The Storage of Memory: Functions of the Cerebral Cortex at the Cellular Level
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00:00
Meeting/Interview
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Computer animation
02:42
Computer animation
03:02
Meeting/Interview
03:36
Lecture/ConferenceMeeting/Interview
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Computer animation
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Meeting/Interview
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Computer animation
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Meeting/Interview
07:47
Computer animation
Transcript: English(auto-generated)
00:04
My research question is, what makes us intelligent, and how does conscious perception work? And to answer this, we've been looking at the cerebral cortex now for over two decades. And when you look at the cerebral cortex, which is perhaps the most complex object in the universe, you see what at first appears to be a jungle of neurons.
00:24
They look actually quite like trees, and the main neurons of this jungle have two specific ends. One end is like the leaves of a tree, and the other end is like the roots of a tree. The roots in this case receive information predominantly from the outside world,
00:41
whereas the leaves get information that's being generated within the brain, so internally generated information. The important observation that we've made is that the cellular properties of this cell bring together these two kinds of information in a spectacular fashion that allows us to make sense of the outside world in terms of our expectations.
01:02
And now we bring to this a new important topic, and that is memory. And memory is important because when you think about it, your memories dictate your knowledge about the world, and your knowledge about the world is basically your expectations about the world. And now perhaps you can see where this is going.
01:20
We want to know what drives the internal dance, or the dance between the internal information and the external information at the cellular level. Over the past two decades of research on this topic, we've been using methods to try to look at what's happening not only at the circuit level, but at the cellular level.
01:45
And that's required that we do quite sophisticated recordings, electrical recordings and optical recordings at the cellular level. And we've had to evolve and to transfer these techniques from brain slices in vitro
02:02
to recordings in a behaving animal. Over this time, we've made tremendous advances in understanding what's going on at the cellular level and how that contributes to the cognition in the animal. Now we introduce the topic of memory and how that relates to the system.
02:22
And this immediately comes with one of the biggest problems I think in neuroscience, which is that memory is a distributed phenomenon. That means that memories are fragmented all over the cortex. In order to investigate this, we started to use a new approach, and that was to train an animal to respond to the artificial stimulation of its own brain.
02:47
So we stimulate the cortex in a particular region, and we train the animal to lick for a reward when it feels this stimulation. And by doing this, we know where we stimulated and we know where to look for some of the mechanisms involved.
03:02
Now in addition to this, we've been using a new method called chemogenetics, or DREDs, which are a way of investigating with genetic manipulation pathway-specific information. Here, the pathway we're interested in is the influence of the hippocampus
03:20
and the medial temporal lobe on the neocortex. And we've been able to specifically inhibit one particular projection going exactly to the region that we've stimulated and investigate in general what mechanisms are occurring at this connection. So there was one overriding key finding in this research project,
03:44
and that relates to what kind of information the medial temporal lobe gives to the neocortex, and more particularly where this information goes to. And what we found was the medial temporal lobe projects to layer one of the neocortex, and that this is crucial for the animal's ability to learn.
04:04
This is a smoking gun for neuroscientists and for the kinds of questions that we're asking, because what it actually means is that the important signal that comes from the medial temporal lobe that is crucial for laying down memories goes to the top of the neurons that segregate internal and external information.
04:24
On the one hand, we now think we know where to look for memory consolidation in the neocortex. Now there were a number of subsidiary findings. First of all, we found that there was the emergence of different populations of neurons that emerged throughout the learning
04:41
that consisted of about 10% of the neurons that were upregulated or increased in their firing rates, and nearly 40% of neurons in the same area that decreased in firing. And then we came across another fact that we weren't expecting,
05:01
and that was that the mode of firing, that's to say the kinds of patterns that were being emitted by the neurons, also changed overlearning, and we think that now relates to memory. And in particular, by recording from single neurons and making them fire in particular patterns, we were able to show that the neurons that were being made to burst fire,
05:23
that is, fire at high frequencies, were able to be detected or change the behavior of the animal, whereas the same neuron that fired in a low-frequency mode was not detectable by the animal. And so we now think that memory involves the changing of the mode of firing of the neuron,
05:43
and this comes with the corollary that there is information in the patterns that are emitted by neurons, which has been a long-standing question in neuroscience, namely, what is the neural code of neurons? And at this point, we think that there is some temporal structure
06:01
to the output of a neuron that is recognized downstream throughout the brain. So the relevance of this research is both really exciting and gratifying because it's the culmination of over two decades of research now, and we're bringing together the question of memory
06:21
to the larger question of how the cortex operates. We're finding that the information that comes from the medial temporal lobe that determines whether or not you remember something arrives at that part of the neuron that codes for internal information. Now this makes perfect sense in the end
06:40
because this is the part of the neuron that is coding for your expectations. So essentially what it means is that your memory is the fine-tuning of your expectations, and also your knowledge is the set of things you expect about the world.
07:00
So now that we've got to this point, we have a new outlook for perhaps the next ten years, which is to now look at the mechanisms at the cellular level of what's occurring during memory storage. Because we now know where to look and what kinds of things to expect in which particular neurons, I expect now over the next ten years to be able to look in great detail
07:24
at the mechanisms that are occurring, and we expect them to be really relevant to memory storage. That will put us in a position, I hope, to be able to understand diseases and problems that occur with memory, and possibly on the other hand to understand ways that you could enhance or enrich memory
07:42
by up-regulating certain mechanisms. But that's yet to come.