McHugh, Stephen B. and Marques-Smith, Andre and Li, Jennifer and Rawlins, J.N.P. and Lowry, John P. and Conway, Michael W. and Gilmour, Gary and Tricklebank, Mark and Bannerman, David M. (2013) Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats. European Journal of Neuroscience, 37. pp. 498-507. ISSN 0953-816X

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Abstract

Lesion and electrophysiological studies in rodents have identified the amygdala and hippocampus (HPC) as key structures for Pavlovian fear conditioning, but human functional neuroimaging studies have not consistently found activation of these structures. This could be because hemodynamic responses cannot detect the sparse neuronal activity proposed to underlie conditioned fear. Alternatively, differences in experimental design or fear levels could account for the discrepant findings between rodents and humans. To help distinguish between these alternatives, we used tissue oxygen amperometry to record hemodynamic responses from the basolateral amygdala (BLA), dorsal HPC (dHPC) and ventral HPC (vHPC) in freely-moving rats during the acquisition and extinction of conditioned fear. To enable specific comparison with human studies we used a discriminative paradigm, with one auditory cue [conditioned stimulus (CS)+] that was always followed by footshock, and another auditory cue (CS-) that was never followed by footshock. BLA tissue oxygen signals were significantly higher during CS+ than CS- trials during training and early extinction. In contrast, they were lower during CS+ than CS- trials by the end of extinction. dHPC and vHPC tissue oxygen signals were significantly lower during CS+ than CS- trials throughout extinction. Thus, hemodynamic signals in the amygdala and HPC can detect the different patterns of neuronal activity evoked by threatening vs. neutral stimuli during fear conditioning. Discrepant neuroimaging findings may be due to differences in experimental design and/or fear levels evoked in participants. Our methodology offers a way to improve translation between rodent models and human neuroimaging.

Item Type:	Article
Additional Information:	The definitive version of this article is available at DOI: 10.1111/ejn.12057
Keywords:	amygdala; extinction; fear; functional magnetic resonance imaging; hippocampus; tissue oxygen;
Academic Unit:	Faculty of Science and Engineering > Chemistry
Item ID:	7006
Identification Number:	https://doi.org/10.1111/ejn.12057
Depositing User:	John Lowry
Date Deposited:	03 Mar 2016 15:58
Journal or Publication Title:	European Journal of Neuroscience
Publisher:	Blackwell Publishing Ltd
Refereed:	Yes
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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