Hemodynamic responses in amygdala and hippocampus distinguish between aversive and neutral cues during Pavlovian fear conditioning in behaving rats.

McHugh SB
Marques-Smith A
Li J
Rawlins JN
Lowry JP
Conway M
Gilmour G
Tricklebank MD
Bannerman DM
Scientific 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.


2013.Eur. J. Neurosci., 37(3):498-507.

Trouche S, Perestenko PV, van de Ven GM, Bratley CT, McNamara CG, Campo-Urriza N, Black SL, Reijmers LG, Dupret D

2016.Nat. Neurosci., 19(4):564-7.

Bocchio M, Fucsina G, Oikonomidis L, McHugh SB, Bannerman DM, Sharp T, Capogna M
2015.Neuropsychopharmacology, 40(13):3015-26.
Koolschijn RS, Emir UE, Pantelides AC, Nili H, Behrens TE, Barron HC
2019. Neuron 101:528-541
Trouche S, Koren V, Doig NM, Ellender TJ, El-Gaby M, Lopes-Dos-Santos V, Reeve HM, Perestenko PV, Garas FN, Magill PJ, Sharott A, Dupret D

2019. Cell, 176(6):1393-1406.e16.

Sloan M, Alegre-Abarrategui J, Potgieter D, Kaufmann AK, Exley R, Deltheil T, Threlfell S, Connor-Robson N, Brimblecombe KR, Wallings R, Cioroch M, Bannerman DM, Bolam JP, Magill PJ, Cragg SJ, Dodson PD, Wade-Martins R
2016.Hum. Mol. Genet., 25(5):951-63.