Loss of BDNF or its receptors in three mouse models has unpredictable consequences for anxiety and fear acquisition
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Updated: May 8, 2026
Elevated Plus Maze for Mice
Published on: December 22, 2008
Ditte Olsen1, Mathias Kaas, Ole Schwartz
1The Lundbeck Foundation Research Centre, MIND, Danish Research Institute of Translational Neuroscience DANDRITE, Nordic EMBL Partnership, Department of Biomedicine, Aarhus University, DK-8000C Aarhus, Denmark.
Abstract:
BDNF-induced signaling is essential for the development of the central nervous system and critical for plasticity in adults. Mature BDNF signals through TrkB, while its precursor proBDNF employs p75(NTR), resulting in activation of signaling cascades with opposite effects on neuronal survival, growth cone decisions, and synaptic plasticity. Accordingly, variations in the genes encoding BDNF and its receptors sometimes have opposing influences in psychiatric disorders, and despite the vast literature, consensus is lacking about the behavioral consequences of disrupting the activity of the BDNF system in mice. To dissect the behavioral traits affected by dysfunctional BDNF/TrkB vs. proBDNF/p75(NTR) activity, we studied Bdnf(+/-), Ntrk2(+/-), and Ngfr(-/-) mice in parallel with respect to exploratory behavior, anxiety, startle, and fear acquisition. Our data reveal that the effect of proBDNF/BDNF and its receptors on behavior is more complex than expected. Strikingly, receptor-deficient mice displayed increased risk-taking behavior in the open field and elevated plus maze, whereas lack of proBDNF/BDNF had the opposite effect on mouse behavior. On the other hand, although TrkB signaling is instrumental for acquisition of fear memory in an inhibitory avoidance experiment, lack of p75(NTR) or proBDNF/BDNF conferred increased memory in this task. Importantly, none of the genotypes displayed any deficits in startle reflex, indicating unimpaired response to shock. The combined data illustrate an apparent paradox in the role of the BDNF system in controlling complex behavior and suggest that the individual components may also engage independently in separate signaling pathways.
Insights
Brain-Derived Neurotrophic Factor (BDNF) signaling impacts brain development and adult plasticity. This study reveals complex, opposing behavioral effects between BDNF/TrkB and proBDNF/p75(NTR) pathways in mice.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Genetics
Background:
- Brain-Derived Neurotrophic Factor (BDNF) signaling is crucial for central nervous system development and adult neural plasticity.
- Mature BDNF (via TrkB) and proBDNF (via p75(NTR)) activate distinct signaling cascades with opposing effects on neuronal functions.
- Genetic variations in BDNF and its receptors are linked to psychiatric disorders, but their precise behavioral consequences remain debated.
Purpose of the Study:
- To investigate the distinct behavioral effects of dysfunctional BDNF/TrkB versus proBDNF/p75(NTR) signaling pathways.
- To analyze exploratory behavior, anxiety, startle response, and fear acquisition in genetically modified mouse models.
Main Methods:
- Comparative analysis of behavior in mice with genetic modifications affecting BDNF, TrkB (Ntrk2), and p75(NTR) (Ngfr).
- Assessment of risk-taking behavior using the open field and elevated plus maze tests.
- Evaluation of fear memory acquisition via an inhibitory avoidance task and startle reflex measurement.
Main Results:
- Mice lacking BDNF receptors (TrkB or p75(NTR)) exhibited increased risk-taking, contrasting with mice lacking BDNF, which showed reduced risk-taking.
- TrkB signaling impairment hindered fear memory acquisition, while p75(NTR) or BDNF deficiency enhanced it.
- No genotype displayed deficits in the startle reflex, indicating intact sensory-motor gating.
Conclusions:
- The BDNF system's role in complex behaviors is intricate, presenting paradoxical findings.
- Distinct components of the BDNF system may operate through independent signaling pathways to modulate behavior.
- Further research is needed to fully elucidate the independent and interactive roles of BDNF/TrkB and proBDNF/p75(NTR) signaling in neurobiology.
