Long-term potentiation, or LTP, is a process by which connections between neurons become stronger with frequent activation. LTP is thought to be a way in which the brain changes in response to experience, and thus may be an mechanism underlying learning and memory. In this video, I discuss one type of LTP: NMDA-receptor dependent LTP. I outline the mechanism underlying NMDA-receptor LTP and describe how it is thought to strengthen synaptic connections where it occurs.
TRANSCRIPT:
Welcome to 2 minute neuroscience, where I simplistically explain neuroscience topics in 2 minutes or less. In this installment I will discuss long-term potentiation, or LTP.
LTP is a process by which synaptic connections between neurons become stronger with frequent activation. LTP is thought to be a way in which the brain changes in response to experience, and thus may be an mechanism underlying learning and memory.
There are a number of ways in which LTP can occur. The best-known mechanism involves a glutamate receptor known as the NMDA receptor. In NMDA-receptor dependent LTP, glutamate release first activates a subtype of glutamate receptor known as the AMPA receptor. NMDA receptors are found nearby these AMPA receptors, but are not activated by low levels of glutamate release because the ion channel of an NMDA receptor is blocked by a magnesium ion. If frequent action potentials cause greater stimulation of AMPA receptors, however, this will cause the postsynaptic neuron to depolarize,
which eventually causes the voltage-dependent magnesium blockage of the NMDA receptor to be removed, allowing calcium ions to flow in through the NMDA receptor. This influx of calcium initiates cellular mechanisms that cause more AMPA receptors to be inserted into the neuron’s membrane. The new AMPA receptors are also more responsive to glutamate, and allow more positively charged ions to enter the cell when activated.
Now, the postsynaptic cell is more sensitive to glutamate because it has more receptors to respond to it. Additionally, there are thought to be signals that travel back across the synapse to stimulate greater levels of glutamate release. All of this makes the synapse stronger and more likely to be activated in the future.
This process is also associated with changes in gene transcription in the neuron, which can lead to the production of new receptors or modifications to the structure of the cell. These changes seem to be important for making the increased responsiveness of LTP long-lasting.
REFERENCES:
Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science. 5th ed. New York. McGraw-Hill; 2013.
