The Brain Prize, a thing I don’t think I knew existed, just gave $1,000,000 to three neuroscientists for their work on LTP. As with most prizes, the best part is the motivation to go back and read classic papers!
The best winner was Richard Morris because he kind of revolutionized the memory field with this figure:
Yes, he created the Morris Water Maze, used to study learning and memory in a seemingly-infinite number of papers.
When was the last time you went back and actually read the original Morris Water Maze paper? I know I had not ever read it before today: but I should have.
No less important was the work of Timothy Bliss (and Terje Lomo, who did not win) illustrating the induction of LTP. Most of us have probably heard “neurons that fire together, wire together” and this is the first real illustration of the phenomenon (in 1973):
Bliss and Lomo were able to induce long-lasting changes in the strength of connections between two neurons by a “tetanic stimulation protocol“. The above figure is seared into my brain from my first year of graduate school, where Jeff Isaacson dragged us through paper after paper that used variations on this protocol to investigate the properties of LTP.
The final winner was Graham Collingridge who demonstrated that hippocampal LTP was induced via NMDA receptors. I don’t think this was the paper that demonstrated it, but I always found his 1986 paper on slow NMDA receptors quite beautiful:
Here, he has blocked NMDA receptors with APV and sees no spiking after repeated stimulation. However, when this blocker is washed out, you see spiking only after receiving several inputs because of the slow timescale of the receptors.
While historically powerful, the focus on NMDA receptors can be misleading. LTP can be induced in many different ways depending on the specific neural type and brain region! For my money, I have always been a fan of the more generalized form, STDP. Every neuroscientist should read and understand the Markram et al (1997) paper that demonstrates it and the Bi and Poo (1998) paper that has this gorgeous figure:
Read about the past, and remember where your science came from.