain Res 1991; 87: 53–80.

    Article  CAS  PubMed  Google Scholar 

  135. Frassoni C, Spreafico R, Bentivoglio M . Glutamate, aspartate and co-localization with calbindin in the medial thalamus. An immunohistochemical study in the rat. Exp Brain Res 1997; 115: 95–104.

    Article  CAS  PubMed  Google Scholar 

  136. Alamilla J, Aguilar-Roblero R . Glutamate and GABA neurotransmission from the paraventricular thalamus to the suprachiasmatic nuclei in the rat. J Biol Rhythms 2010; 25: 28–36.

    Article  CAS  PubMed  Google Scholar 

  137. Lu B, Nagappan G, Lu Y . BDNF and synaptic plasticity, cognitive function, and dysfunction. Handb Exp Pharmacol 2014; 220: 223–250.

    Article  CAS  PubMed  Google Scholar 

  138. Zagrebelsky M, Korte M . Form follows function: BDNF and its involvement in sculpting the function and structure of synapses. Neuropharmacology 2014; 76: 628–638.

    Article  CAS  PubMed  Google Scholar 

  139. Cunha C, Brambilla R, Thomas KL . A simple role for BDNF in learning and memory? Front Mol Neurosci 2010; 3: 1.

    PubMed  PubMed Central  Google Scholar 

  140. Rattiner LM, Davis M, French CT, Ressler KJ . Brain-derived neurotrophic factor and tyrosine kinase receptor B involvement in amygdala-dependent fear conditioning. J Neurosci 2004; 24: 4796–4806.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Andero R, Heldt SA, Ye K, Liu X, Armario A, Ressler KJ . Effect of 7,8-dihydroxyflavone, a small-molecule TrkB agonist, on emotional learning. Am J Psychiatry 2011; 168: 163–172.

    Article  PubMed  Google Scholar 

  142. Rosas-Vidal LE, Do-Monte FH, Sotres-Bayon F, Quirk GJ . Hippocampal—prefrontal BDNF and memory for fear extinction. Neuropsychopharmacology 2014; 39: 2161–2169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Peters J, Dieppa-Perea LM, Melendez LM, Quirk GJ . Induction of fear extinction with hippocampal-infralimbic BDNF. Science 2010; 328: 1288–1290.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A et al. BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci USA 2008; 105: 2711–2716.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Ou LC, Yeh SH, Gean PW . Late expression of brain-derived neurotrophic factor in the amygdala is required for persistence of fear memory. Neurobiol Learn Mem 2010; 93: 372–382.

    Article  CAS  PubMed  Google Scholar 

  146. Nader K, Schafe GE, Le Doux JE . Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 2000; 406: 722–726.

    Article  CAS  PubMed  Google Scholar 

  147. Wiegert JS, Bading H . Activity-dependent calcium signaling and ERK-MAP kinases in neurons: a link to structural plasticity of the nucleus and gene transcription regulation. Cell Calcium 2011; 49: 296–305.

    Article  CAS  PubMed  Google Scholar 

  148. Baker KD, Richardson R . Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit. Learn Mem 2015; 22: 537–543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Bontempi B, Laurent-Demir C, Destrade C, Jaffard R . Time-dependent reorganization of brain circuitry underlying long-term memory storage. Nature 1999; 400: 671–675.

    Article  CAS  PubMed  Google Scholar 

  150. Matyas F, Lee J, Shin HS, Acsady L . The fear circuit of the mouse forebrain: connections between the mediodorsal thalamus, frontal cortices and basolateral amygdala. Eur J Neurosci 2014; 39: 1810–1823.

    Article  PubMed  Google Scholar 

  151. Hsu DT, Kirouac GJ, Zubieta JK, Bhatnagar S . Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood. Front Behav Neurosci 2014; 8: 73.

    PubMed  PubMed Central  Google Scholar 

  152. Kirouac GJ . Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior. Neurosci Biobehav Rev 2015; 56: 315–329.

    Article  PubMed  Google Scholar 

  153. Chen S, Su HS . Afferent connections of the thalamic paraventricular and parataenial nuclei in the rat—a retrograde tracing study with iontophoretic application of Fluoro-Gold. Brain Res 1990; 522: 1–6.

    Article  CAS  PubMed  Google Scholar 

  154. Lee JS, Lee EY, Lee HS . Hypothalamic, feeding/arousal-related peptidergic projections to the paraventricular thalamic nucleus in the rat. Brain Res 2015; 1598: 97–113.

    Article  CAS  PubMed  Google Scholar 

  155. Bhatnagar S, Dallman M . Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress. Neuroscience 1998; 84: 1025–1039.

    Article  CAS  PubMed  Google Scholar 

  156. O'Mahony CM, Sweeney FF, Daly E, Dinan TG, Cryan JF . Restraint stress-induced brain activation patterns in two strains of mice differing in their anxiety behaviour. Behav Brain Res 2010; 213: 148–154.

    Article  PubMed  Google Scholar 

  157. Bubser M, Deutch AY . Stress induces Fos expression in neurons of the thalamic paraventricular nucleus that innervate limbic forebrain sites. Synapse 1999; 32: 13–22.

    Article  CAS  PubMed  Google Scholar 

  158. Semba K, Pastorius J, Wilkinson M, Rusak B . Sleep deprivation-induced c-fos and junB expression in the rat brain: effects of duration and timing. Behav Brain Res 2001; 120: 75–86.

    Article  CAS  PubMed  Google Scholar 

  159. Cullinan WE, Herman JP, Battaglia DF, Akil H, Watson SJ . Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 1995; 64: 477–505.

    Article  CAS  PubMed  Google Scholar 

  160. Zhu L, Wu L, Yu B, Liu X . The participation of a neurocircuit from the paraventricular thalamus to amygdala in the depressive like behavior. Neurosci Lett 2011; 488: 81–86.

    Article  CAS  PubMed  Google Scholar 

  161. Bhatnagar S, Huber R, Nowak N, Trotter P . Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint. J Neuroendocrinol 2002; 14: 403–410.

    Article  CAS  PubMed  Google Scholar 

  162. Jaferi A, Nowak N, Bhatnagar S . Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus. Physiol Behav 2003; 78: 365–373.

    Article  CAS  PubMed  Google Scholar 

  163. Colavito V, Tesoriero C, Wirtu AT, Grassi-Zucconi G, Bentivoglio M . Limbic thalamus and state-dependent behavior: The paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep/wake-regulatory networks. Neurosci Biobehav Rev 2015; 54: 3–17.

    Article  PubMed  Google Scholar 

  164. Heydendael W, Sharma K, Iyer V, Luz S, Piel D, Beck S et al. Orexins/hypocretins act in the posterior paraventricular thalamic nucleus during repeated stress to regulate facilitation to novel stress. Endocrinology 2011; 152: 4738–4752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Kasahara T, Takata A, Kato TM, Kubota-Sakashita M, Sawada T, Kakita A et al. Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus. Mol Psychiatry 2015; 21: 39–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ . Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats. Psychopharmacology (Berl) 2010; 212: 251–265.

    Article  CAS  Google Scholar 

  167. Li Y, Li S, Wei C, Wang H, Sui N, Kirouac GJ . Changes in emotional behavior produced by orexin microinjections in the paraventricular nucleus of the thalamus. Pharmacol Biochem Behav 2010; 95: 121–128.

    Article  CAS  PubMed  Google Scholar 

  168. Matzeu A, Zamora-Martinez ER, Martin-Fardon R . The paraventricular nucleus of the thalamus is recruited by both natural rewards and drugs of abuse: recent evidence of a pivotal role for orexin/hypocretin signaling in this thalamic nucleus in drug-seeking behavior. Front Behav Neurosci 2014; 8: 117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Russo SJ, Nestler EJ . The brain reward circuitry in mood disorders. Nat Rev Neurosci 2013; 14: 609–625.

    Article  CAS  PubMed  Google Scholar 

  170. Igelstrom KM, Herbison AE, Hyland BI . Enhanced c-Fos expression in superior colliculus, paraventricular thalamus and septum during learning of cue-reward association. Neuroscience 2010; 168: 706–714.

    Article  CAS  PubMed  Google Scholar 

  171. Schiltz CA, Bremer QZ, Landry CF, Kelley AE . Food-associated cues alter forebrain functional connectivity as assessed with immediate early gene and proenkephalin expression. BMC Biol 2007; 5: 16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Dayas CV, McGranahan TM, Martin-Fardon R, Weiss F . Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse. Biol Psychiatry 2008; 63: 152–157.

    Article  CAS  PubMed  Google Scholar 

  173. James MH, Charnley JL, Flynn JR, Smith DW, Dayas CV . Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei. Neuroscience 2011; 199: 235–242.

    Article  CAS  PubMed  Google Scholar 

  174. Matzeu A, Cauvi G, Kerr TM, Weiss F, Martin-Fardon R . The paraventricular nucleus of the thalamus is differentially recruited by stimuli conditioned to the availability of cocaine versus palatable food. Addict Biol 2016 (in press).

  175. Yasoshima Y, Scott TR, Yamamoto T . Differential activation of anterior and midline thalamic nuclei following retrieval of aversively motivated learning tasks. Neuroscience 2007; 146: 922–930.

    Article  CAS  PubMed  Google Scholar 

  176. Beck CH, Fibiger HC . Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J Neurosci 1995; 15: 709–720.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Zhu Y, Wienecke CF, Nachtrab G, Chen X . A thalamic input to the nucleus accumbens mediates opiate dependence. Nature 2016; 530: 219–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Urstadt KR, Stanley BG . Direct hypothalamic and indirect trans-pallidal, trans-thalamic, or trans-septal control of accumbens signaling and their roles in food intake. Front Syst Neurosci 2015; 9: 8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Hamlin AS, Clemens KJ, Choi EA, McNally GP . Paraventricular thalamus mediates context-induced reinstatement (renewal) of extinguished reward seeking. Eur J Neurosci 2009; 29: 802–812.

    Article  PubMed  Google Scholar 

  180. Parsons MP, Li S, Kirouac GJ . Functional and anatomical connection between the paraventricular nucleus of the thalamus and dopamine fibers of the nucleus accumbens. J Comp Neurol 2007; 500: 1050–1063.

    Article  CAS  PubMed  Google Scholar 

  181. Namburi P, Beyeler A, Yorozu S, Calhoon GG, Halbert SA, Wichmann R et al. A circuit mechanism for differentiating positive and negative associations. Nature 2015; 520: 675–678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Shabel SJ, Janak PH . Substantial similarity in amygdala neuronal activity during conditioned appetitive and aversive emotional arousal. Proc Natl Acad Sci USA 2009; 106: 15031–15036.

    Article  PubMed  PubMed Central  Google Scholar 

  183. Grundemann J, Luthi A . Ensemble coding in amygdala circuits for associative learning. Curr Opin Neurobiol 2015; 35: 200–206.

    Article  CAS  PubMed  Google Scholar 

  184. Janak PH, Tye KM . From circuits to behaviour in the amygdala. Nature 2015; 517: 284–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Salazar-Juarez A, Escobar C, Aguilar-Roblero R . Anterior paraventricular thalamus modulates light-induced phase shifts in circadian rhythmicity in rats. Am J Physiol Regul Integr Comp Physiol 2002; 283: R897–R904.

    Article  PubMed  Google Scholar 

  186. Zhang L, Kolaj M, Renaud LP . Suprachiasmatic nucleus communicates with anterior thalamic paraventricular nucleus neurons via rapid glutamatergic and gabaergic neurotransmission: state-dependent response patterns observed in vitro. Neuroscience 2006; 141: 2059–2066.

    Article  CAS  PubMed  Google Scholar 

  187. Stephan FK, Berkley KJ, Moss RL . Efferent connections of the rat suprachiasmatic nucleus. Neuroscience 1981; 6: 2625–2641.

    Article  CAS  PubMed  Google Scholar 

  188. Rosenwasser AM, Turek FW . Neurobiology of circadian rhythm regulation. Sleep Med Clin 2015; 10: 403–412.

    Article  PubMed  Google Scholar 

  189. Novak CM, Smale L, Nunez AA . Rhythms in Fos expression in brain areas related to the sleep-wake cycle in the diurnal Arvicanthis niloticus. Am J Physiol Regul Integr Comp Physiol 2000; 278: R1267–R1274.

    Article  CAS  PubMed  Google Scholar 

  190. Kolaj M, Zhang L, Ronnekleiv OK, Renaud LP . Midline thalamic paraventricular nucleus neurons display diurnal variation in resting membrane potentials, conductances, and firing patterns in vitro. J Neurophysiol 2012; 107: 1835–1844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Watts AG, Swanson LW, Sanchez-Watts G . Efferent projections of the suprachiasmatic nucleus: I. Studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat. J Comp Neurol 1987; 258: 204–229.

    Article  CAS  PubMed  Google Scholar 

  192. Alamilla J, Granados-Fuentes D, Aguilar-Roblero R . The anterior paraventricular thalamus modulates neuronal excitability in the suprachiasmatic nuclei of the rat. Eur J Neurosci 2015; 42: 2833–2842.

    Article  PubMed  PubMed Central  Google Scholar 

  193. Fenoglio KA, Chen Y, Baram TZ . Neuroplasticity of the hypothalamic-pituitary-adrenal axis early in life requires recurrent recruitment of stress-regulating brain regions. J Neurosci 2006; 26: 2434–2442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Bhatnagar S, Huber R, Lazar E, Pych L, Vining C . Chronic stress alters behavior in the conditioned defensive burying test: role of the posterior paraventricular thalamus. Pharmacol Biochem Behav 2003; 76: 343–349.

    Article  CAS  PubMed  Google Scholar 

  195. McClelland JL . Incorporating rapid neocortical learning of new schema-consistent information into complementary learning systems theory. J Exp Psychol Gen 2013; 142: 1190–1210.

    Article  PubMed  Google Scholar 

  196. Winocur G, Moscovitch M . Memory transformation and systems consolidation. J Int Neuropsychol Soc 2011; 17: 766–780.

    Article  PubMed  Google Scholar 

  197. American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edn. Washington, DC, 2013.

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Acknowledgements

This work was supported by NIMH grant K99-MH105549 to F.H.D.-M.; NIMH grants R37-MH058883 and P50-MH086400 to G.J.Q.; NIMH grant R01-MH101214 to B.L.; and the Intramural Research Program of the NIMH to M.A.P.

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Authors and Affiliations

  1. Department of Psychiatry and Anatomy & Neurobiology, Laboratory of Fear Learning, University of Puerto Rico School of Medicine, San Juan, Puerto Rico

    F H Do Monte & G J Quirk

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    B Li

  3. Unit on the Neurobiology of Affective Memory, National Institute of Mental Health, Bethesda, MD, USA

    M A Penzo

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  1. F H Do Monte
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Do Monte, F., Quirk, G., Li, B. et al. Retrieving fear memories, as time goes by…. Mol Psychiatry 21, 1027–1036 (2016). https://doi.org/10.1038/mp.2016.78

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