Long-term-potentiation and memory. Where do we stand?

Question

I was reading the answers to the question: How and where, in the human brain, are memories stored? and, as expected, LTP and LTD came out.

Every time I read about LTP/LTD there is always something that bugs me a lot.

When I read papers about LTP/LTD (OK, I should really say "when I browse", as I'm not exactly in that area of neurosciences, and that is probably the reason why I am confused by this) I always see these very neat experiments where stimulating a neuron in a certain way increases/decreases its further responses. Then, I look at the time axes on the graphs, or read the Methods, and I see that the LTP was induced and analysed few minutes after the stimulus.

So my questions are:

1. Is there clear evidence that LTP is involved in long-term memory (not counting 1 hour as long-term...)?
2. Has LTP/LTD been shown in vivo after long period of time (e.g. months).
3. For those who work in the field, is there a strong belief that LTP/LTD are the only phenomena underlying memory?

Answer 1

Is there clear evidence that LTP is involved in long-term memory (not counting 1 hour as long-term...)? Has LTP/LTD been shown in vivo after long period of time (e.g. months).

This Journal of Neuroscience paper shows LTP in vivo measured out to one year: Abraham WC, Logan B, Greenwood JM, Dragunow M. 2002. Induction and experience-dependent consolidation of stable long-term potentiation lasting months in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 22: 9626–34.

Answer 2

Really good questions. As the guy who brought up LTP/LTD in the question you referenced, I thought I would weigh in.

There is the traditional definition of LTP/LTD as an increased/decreased synaptic efficacy at a single synapse or in a single cell. As you've noted, this is unlikely to be the only phenomena underlying memory and sometimes it's hard to see how some of these mechanisms can result in memory on behavioral timescales.

Let me propose, therefore, that the term long-term plasticity is more relevant these days, as it can refer to a variety of mechanisms that relate to the ability of the nervous system to change in stable ways over time. Physiological mechanisms involving changes in protein expression include traditional LTP/LTD at single synapses, but also homeostatic plasticity and long-term changes in intrinsic excitability where the tendency of the cell to fire changes independent of changes in synaptic weighting. Some structural mechanisms include the growth of new synapses, new spines, and new neurons--synaptogenesis, spinogenesis, and neurogenesis.

In the end, it is all of these mechanisms (and probably more) at play. Note, for instance, that the plasticity may move through structural changes in the system. This means that the lifetime of LTP in one cell or at one synapse does not necessarily have to be the same as the lifetime of the memory itself. All that said, I think all plasticity mechanisms ultimately reduce down to a change in the ability of an input to elicit an action potential somewhere in the brain (known as EPSP-spike coupling). This is likely to be the basic underlying mechanism of memory.

Answer 3

Good questions. I don't think that LTP has been (or will be) shown to be THE mechanism for long term memory. It is one of many mechanisms, all with different time courses, that contribute to the modification of synaptic efficiencies.

One mechanism not mentioned much anymore, but which I feel is absolutely crucial, is dendritic spine growth. Spines are malleable and formation/destruction of spines is probably very related to long term memory. But as always, the full picture is going to be a combination of mechanisms.

Here is a paper to have a look at: Engert F, Bonhoeffer T. 1999. Dendritic spine changes associated with hippocampal long-term synaptic plasticity. Nature 399: 66–70.