Interconnected neural networks representing BDNF and TrkB signaling.

Unlocking Brain Plasticity: How BDNF and TrkB Rewrite Neural Connections

Kai Mendoza in Science & Nature August 2025 • 4 min read.

"Discover how brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, orchestrate crucial communication pathways in your brain, paving the way for enhanced learning and memory."

The human brain, a marvel of biological engineering, possesses an extraordinary ability to adapt and reorganize itself throughout life. This capacity, known as neuroplasticity, allows us to learn new skills, form memories, and recover from injuries. At the heart of this intricate process lies a powerful molecule called brain-derived neurotrophic factor, or BDNF.

BDNF acts like a fertilizer for your brain, promoting the growth, survival, and differentiation of neurons. It exerts its influence by binding to a high-affinity receptor called TrkB, triggering a cascade of intracellular signaling pathways that ultimately shape the structure and function of neural circuits. While scientists have long recognized the importance of BDNF and TrkB in learning and memory, the precise mechanisms by which they orchestrate these complex processes remain a subject of intense investigation.

Now, a compelling new study sheds light on how BDNF and TrkB modulate the activity of NMDA receptors (NMDARs), key players in excitatory neurotransmission and synaptic plasticity. By dynamically interacting with a signaling molecule called RasGrf1, BDNF and TrkB fine-tune NMDAR signaling, influencing the balance between long-term potentiation (LTP) and long-term depression (LTD) – two fundamental processes underlying learning and memory.

BDNF and TrkB: Orchestrating Neural Communication

Interconnected neural networks representing BDNF and TrkB signaling.

The study, conducted by Talebian, Robinson-Brookes, and Meakin (2018), unveils a novel mechanism by which BDNF and TrkB modulate NMDAR signaling, offering insights into how these molecules influence learning, memory, and overall brain health. The researchers focused on RasGrf1, a guanine nucleotide exchange factor known to interact with both Ras and Rac – two key signaling molecules involved in neuronal growth and plasticity.

The researchers discovered that NMDA stimulation recruits RasGrf1 to the NR2B subunit of the NMDAR, a process associated with LTD. However, co-stimulation with BDNF uncouples this association, recruiting RasGrf1 to TrkB instead. This dynamic interplay suggests that BDNF and TrkB actively reshape NMDAR signaling by redirecting RasGrf1 to different cellular compartments.

Uncoupling LTD: BDNF helps detach RasGrf1 from NR2B, reducing signals that cause long-term depression in synapses.
Promoting Growth: It encourages RasGrf1 to join with TrkB, boosting neuron growth and enhancing learning and memory processes.
Dual Action: This dual mechanism allows TrkB to fine-tune NMDA receptor functions, balancing brain activities for learning and growth.

Further experiments revealed that BDNF stimulates the tyrosine phosphorylation of RasGrf1, a modification known to enhance neurite outgrowth. Additionally, BDNF promotes the tyrosine phosphorylation of NR2B, a process that increases NMDAR cell surface retention. These findings highlight the multifaceted effects of BDNF and TrkB on NMDAR signaling, demonstrating how these molecules dynamically regulate synaptic function and neuronal growth.

Rewriting the Brain's Code: Implications and Future Directions

These findings have significant implications for our understanding of neuroplasticity, cognitive enhancement, and the treatment of neurological disorders. By unraveling the intricate mechanisms by which BDNF and TrkB modulate NMDAR signaling, scientists may be able to develop novel therapies to promote learning, memory, and recovery from brain injuries.

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Everything You Need To Know

What is BDNF, and why is it important for my brain?

Brain-derived neurotrophic factor, or BDNF, is a protein that supports the growth, survival, and specialization of neurons in the brain. It's crucial because it acts like a fertilizer, promoting the health and development of brain cells. Without sufficient BDNF, the brain's ability to adapt and learn is significantly diminished. Reduced levels of BDNF have been linked to various neurological disorders, highlighting its importance for overall brain health and function.

What is TrkB, and how does it relate to BDNF?

TrkB is a receptor on the surface of neurons that binds to BDNF. This binding initiates a series of intracellular signaling pathways that are essential for neuroplasticity, learning, and memory. The interaction between BDNF and TrkB is significant because it directly influences the structure and function of neural circuits. Without TrkB, BDNF cannot exert its effects on neurons, which underscores TrkB's vital role in mediating the beneficial effects of BDNF on brain function.

What are NMDA receptors, and what role do they play in my brain?

NMDA receptors, or NMDARs, are key players in excitatory neurotransmission and synaptic plasticity. They are critical for learning and memory because they mediate the strengthening of synaptic connections in response to neural activity. The modulation of NMDAR signaling by BDNF and TrkB influences the balance between long-term potentiation (LTP) and long-term depression (LTD), which are fundamental processes underlying learning and memory. Dysregulation of NMDAR function is implicated in various neurological and psychiatric disorders, making their proper function essential for brain health.

What is RasGrf1, and how does it connect to BDNF and TrkB?

RasGrf1 is a signaling molecule known to interact with both Ras and Rac, which are key signaling molecules involved in neuronal growth and plasticity. It is involved in neuronal communication. The dynamic interplay between BDNF, TrkB, and RasGrf1 is significant because it allows for fine-tuning of NMDA receptor functions, influencing the balance between long-term potentiation (LTP) and long-term depression (LTD). This balance is crucial for learning and memory processes. Understanding how RasGrf1 mediates these interactions could lead to new therapies for cognitive enhancement and neurological disorders.

What are long-term potentiation and long-term depression, and why are they important?

Long-term potentiation (LTP) and long-term depression (LTD) are two fundamental processes underlying learning and memory. LTP strengthens synaptic connections, making it easier for neurons to communicate, while LTD weakens synaptic connections. The balance between LTP and LTD is crucial for neuroplasticity and the ability of the brain to adapt and learn. BDNF and TrkB play a critical role in modulating this balance by influencing NMDA receptor signaling. Disruptions in LTP and LTD have been implicated in various neurological and psychiatric disorders, highlighting their importance for brain health.