Investig Magn Reson Imaging.  2022 Jun;26(2):96-103. 10.13104/imri.2022.26.2.96.

Manganese-Enhanced MRI Reveals Brain Circuits Associated with Olfactory Fear Conditioning by Nasal Delivery of Manganese

Affiliations
  • 1Department of Medical & Biological Engineering, Kyungpook National University, Daegu, Korea
  • 2Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
  • 3Department of Radiology, Kyungpook National University Hospital, Daegu, Korea
  • 4Department of Molecular Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
  • 5Korea Brain Research Institute, Daegu, Korea

Abstract

Purpose
The survival of organisms critically depends on avoidance responses to lifethreatening 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. Fortyeight 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.

Keyword

Manganese MRI; Fear conditioning; Olfactory circuit
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