The role of brain derived neurotrophic factor in learned fear processing: an awake rat fMRI study

Harris, A. P., Lennen, R. J., Brydges, Nichola, Jansen, M. A., Pernet, C. R., Whalley, H. C., Marshall, I., Baker, S., Basso, A. M., Day, M., Holmes, M. C. and Hall, Judith Elizabeth ORCID: https://orcid.org/0000-0002-6770-7372 2016. The role of brain derived neurotrophic factor in learned fear processing: an awake rat fMRI study. Genes, Brain and Behavior 15 (2) , pp. 221-230. 10.1111/gbb.12277

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Abstract

Brain-derived neurotrophic factor (BDNF) signaling is implicated in the aetiology of many psychiatric disorders associated with altered emotional processing. Altered peripheral (plasma) BDNF levels have been proposed as a biomarker for neuropsychiatric disease risk in humans. However the relationship between peripheral and central BDNF levels and emotional brain activation is unknown. We used heterozygous BDNF knockdown rats (BDNF+/- ) to examine the effects of genetic variation in the BDNF gene on peripheral and central BDNF levels and emotional brain activation as assessed by awake fMRI. BDNF+/- and control rats were trained to associate a flashing light (conditioned stimulus; CS) with foot-shock, and brain activation in response to the CS was measured 24h later in awake rats using fMRI. Central and peripheral BDNF levels were decreased in BDNF+/- rats compared to control rats. Activation of fear circuitry (amygdala, periaqueductal gray, granular insular) was seen in control animals, however activation of this circuitry was absent in BDNF+/- animals. Behavioral experiments confirmed impaired conditioned fear responses in BDNF+/- rats, despite intact innate fear responses. These data confirm a positive correlation (r = 0.86, 95% CI [0.55, 0.96]; P = 0.0004) between peripheral and central BDNF levels and indicate a functional relationship between BDNF levels and emotional brain activation as assessed by fMRI. The results demonstrate the use of rodent fMRI as a sensitive tool for measuring brain function in preclinical translational studies using genetically modified rats and support the use of peripheral BDNF as a biomarker of central affective processing.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Amygdala; awake rat fMRI; BDNF; Pavlovian conditioning; transgenic rat
Publisher:	Wiley-Blackwell
ISSN:	1601-1848
Funders:	AbbVie, CCACE, BHF CoRE, Wellcome Trust Strategic Award. Grant Number: 503147, MRC Centre Grant. Grant Number: G0800509, BBSRC, MRC, NMHRI
Date of Acceptance:	17 November 2015
Last Modified:	31 Oct 2022 10:45
URI:	https://orca.cardiff.ac.uk/id/eprint/86046

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