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Investigating the Role of Hippocampal BDNF in Anxiety Vulnerability Using Classical Eyeblink Conditioning
Kellie L Janke1, Tara P Cominski2, Eldo V Kuzhikandathil3
1Research Service, Neurobehavioral Research Laboratory, VA New Jersey Heath Care System , East Orange, NJ , USA ; Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers Biomedical and Health Sciences , Newark, NJ , USA.
Brain-derived neurotrophic factor (BDNF) impacts learning in Wistar-Kyoto rats, an animal model for behavioral inhibition. Reduced BDNF in these rats dampens their facilitated associative learning, suggesting a link to anxiety disorders.
Area of Science:
- Neuroscience
- Behavioral Science
- Genetics
Background:
- Anxiety disorders are linked to dysregulation of brain-derived neurotrophic factor (BDNF), behavioral inhibition (BI), and reduced hippocampal volume.
- Individuals with BI exhibit faster classical eyeblink conditioning (CCER) acquisition, a trait mirrored in Wistar-Kyoto (WKY) rats, an animal model of BI.
Purpose of the Study:
- To investigate the role of hippocampal BDNF in the enhanced delay CCER observed in WKY rats.
- To determine if manipulating hippocampal BDNF levels can alter CCER acquisition in WKY rats.
Main Methods:
- Compared CCER acquisition between Wistar-Kyoto (WKY) rats and Sprague Dawley (SD) rats.
- Measured BDNF, TrkB, and Arc mRNA levels in the dentate gyrus following learning.
- Administered bilateral BDNF or saline infusions into the dentate gyrus of WKY and SD rats before CCER training.
Main Results:
- WKY rats showed facilitated CCER acquisition compared to SD rats.
- SD rats exhibited increased BDNF and Arc mRNA in the dentate gyrus post-learning, while WKY rats showed smaller learning-induced increases.
- BDNF infusion into the WKY rat dentate gyrus dampened CCER acquisition, making it similar to SD rats; BDNF did not affect SD rat acquisition.
Conclusions:
- Inherent differences in the BDNF system are critical for the facilitated associative learning in WKY rats.
- Reduced hippocampal BDNF may underlie the enhanced learning in WKY rats and potentially individuals with BI.
- Facilitated associative learning could be a vulnerability factor for developing anxiety disorders.
