receptor-dependent long-term potentiation

I hope my NMDA receptors were working well in the 1980s as I try to recall the events leading up to the establishment of the mechanism of induction of LTP. My story begins in 1980 as I start my first postdoctoral position in the laboratory of Hugh McLennan, in Vancouver. Hugh was interested in l-glutamate as a neurotransmitter in the brain and was one of the pioneers in the identification of multiple classes of glutamate receptor. His PhD student, Stephen Kehl, was studying the actions of l-glutamate on CA1 neurons in the hippocampal slice preparation, when I arrived looking for a project. At that time also, a visitor to Hugh’s laboratory, David West, was working on LTP in this slice preparation. When I first saw LTP demonstrated by David, I was hooked and decided to spend the next two years working on this fascinating process. I was already well aware of the existence of multiple types of glutamate receptor, having spent a PhD in London studying with another major player in the glutamate field—John Davies. I asked myself the question whether different subtypes of glutamate receptor may be involved in the mediation of synaptic transmission and the induction of LTP; and this, with Hugh’s approval, is what I set out to investigate. There was no a priori reason to suspect one type of glutamate receptor over another with respect to a specific role in synaptic plasticity. I therefore decided to investigate the subtypes in a random order. The first agonist I found in the freezer was kainate. In my first experiment I found that a brief focal application of kainate induced a pronounced, long-lasting facilitation of the population spike recorded from the CA1 cell body region (Collingridge & McLennan 1981). Although this effect superficially resembled LTP it was immediately evident that kainate was not inducing LTP since the potentiation was associated with a sustained