Neurocircuit differences between memory traces of persistent hypoactivity and freezing following fear conditioning among the amygdala, hippocampus, and prefrontal cortex

Masatoshi Takita; Yumi Izawa-Sugaya; Masatoshi Takita; Yumi Izawa-Sugaya

doi:10.3934/Neuroscience.2021010

AIMS Neuroscience

2021, Volume 8, Issue 2: 195-211. doi: 10.3934/Neuroscience.2021010

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Neurocircuit differences between memory traces of persistent hypoactivity and freezing following fear conditioning among the amygdala, hippocampus, and prefrontal cortex

Masatoshi Takita ^{1,2
,
,},
Yumi Izawa-Sugaya ^1,3

1.
Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8566, Japan
2.
Center for Neuroscience and Biomedical Engineering, The University of Electro-Communications, Tokyo, Japan
3.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan

Received: 12 November 2020 Accepted: 07 December 2020 Published: 19 January 2021

We aimed to investigate the persistent trace of one traumatic event on neurocircuit controls in rats. Conditioning was reflected by reductions in rates of ‘freezing’ and ‘other-than-freezing’ motor activities, between which rats could alternate on delivery of pulsed footshocks of intensity 0.5 mA but not 1.0 mA. At the latter intensity, freezing began to suppress motor activity. The conditional responses evident during both the context and tone sessions persisted when the tests were repeated on post-conditioning days 7 and 8. Thus, difficulties with fear extinction/reduction remained. However, persistence was not evident on post-conditioning days 1 and 2. One day after the 1.0 mA pulsed footshock, ibotenate lesions and corresponding sham surgeries were performed in unilateral and bilateral hemispheres of the amygdala, hippocampus, and prefrontal cortex, as well as three different disconnections (one unilateral and another contralateral lesions out of three regions, a total of nine groups), and were tested on days 7–8. The drastic restoration of freezing following bilateral amygdala lesions was also evident in animals with three types of disconnection; however, this was not the case for hypoactivity. These results imply that a serious experience can drive different neurocircuits that all involve the amygdala, forming persistent concurrent memories of explicit (e.g., ‘freezing’) or implicit (e.g., ‘other-than-freezing’ motor activity) emotions, which may exhibit mutual interference.
- extinction,
- footshock intensity,
- freezing,
- ibotenic acid,
- motor activity,
- rats
Citation: Masatoshi Takita, Yumi Izawa-Sugaya. Neurocircuit differences between memory traces of persistent hypoactivity and freezing following fear conditioning among the amygdala, hippocampus, and prefrontal cortex[J]. AIMS Neuroscience, 2021, 8(2): 195-211. doi: 10.3934/Neuroscience.2021010

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Abstract

We aimed to investigate the persistent trace of one traumatic event on neurocircuit controls in rats. Conditioning was reflected by reductions in rates of ‘freezing’ and ‘other-than-freezing’ motor activities, between which rats could alternate on delivery of pulsed footshocks of intensity 0.5 mA but not 1.0 mA. At the latter intensity, freezing began to suppress motor activity. The conditional responses evident during both the context and tone sessions persisted when the tests were repeated on post-conditioning days 7 and 8. Thus, difficulties with fear extinction/reduction remained. However, persistence was not evident on post-conditioning days 1 and 2. One day after the 1.0 mA pulsed footshock, ibotenate lesions and corresponding sham surgeries were performed in unilateral and bilateral hemispheres of the amygdala, hippocampus, and prefrontal cortex, as well as three different disconnections (one unilateral and another contralateral lesions out of three regions, a total of nine groups), and were tested on days 7–8. The drastic restoration of freezing following bilateral amygdala lesions was also evident in animals with three types of disconnection; however, this was not the case for hypoactivity. These results imply that a serious experience can drive different neurocircuits that all involve the amygdala, forming persistent concurrent memories of explicit (e.g., ‘freezing’) or implicit (e.g., ‘other-than-freezing’ motor activity) emotions, which may exhibit mutual interference.

Acknowledgments

We thank Drs. T. Tazumi (Bunkyo University), T. Iwaki (Komazawa University) and M. Ueno (University of Tsukuba) for useful comments on this study and Ms. Atsuko Yamashita for technical assistance. This work was supported in part by a Research Grant for LRI from JCIA (M.T.), a Grant-in-Aid for Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (23530972, 15K042021, and 18K03196 to M.T.), and an AIST grant for neurorehabilitation research.

Conflict of interest

The authors declare no conflict of interest.

References

[1]	LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23: 155-184. doi: 10.1146/annurev.neuro.23.1.155
[2]	Maren S (2001) Neurobiology of Pavlovian fear conditioning. Annu Rev Neurosci 24: 897-931. doi: 10.1146/annurev.neuro.24.1.897
[3]	Quirk GJ, Mueller D (2008) Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology 33: 56-72. doi: 10.1038/sj.npp.1301555
[4]	McSweeney FK, Swindell S (2002) Common processes may contribute to extinction and habituation. J Gen Psychol 129: 364-400. doi: 10.1080/00221300209602103
[5]	Thompson RF, Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73: 16-43. doi: 10.1037/h0022681
[6]	Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106: 274-285. doi: 10.1037/0735-7044.106.2.274
[7]	Kestenbaum R, Celman SA (1995) Preschool children's identification and understanding of mixed emotions. Cognit Dev 10: 443-458. doi: 10.1016/0885-2014(95)90006-3
[8]	Scrimin S, Moscardino U, Capello F, et al. (2009) Recognition of facial expressions of mixed emotions in school-age children exposed to terrorism. Dev Psychol 45: 1341-1352. doi: 10.1037/a0016689
[9]	Shin LM, Rauch SL, Pitman RK (2006) Amygdala, medial prefrontal cortex, and hippocampal function in PTSD. Ann N Y Acad Sci 1071: 67-79. doi: 10.1196/annals.1364.007
[10]	Bandelow B, Zohar J, Hollander E, et al. (2002) World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders-first revision. World J Biol Psychiatry 9: 248-312. doi: 10.1080/15622970802465807
[11]	Corley MJ, Caruso MJ, Takahashi LK (2012) Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder. Physiol Behav 105: 408-416. doi: 10.1016/j.physbeh.2011.08.037
[12]	Wilensky AE, Schafe GE, Kristensen MP, et al. (2006) Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning. J Neurosci 26: 12387-12396. doi: 10.1523/JNEUROSCI.4316-06.2006
[13]	Bast T, Zhang WN, Feldon J (2001) The ventral hippocampus and fear conditioning in rats. Different anterograde amnesias of fear after tetrodotoxin inactivation and infusion of the GABA(A) agonist muscimol. Exp Brain Res 139: 39-52. doi: 10.1007/s002210100746
[14]	Maren S (1999) Long-term potentiation in the amygdala: a mechanism for emotional learning and memory. Trends Neurosci 22: 561-567. doi: 10.1016/S0166-2236(99)01465-4
[15]	Richmond MA, Yee BK, Pouzet B, et al. (1999) Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning. Behav Neurosci 113: 1189-1203. doi: 10.1037/0735-7044.113.6.1189
[16]	Lacroix L, Spinelli S, Heidbreder CA, et al. (2000) Differential role of the medial and lateral prefrontal cortices in fear and anxiety. Behav Neurosci 114: 1119-1130. doi: 10.1037/0735-7044.114.6.1119
[17]	Morgan MA, LeDoux JE (1995) Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats. Behav Neurosci 109: 681-688. doi: 10.1037/0735-7044.109.4.681
[18]	Morgan MA, Romanski LM, LeDoux JE (1993) Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci Lett 163: 109-113. doi: 10.1016/0304-3940(93)90241-C
[19]	Quirk GJ, Russo GK, Barron JL, et al. (2000) The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci 20: 6225-6231. doi: 10.1523/JNEUROSCI.20-16-06225.2000
[20]	Canteras NS, Swanson LW (1992) Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: a PHAL anterograde tract-tracing study in the rat. J Comp Neurol 324: 180-194. doi: 10.1002/cne.903240204
[21]	Krettek JE, Price JL (1974) A direct input from the amygdala to the thalamus and the cerebral cortex. Brain Res 67: 169-174. doi: 10.1016/0006-8993(74)90309-6
[22]	Krettek JE, Price JL (1977) Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat. J Comp Neurol 172: 687-722. doi: 10.1002/cne.901720408
[23]	Ottersen OP (1982) Connections of the amygdala of the rat. IV: Corticoamygdaloid and intraamygdaloid connections as studied with axonal transport of horseradish peroxidase. J Comp Neurol 205: 30-48. doi: 10.1002/cne.902050104
[24]	Pitkänen A (2000) Connectivity of the rat amygdaloid complex. The Amygdala: A Functional Analysis New York: Oxford University Press, 31-115.
[25]	Shi CJ, Cassell MD (1999) Perirhinal cortex projections to the amygdaloid complex and hippocampal formation in the rat. J Comp Neurol 406: 299-328. doi: 10.1002/(SICI)1096-9861(19990412)406:3<299::AID-CNE2>3.0.CO;2-9
[26]	Krettek JE, Price JL (1974) Projections from the amygdala to the perirhinal and entorhinal cortices and the subiculum. Brain Res 17: 150-154. doi: 10.1016/0006-8993(74)90199-1
[27]	Krettek JE, Price JL (1977) Projections from the amygdaloid complex and adjacent olfactory structures to the entorhinal cortex and to the subiculum in the rat and cat. J Comp Neurol 2: 723-752. doi: 10.1002/cne.901720409
[28]	Petrovich GD, Risold PY, Swanson LW (1996) Organization of projections from the basomedial nucleus of the amygdala: a PHAL study in the rat. J Comp Neurol 374: 387-420. doi: 10.1002/(SICI)1096-9861(19961021)374:3<387::AID-CNE6>3.0.CO;2-Y
[29]	Sarter M, Markowitsch HJ (1984) Collateral innervation of the medial and lateral prefrontal cortex by amygdaloid, thalamic, and brain-stem neurons. J Comp Neurol 224: 445-460. doi: 10.1002/cne.902240312
[30]	Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51: 32-58. doi: 10.1002/syn.10279
[31]	McDonald AJ (1987) Organization of amygdaloid projections to the mediodorsal thalamus and prefrontal cortex: a fluorescence retrograde transport study in the rat. J Comp Neurol 262: 46-58. doi: 10.1002/cne.902620105
[32]	McDonald AJ, Mascagni F, Guo L (1996) Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat. Neuroscience 71: 55-75. doi: 10.1016/0306-4522(95)00417-3
[33]	Ferino F, Thierry AM, Glowinski J (1987) Anatomical and electrophysiological evidence for a direct projection from Ammon's horn to the medial prefrontal cortex in the rat. Exp Brain Res 65: 421-426. doi: 10.1007/BF00236315
[34]	Swanson LW (1981) A direct projection from Ammon's horn to prefrontal cortex in the rat. Brain Res 217: 150-154. doi: 10.1016/0006-8993(81)90192-X
[35]	Takita M, Fujiwara SE, Izaki Y (2013) Functional structure of the intermediate and ventral hippocampo-prefrontal pathway in the prefrontal convergent system. J Physiol Paris 107: 441-447. doi: 10.1016/j.jphysparis.2013.05.002
[36]	Herry C, Ferraguti F, Singewald N, et al. (2010) Neuronal circuits of fear extinction. Eur J Neurosci 31: 599-612. doi: 10.1111/j.1460-9568.2010.07101.x
[37]	Canteras NS, Resstel LB, Bertoglio LJ, et al. (2010) Neuroanatomy of anxiety. Curr Top Behav Neurosci 2: 77-96. doi: 10.1007/7854_2009_7
[38]	Singewald N, Holmes A (2019) Rodent models of impaired fear extinction. Psychopharmacology (Berl) 236: 21-32. doi: 10.1007/s00213-018-5054-x
[39]	Izaki Y, Takita M, Akema T (2008) Specific role of the posterior dorsal hippocampus-prefrontal cortex in short-term working memory. Eur J Neurosci 27: 3029-3034. doi: 10.1111/j.1460-9568.2008.06284.x
[40]	Paxinos G, Watson G (1998) The rat brain in stereotaxic coordinates Sydney: Academic.
[41]	Floresco SB, Seamans JK, Phillips AG (1997) Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay. J Neurosci 17: 1880-1890. doi: 10.1523/JNEUROSCI.17-05-01880.1997
[42]	Bouton ME (2004) Context and behavioral processes in extinction. Learn Mem 11: 485-494. doi: 10.1101/lm.78804
[43]	Dudai Y (2006) Reconsolidation: the advantage of being refocused. Curr Opin Neurobiol 16: 174-178. doi: 10.1016/j.conb.2006.03.010
[44]	Dudai Y, Eisenberg M (2004) Rites of passage of the engram: reconsolidation and the lingering consolidation hypothesis. Neuron 44: 93-100. doi: 10.1016/j.neuron.2004.09.003
[45]	Eysenck HJ (1968) A theory of the incubation of anxiety-fear responses. Behav Res Ther 6: 309-321. doi: 10.1016/0005-7967(68)90064-8
[46]	Houston FP, Stevenson GD, McNaughton BL, et al. (1999) Effects of age on the generalization and incubation of memory in the F344 rat. Learn Mem 6: 111-119.
[47]	Rapaport MH, Clary C, Fayyad R, et al. (2005) Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry 162: 1171-1178. doi: 10.1176/appi.ajp.162.6.1171
[48]	Bouton ME, Bolles RC (1980) Conditioned Fear Assessed by Freezing and by the Suppression of 3 Different Baselines. Anim Learn Behav 8: 429-434. doi: 10.3758/BF03199629
[49]	Amorapanth P, Nader K, LeDoux JE (1999) Lesions of periaqueductal gray dissociate-conditioned freezing from conditioned suppression behavior in rats. Learn Mem 6: 491-499. doi: 10.1101/lm.6.5.491
[50]	Kim JJ, Rison RA, Fanselow MS (1993) Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear. Behav Neurosci 107: 1093-1098. doi: 10.1037/0735-7044.107.6.1093
[51]	Vianna DM, Graeff FG, Landeira-Fernandez J, et al. (2001) Lesion of the ventral periaqueductal gray reduces conditioned fear but does not change freezing induced by stimulation of the dorsal periaqueductal gray. Learn Mem 8: 164-169. doi: 10.1101/lm.36101
[52]	Seidenbecher T, Laxmi TR, Stork O, et al. (2003) Amygdalar and hippocampal theta rhythm synchronization during fear memory retrieval. Science 301: 846-850. doi: 10.1126/science.1085818
[53]	Arnsten AFT (2009) Stress signalling pathways that impair prefrontal cortex structure and function. Nat Rev Neurosci 10: 410-422. doi: 10.1038/nrn2648

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