Investigative Magnetic Resonance Imaging

Korean Society of Magnetic Resonance in Medicine (대한자기공명의과학회)
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Manganese-Enhanced MRI Reveals Brain Circuits Associated with Olfactory Fear Conditioning by Nasal Delivery of Manganese

  • Yang, Ji-ung (Department of Medical & Biological Engineering, Kyungpook National University) ;
  • Chang, Yongmin (Department of Medical & Biological Engineering, Kyungpook National University) ;
  • Lee, Taekwan (Korea Brain Research Institute)
  • Received : 2021.10.22
  • Accepted : 2022.02.03
  • Published : 2022.07.01
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Abstract

Purpose: The survival of organisms critically depends on avoidance responses to life-threatening stimuli. Information about dangerous situations needs to be remembered to produce defensive behavior. To investigate underlying brain regions to process information of danger, manganese-enhanced MRI (MEMRI) was used in olfactory fear-conditioned rats. Materials and Methods: Fear conditioning was conducted in male Sprague-Dawley rats. The animals received nasal injections of manganese chloride solution to monitor brain activation for olfactory information processing. Twenty-four hours after manganese injection, rats were exposed to electric foot shocks with odor cue for one hour. Control rats were exposed to the same odor cue without foot shocks. Forty-eight hours after the conditioning, rats were anesthetized and their brains were scanned with 9.4T MRI. Acquired images were processed and statistical analyses were performed using AFNI. Results: Manganese injection enhanced brain areas involved in olfactory information pathways in T1 weighted images. Rats that received foot shocks showed higher brain activation in the central nucleus of the amygdala, septum, primary motor cortex, and preoptic area. In contrast, control rats displayed greater signals in the orbital cortex and nucleus accumbens. Conclusion: Nasal delivery of manganese solution enhanced olfactory signal pathways in rats. Odor cue paired with foot shocks activated amygdala, the central brain region in fear, and related brain circuits. Use of MEMRI in fear conditioning provides a reliable monitoring technique of brain activation for fear learning.

Keywords

Acknowledgement

This research was supported by the R&D fund by the Ministry of Health and Welfare [grant number HI13C1015], the basic research program through the Korean Brain Research Institute, funded by the Ministry of Science and Information Communications Technology (ICT) (21- BR-05-01) and by the molecular MR study group of KSMRM (2021).

References

  1. Dunsmoor JE, Paz R. Fear generalization and anxiety: behavioral and neural mechanisms. Biol Psychiatry 2015;78:336-343 https://doi.org/10.1016/j.biopsych.2015.04.010
  2. Johansen JP, Cain CK, Ostroff LE, LeDoux JE. Molecular mechanisms of fear learning and memory. Cell 2011;147:509-524 https://doi.org/10.1016/j.cell.2011.10.009
  3. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000;23:155-184 https://doi.org/10.1146/annurev.neuro.23.1.155
  4. Pautler RG. In vivo, trans-synaptic tract-tracing utilizing manganese-enhanced magnetic resonance imaging (MEMRI). NMR Biomed 2004;17:595-601 https://doi.org/10.1002/nbm.942
  5. Yu X, Wadghiri YZ, Sanes DH, Turnbull DH. In vivo auditory brain mapping in mice with Mn-enhanced MRI. Nat Neurosci 2005;8:961-968 https://doi.org/10.1038/nn1477
  6. Silva AC, Lee JH, Wu CW, et al. Detection of cortical laminar architecture using manganese-enhanced MRI. J Neurosci Methods 2008;167:246-257 https://doi.org/10.1016/j.jneumeth.2007.08.020
  7. Watanabe T, Natt O, Boretius S, Frahm J, Michaelis T. In vivo 3D MRI staining of mouse brain after subcutaneous application of MnCl2. Magn Reson Med 2002;48:852-859 https://doi.org/10.1002/mrm.10276
  8. Chan KC, Fu QL, Hui ES, So KF, Wu EX. Evaluation of the retina and optic nerve in a rat model of chronic glaucoma using in vivo manganese-enhanced magnetic resonance imaging. Neuroimage 2008;40:1166-1174 https://doi.org/10.1016/j.neuroimage.2008.01.002
  9. Pautler RG, Koretsky AP. Tracing odor-induced activation in the olfactory bulbs of mice using manganese-enhanced magnetic resonance imaging. Neuroimage 2002;16:441-448 https://doi.org/10.1006/nimg.2002.1075
  10. Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 1996;29:162-173 https://doi.org/10.1006/cbmr.1996.0014
  11. Jenkinson M, Beckmann CF, Behrens TE, Woolrich MW, Smith SM. Fsl. Neuroimage 2012;62:782-790 https://doi.org/10.1016/j.neuroimage.2011.09.015
  12. Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 5th ed. New York: Academic Press, 2005
  13. Pautler RG, Silva AC, Koretsky AP. In vivo neuronal tract tracing using manganese-enhanced magnetic resonance imaging. Magn Reson Med 1998;40:740-748 https://doi.org/10.1002/mrm.1910400515
  14. Mori K, Manabe H, Narikiyo K, Onisawa N. Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex. Front Psychol 2013;4:743 https://doi.org/10.3389/fpsyg.2013.00743
  15. Imai T. Construction of functional neuronal circuitry in the olfactory bulb. Semin Cell Dev Biol 2014;35:180-188 https://doi.org/10.1016/j.semcdb.2014.07.012
  16. Kita H, Kitai ST. Amygdaloid projections to the frontal cortex and the striatum in the rat. J Comp Neurol 1990;298:40-49 https://doi.org/10.1002/cne.902980104
  17. 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 https://doi.org/10.1111/ejn.12610
  18. Kuniishi H, Yamada D, Wada K, Yamada M, Sekiguchi M. Stress induces insertion of calcium-permeable AMPA receptors in the OFC-BLA synapse and modulates emotional behaviours in mice. Transl Psychiatry 2020;10:154 https://doi.org/10.1038/s41398-020-0837-3
  19. Shen CJ, Zheng D, Li KX, et al. Cannabinoid CB1 receptors in the amygdalar cholecystokinin glutamatergic afferents to nucleus accumbens modulate depressive-like behavior. Nat Med 2019;25:337-349 https://doi.org/10.1038/s41591-018-0299-9
  20. Chang CH, Grace AA. Amygdala-ventral pallidum pathway decreases dopamine activity after chronic mild stress in rats. Biol Psychiatry 2014;76:223-230 https://doi.org/10.1016/j.biopsych.2013.09.020
  21. Bangasser DA, Lee CS, Cook PA, Gee JC, Bhatnagar S, Valentino RJ. Manganese-enhanced magnetic resonance imaging (MEMRI) reveals brain circuitry involved in responding to an acute novel stress in rats with a history of repeated social stress. Physiol Behav 2013;122:228-236 https://doi.org/10.1016/j.physbeh.2013.04.008
  22. Zhang GW, Shen L, Tao C, et al. Medial preoptic area antagonistically mediates stress-induced anxiety and parental behavior. Nat Neurosci 2021;24:516-528 https://doi.org/10.1038/s41593-020-00784-3
  23. Jeong KY, Lee C, Cho JH, Kang JH, Na HS. New method of manganese-enhanced magnetic resonance imaging (MEMRI) for rat brain research. Exp Anim 2012;61:157-164 https://doi.org/10.1538/expanim.61.157
  24. Inui T, Inui-Yamamoto C, Yoshioka Y, Ohzawa I, Shimura T. Activation of efferents from the basolateral amygdala during the retrieval of conditioned taste aversion. Neurobiol Learn Mem 2013;106:210-220 https://doi.org/10.1016/j.nlm.2013.09.003
  25. Devonshire IM, Burston JJ, Xu L, et al. Manganese-enhanced magnetic resonance imaging depicts brain activity in models of acute and chronic pain: a new window to study experimental spontaneous pain? Neuroimage 2017;157:500-510 https://doi.org/10.1016/j.neuroimage.2017.06.034