Hippocampal ripples and memory consolidation

So the vos Savant post got me thinking... I'm kind of comfortable talking about sleep (or at least, comfortable enough to get in trouble, I'm sure), and would love to make a few more posts on it. And, hey, why the hell not? I'm sure some of my friends would like to see what I read, and why not start making occasional research posts out of it? Who knows; if even one or two readers get something out of it, this whole thing is definitely worthwhile. If not, at least I get to work things out myself.

So, I present one of my favorite papers in recent history:

Girardeau, G., Benchenane, K., Wiener, S., Buzsáki, G., & Zugaro, M. (2009). Selective suppression of hippocampal ripples impairs spatial memory Nature Neuroscience, 12 (10), 1222-1223 DOI: 10.1038/nn.2384

It's a short, short paper, with an online supplement; a lot of publications in the glamour journals are shorter than I feel they should be, because there's a lot of backstory that this article could go into. However, all the relevant citations are there, and I can at least do a quick zip through those. There's a really nice narrative to all this, I promise.

So let's start WAAAAY back in the 1980s. Gregory Buszaki was working away in his lab on memory consolidation and saw these little ripple events from electrode recordings in mice during sleep. In a 1989 commentary piece, he laid out his theory in full. The short version: exploratory (mostly waking) behavior saw certain activation patterns in pyramidal cells in the CA3 region. During quiescence and slow wave sleep, sharp-wave ripples, or population bursts, in the pyramidal cells of the CA3 region of the hippocampus were potentiating post-synaptic regions in the CA1 region; in more plain-speak, the CA1 neurons, which were active in exploration, were now "priming" the CA3 neurons.



(See the mousey hippocampus. See it SPIKE! Original image from the Buszaki 1988 paper.)

I'm probably doing a minor disservice to summarize Buszaki's model that shortly (it's a great big 20 page paper, after all, and a wonderful one at that; if you're big into the neuroscience of memory, it's a must-read), but the narrative must continue! We've still got a few stops in history to make.

So, moving right along, we go to William Skaggs in 2007. He was looking for the same thing in macaques. The catch? Well... their brains are a little bit bigger than mouse brains, so getting deep brain recordings is usually a challenge. Having not worked with primates before, I can only sympathize with the sort of difficulties they pose. Noisy data, few subjects, and generally undisciplined behavior... all seen in this paper. But he got the same spikes in the same region, spiking on rest behavior after a memory intensive task. The article doesn't show much except "Oh, we see the same in primates! Awesome!"

And step up another year to 2008, a paper by Nikolai Axmacher. We have humans this time!

Now, we can't exactly throw electrodes into deep-brain areas of humans for purely experimental reasons - his participants were epileptic patients, and his recordings were from electrodes implanted for therapeutic purposes. Further, the fact that we saw them in humans had been established, but he took it a step further. He had participants doing a visual memory task - Show participants a series of pictures, let them rest for an hour (preferably napping) while recording, then show them old pictures mixed with new. "Is this new or old?" Record correct answers.

So what did he find? The more sharp-wave ripples he saw, the better that person performed on the new/old task. This sort of thing had been measured in rats back in Buszaki's lab, but to find that the same observation held for humans? Woohoo!

And now back to mice. See, all the prior studies have a minor flaw from a strictly empiricist standpoint - they were all purely correlative. Sure, we can match how many of these show to an increase in performance... but there's nothing selective about that. It could be a side-effect of something upstream, perhaps.

So NOW we're to the Girardeau paper. Girardeau's team used a radial arm maze, three times a day with three baited arms. Rats were given either until they got all three correct arms or time was up, then after the training period were put in a flowerpot in the middle of the maze to rest for an hour.

(See, I wasn't kidding about the flowerpot.)

Now, for the really cool part: Girardeau's team had a method of suppressing the synchronous neuronal firing of the sharp wave ripples. Delivering a small shock to the relevant area disrupted the ripple-events, and didn't otherwise disturb the little whiskered ones! So there were three groups - one didn't even have have any shocks delivered, one group delivered shocks when ripples were observed (suppressing ripples), and one group had a delayed shock (giving shocks, but conserving ripple events). The latter two are shown in the above figure. This was during that one hour period following training.



And what did Girardeau's team find? EXACTLY what Buszaki's model twenty years ago would have predicted. The no-shock and delay-shock little ones performed exactly the same being re-tested in the maze; the disrupting-shock/ripple-suppressed group performed worse, with more errors. And keep in mind, these ripple events weren't disrupted for all sleep, just one hour following training. And sleep architecture (the large-scale electrical patterns associated with sleep and sleep stages) was conserved even in the ripple-suppressed group, so it wasn't any change in the sleep architecture, either! Girardeau's team is pretty thorough on covering bases, with the checks on sleep architecture, checking that motion wasn't stereotyped (in other words, establishing spatial rather than motor memory as the "strategy" used by the rats).

I can't even imagine how that must have been for Buszaki, to see his model play out so beautifully. The whole narrative picture here I've actually doubted at times, because it plays out too well. Getting a picture that pretty is usually a Bad Thing - someone's fudging something somewhere. Sometimes, though, it does happen, as it seems to have done so here.



Sources:
Axmacher, N., Elger, C., & Fell, J. (2008). Ripples in the medial temporal lobe are relevant for human memory consolidation Brain, 131 (7), 1806-1817 DOI: 10.1093/brain/awn103

BUZSAKI, G. (1989). Two-stage model of memory trace formation: A role for “noisy” brain states Neuroscience, 31 (3), 551-570 DOI: 10.1016/0306-4522(89)90423-5

Girardeau, G., Benchenane, K., Wiener, S., Buzsáki, G., & Zugaro, M. (2009). Selective suppression of hippocampal ripples impairs spatial memory Nature Neuroscience, 12 (10), 1222-1223 DOI: 10.1038/nn.2384

Skaggs, W., McNaughton, B., Permenter, M., Archibeque, M., Vogt, J., Amaral, D., & Barnes, C. (2007). EEG Sharp Waves and Sparse Ensemble Unit Activity in the Macaque Hippocampus Journal of Neurophysiology, 98 (2), 898-910 DOI: 10.1152/jn.00401.2007