So, my theme is memory and forgetting.
And let me begin with a little story.
We live in Edinburgh, in Scotland, in the north of the country,
and I had to go, some years ago, on a business trip down to London,
in the middle of winter.
So I flew down, and I got on the train,
got close to London, got on the metro
and was headed for my destination.
And it was very warm on the metro, incredibly hot,
so I took off my winter coat and read the newspaper.
And when I got to Oxford Circus on the metro,
I got off the train to go to my meeting
and realized, just as the train was pulling out of the station,
that I’d left my coat on the train.
So I rushed up to the station staff and I explained what had happened.
And I asked them, would they ring forward
and ask a colleague if they could find my coat.
So I waited, and waited a while.
And then, the man came up to me and said,
“We’ve found your coat,
a very kind member of the public has handed it in,
and if you get back on the train and go to such and such a station,
you can get your coat again.”
So that was great.
So I got on the train, and I went to this station,
and I went up to the office, and just as I was about to get my coat,
I realized that I’d left my briefcase back in Oxford Circus.
(Laughter)
So I had to explain to the station staff,
would they phone back to the staff in Oxford Circus
and see if they could find my briefcase.
I heard the man say, (Spanish) “We have a madman here.”
(Laughter)
In broad London slang, you appreciate.
So I went back to Oxford Circus, gripping my coat tightly,
and I got there, and I was finally reunited,
not only with my coat, but my briefcase.
Now, the story actually goes on with even more embarassment.
But I think that’s enough for today (Laughter)
to explain that forgetting happens to us all.
It’s what my mum and dad would have called a fact of life.
And it’s annoying, isn’t it? When we forget something.
And it seems to get in the way.
But what I want to put to you today
is that forgetting is a perfectly normal part of memory.
In fact, it’s a necessary part of memory,
and I will try to explain this in terms of the way the brain forms memories
and the processes that are involved.
Now, we make memories all the time,
and there are situations, such as at school,
where the process of committing something to memory
is a very deliberate process, intentional,
we’re trying hard to, say, learn English
or in my case “español,”
and you really have to make an effort.
But most of the time,
the process of memory happens just automatically.
You can’t stop it.
Whatever you attend to, you form some representation,
not necessarily completely accurate,
but some representation of what’s happened to you.
So I think I could probably ask anybody in this room
what you had for breakfast today,
and you’d be able to tell me.
And so, there’s this sense
in which memory is happening completely automatically.
Now, the brain is clearly involved,
it has a number of different memory systems,
and, as you know, it has thousands and millions of cells,
and these cells have many connections.
So what might be actually happening when we form a memory?
Well, deep within the brain,
there’s a structure called the hippocampus.
It’s just inside here, in the medial temporal lobe,
on both sides of the brain –
at least in most people –
and this area of the brain is critical
for actually forming the connections that enable you to make a lasting memory.
And the reason it’s critical
is because information comes into your visual system at the back,
or your auditory system, the smell,
and passes from these sensory systems
through various perceptual systems
and down to this single area of the brain,
which is able to somehow connect all this information together,
and it, through an automatic process, makes those connections.
Now, the person who first suggested
that changing the connections in the brain was critical for memory
was Santiago Ramón y Cajal.
And he did so in his book, first published in Spanish,
later in French in 1910,
and in a very famous lecture given at the Royal Society in 1894.
And he spoke about mental gymnastics
changing the strength of connections between neurons in the brain.
And what he did through painstaking work
was to draw the cells that he found in lots of different areas of the brain,
in lots of different animals.
And this is one of his most famous drawings,
which is here in the Cajal Institute in Madrid.
This is actually his drawing of the hippocampus,
which I’ve just been talking about.
It’s a beautiful structure and it’s three-dimensional,
up here and so as you’ve seen,
but its intrinsic structure has this beautiful connectivity
which somehow enables information from these various different areas
to come together,
and we are in the process of trying to understand
exactly what mechanism is involved in making that happen.
And one discovery was that, indeed, the connections can be changed in strength
as shown in physiological experiments.
We’re beginning to understand some of the pharmacology and biochemistry,
and I, over about 10-15 years with my team in Edinburgh,
tried to do a number of animal experiments
to rigorously test the idea
that changing the strength of connections really was involved in memory.
And the gist of it is
that a particular transmitter in the brain called Glutamate
binds to a particular receptor,
just like a key going into a lock.
And when that happens, it triggers biochemical changes
which increase the strength of these connections
and in that way make connections
between different types of sensory information.
Now, you may be wondering
if this automatic processing is going on all the time.
Isn’t there a risk that the system would become completely saturated?
You’re making memories every second, every minute, every hour,
through the day …
Couldn’t the system then get completely filled up?
Well, that is what happens, isn’t it?
You know, at the end of the day after a busy day,
your brain is completely full, you can’t take it anymore, right?
You’ve got too much information in there.
Well, this is where, in keeping with the theme of subtract,
forgetting comes to the rescue.
Because it turns out that this process
of synaptic potentiation
happens very suddenly when events happen,
but then the synapses, gradually, over time,
a few hours, and at most a day or two,
move back down to the lower level of strength
that they had at the beginning.
So, what does that buy for you?
I’m sure you’re all aware that evolution’s very clever
and it works out, somehow, how the best way to do things.
Well, what this buys for you is that you’re capturing all of this information,
and then you’ve got, as it were, some period of time for your brain to,
as it were, work out what’s worth keeping and what’s not worth keeping.
And let the boring, inconsequential stuff fade away.
So, if I were to ask any of you what you had for breakfast
exactly a month ago, on August the 2nd, 2017,
unless you have exactly the same thing for breakfast everyday,
I suspect most of you can’t remember –
unless you were on holiday and sitting in a cafe in Formentera,
and the next table had some famous film stars
or something like that, then maybe you could.
But this information fades away.
Now, evolution has a further trick up its sleeve,
and that is that during this period of time of forgetting,
other things may be happening which, as it were, shed light
on the information you’ve just been processing;
they may turn apparent inconsequential information
into something of some significance.
And this happens in situations of great novelty or surprise,
or particularly when rather terrifying things happen.
So, if I ask anybody in this room
what was happening to you on the 11th of March, 2004,
you would, of course, remember:
11-M.
That was the day of the tragic bombings
in the commuter trains between Alcalá and Atocha,
not so far from here.
And it was a terrible tragedy –
may well have affected one or two of the families
of the people here in the room.
But when we think back to that,
of course, there’s the devastating images in our mind
of the wrecked trains that you saw on the news and in the papers,
but I suspect for many of you,
you also remember many of the trivial events of that day.
Perhaps what you had for breakfast, who you were with, where you were,
who you were talking with, and so on.
Because it appears as though,
in situations where novelty or surprise happens,
particularly something that’s kind of terrifying,
there’s an upregulation of the arousal system
and then a kind of “print now,”
of capturing everything and arresting this forgetting process –
such that you keep everything.
Because, after all, if something very surprising happens,
then even the most innocuous things may really matter,
so you might as well keep everything.
Now, I became very interested in this phenomenon,
and decided it would be interesting to try to do some animal experiments on it
with a view to trying to understand the underlying biochemistry
of what actually might be going on.
So, we set up some experiments in which rats and mice
were taught tasks which they forgot within a day:
they’d learn something, then they’d forget it, over and over.
So, that provided us a kind of platform
in which we could then, every so often, investigate the impact of novelty.
And we devised a way
of giving a somewhat innocuous novel experience to an animal
by putting him into a square box
which had a floor with either carpet or tea or rice or something like that,
and of course the animals are sensitive to these surfaces
and found it a novel experience.
And when we did that,
then it turned out the animals remembered for very much longer.
The question we wanted to go on to ask was exactly what cells in the brain
and what biochemical mechanism may be repsonsible.
So we turned to an amazing new technique called optogenetics.
In optogenetics we combine the power of light
with the power of genetics in a single tool
that was developed at Stanford University in Palo Alto, in California,
and the idea is as follows:
That you, in a surgical operation,
implant a virus into a particular area of the brain
that you think might be responsible for this novelty effect.
And what you implant is something called channelrhodopsin inside the virus,
and channelrhodopsin has the clever property
that when it’s expressed inside the cells because of the viral administration,
then if you direct blue light through a little light guide
as you can see in the picture,
down precisely onto those cells in the brain,
they will activate.
And we discovered that there’s a group of cells
called the locus coeruleus,
which is heavily involved in arousal and activation,
which also project to the hippocampus,
and which appear to provide this kind of “print now” signal.
And so, instead of giving the animals novelty,
we would teach them something,
they were on the process of forgetting it all,
and then we’d fire up the blue light –
and lo and behold, they remembered it for very much longer.
So that was an experiment showing both sufficiency,
that novelty produced the activity of the cells,
and necessity, namely that the activity of those cells
was essential for the process that we were observing.
So my message to you today has been
that when we make memories, there’s this instantaneous mechanism
of synaptic potentiation
that makes synapses stronger because it’s connecting
different bits of information together.
But the system doesn’t become saturated
because there’s this forgetting process,
this decline of synaptic efficacy
over a period of hours or days.
And if that didn’t happen, we’d be in serious trouble.
And so what’s critical, also, to the hippocampus doing its job
is indeed forgetting
because it clears, as it were, the desktop of your mind
so that you’re ready the next day to take in new information.
So forgetting is very important.
To finish, I’d like to speak to all of the partners in this room.
The husbands and wifes, boyfriends and girlfriends.
You’ve perhaps been in situations where your partner has complained
that you’ve forgotten to do something.
(Laughter)
You’ve forgotten to take out the rubbish –
“La basura.”
You’ve forgotten to give the cat his milk –
“El gato, el leche.”
(Laughter)
You’ve forgotten to pick up the kids from football!
(Laughter)
Well, just remember
that a memory scientist told you what to say.
(Spanish) It’s very easy.
(Laughter)
(Spanish) Darling,
(Laughter)
(Spanish) I’m sorry I forgot, but it’s normal!
(Laughter)
(Spanish) Thank you.
(Applause)
”
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