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Mind Over Molecules: The Biology of Memory | World Science Festival — Transcript

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0:01[Music]
0:10[Music]
0:17our memories Define
0:20us they shape who we
0:24are they guide how we
0:28Act
0:30they connect us to the
0:35world but how well do we understand the
0:38Pathways in the brain by which memories
0:40are imprinted Consolidated and later
0:44retrieved how does emotion affect the
0:47things we remember and will science ever
0:49gain the capacity to Tinker with our
0:52memories implanting new ones and erasing
0:54things we'd rather
0:56forget and how does the unconscious mind
0:59interface with conscious
1:02memories these are but a few of the deep
1:05questions that scientists investigating
1:07the mind and memory are vigorously
1:10exploring award-winning Professor
1:12Christine alberini is one of the fields
1:15leading
1:17lights Dr alberini is a chaired
1:20professor of neuroscience at New York
1:22University where her work focuses on the
1:25molecular and cellular mechanisms
1:27underlying the formation storage and
1:29retrieval of long-term
1:31memories thank you so much for joining
1:34us you know in in common language when
1:38we talk about memory in informal terms
1:41you often think of it as this like
1:43singular monolithic quality
1:46characteristic of the brain that it can
1:49make memories but of course there seem
1:52to be many different kinds of memories
1:54from the point of view of experience
1:57right we have things that we just
1:59automat ically remember tying our shoes
2:02how a chew there are abstract things
2:05that we just know about like the meaning
2:08of time and a year or a cat or a dog
2:12there are experiential memories episonic
2:15memories of things that we've
2:17experienced in our day-to-day lives is
2:19there a taxonomy of memories that helps
2:22us organize the different types of
2:25memories
2:26absolutely uh there are ways to
2:30uh distinguish memories in and classify
2:33them for example according to the
2:35duration we have shorter memories and
2:38longterm memories and we all experience
2:40that shortterm memories they last for a
2:42few seconds or minutes longterm memories
2:45they last for days weeks months even a
2:49lifetime and we all remember events
2:53single events that happen to us for
2:57sometimes the rest of our life those
3:00obviously are special specially longterm
3:04memories and we will discuss about that
3:08uh another ways to classify them is
3:10according to the system the so-called
3:12memory system that processes the
3:15information meaning the learning the uh
3:19uh formation of the longterm Memories
3:21the storage the retrieval and so on and
3:25there are different memory systems uh
3:28two main ones are classified as
3:32implicit and explicit memory systems and
3:36in the explicit memory systems we have
3:38the memories that we recall
3:42consciously so if we are here and we
3:44memorize today and tomorrow we can talk
3:47about it with our friends or a week from
3:50now or a month from now those are
3:52conscious memories meaning they require
3:56Consciousness when we recollect them
3:59those are part of the explicit memory
4:02system uh in those we have
4:05autobiographical Memories We have uh
4:08spatial Memories We have episodic
4:11memories and part of those are also the
4:15semantic memories conceptual memories
4:18memories of some abstract concept so
4:22when I say a dog you all know what I
4:25mean but you are not thinking of one
4:27specific dog perhaps you think about one
4:31specific dog in an episodic type of
4:34memory a memory of an episode of your
4:37life with those details that specific
4:40dog in that context and so on but the
4:43concept of dog which is a abstract
4:47concept comes from learning and is
4:50memorized so those are also different
4:53type of memories also belonging to the
4:55explicit memory system then we have the
4:58implicit types and those in those we
5:01have many I'm not going to go into all
5:03the classifications but the general uh
5:07definition of implicit memories is those
5:09memories that when they are recalled
5:11they are recalled in an automatic way
5:15without Consciousness so we just for
5:18example the memories of how to do things
5:20how to tie our shoes how to ride the
5:23bike and so on and so forth so those
5:26memories are recalled in an un conscious
5:29way they're automatic we do those action
5:33automatically so that is the one of the
5:36major distinction between the different
5:39types of memories according to memory
5:41systems memory system means the system
5:44that in our
5:46brain process those type of information
5:49in terms of
5:51learning uh storing the information
5:53recalling the information rearranging
5:56the information in the present in order
5:59to change update The Memories We
6:01constantly update our memories so we're
6:04going to dig a little deeper in just a
6:06little while but before we do that just
6:07from a more overview sense I think
6:10everybody can understand the distinct
6:13kinds of memories that you just alluded
6:16to how well do we understand the way the
6:21brain processes the information that
6:24must be distinct presumably for these
6:27distinct types of memories do we each
6:30pathway that's a very good question we
6:32actually don't
6:34know uh the mechanisms and now I'm
6:38talking about referring more to the
6:41biological mechanisms so cell biology
6:44molecular biological mechanism genetic
6:46mechanisms involved in these
6:50memories uh the stud is at this level
6:54are quite young it's they started in the
6:59late late 80s early 90s last century so
7:03we're talking about 30 40 50 years if we
7:07consider really the very very beginning
7:10it's a very young field and during the
7:14first 10 years it was very difficult to
7:16get to
7:18identify what are the molecular
7:21mechanisms of longterm memories and so
7:24what the field has done is to use very
7:26simple systems invertebrate system sys
7:30like a seil called aesia C fornica or
7:34the fruit fly dropil melanogaster those
7:37are two systems that have been very
7:39useful to inform Us in terms of the
7:42genetics and the molecular mechanism of
7:44memory from the very early days and from
7:48that understanding then the field went
7:51on to into studying molecular and
7:54biological mechanism in more complex
7:57systems because nothing was known so it
7:59was very important to start from very
8:01simple systems where the number of
8:04neurons is very
8:05limited where the tools to ask questions
8:11are uh easier because the system is is
8:15very simple and would you say that
8:18there's strong
8:19evidence that the mechanisms the
8:22pathways by which memories are formed
8:25are similar across all life on earth
8:28right so I was get into that sorry for
8:30the long introduction but yeah so from
8:33that uh then the field went into asking
8:36whether those mechanism found in those
8:38systems are also used by more complex
8:41systems meaning different memory systems
8:45in more complex
8:46organisms and it it has not been very
8:50easy to get the comprehensive
8:52understanding of the mechanisms
8:54characterizing the different systems so
8:57we just started from what we knew from
8:58the simple system and just ask the
9:00question are those used also in the more
9:03complex systems which means we are
9:06looking we are getting what we ask we
9:09are asking whether the same mechanism
9:12are used so we're getting that type of
9:14answer yes they are but so many others
9:18which are
9:20distinctive which are not completely
9:22known are certainly to be discovered I
9:25mean is it a challenge that the fruit
9:26fly can't respond to questioning
9:30they
9:32can no definitely you know there are
9:35simple memories that are tested and uh
9:38and you we we have to consider the
9:41question in the evolution right yeah and
9:44so one type of memory that is
9:46evolutionarily conserved is is or are
9:50memories that are important for
9:54survival one of the major question of
9:57memory is to make sure we remember
10:00something that is dangerous so that we
10:03don't do it again and we put ourself in
10:07danger all the time so if we memorize
10:09that and those systems are very very
10:13strong uh then we protect ourself from
10:17danger or from you know disappearing for
10:20for decreasing the decreasing the
10:23possibility that the species Will
10:25Survive so it's survival simple survival
10:28that is present in drosophila in the
10:31fruit fly in apesia in all the simple
10:34systems in the sea Elegance in the worm
10:37and uh as as much as in humans and do
10:42you have a a clear understanding of the
10:45survival value of each of the kinds of
10:48memories that you're referring to
10:49because clearly if you remember a
10:52dangerous episode in your own past
10:55you're less likely to repeat it which is
10:58something that will enhance your
10:59survival pass your genes for doing that
11:02onto the Next Generation and so forth
11:05but what about memory that is more for
11:09personal identity as opposed to directly
11:11for survival is it a byproduct of The
11:15evolutionary process or is it just
11:17something that complex neurological
11:21systems are able to do it's just one of
11:23those things that happens the the way I
11:25see it is everything is coming from
11:29an
11:30important uh an important requirement
11:33From
11:34Evolution um so memories are clearly
11:38essential functions for survival and for
11:41everything we do every day so one is to
11:44protect ourself from danger but the
11:46other one is to find the best resources
11:49for the most adaptive behavior that
11:51every day we have to
11:53do uh in that there is
11:57also
11:59what memory does to each individual
12:03which is creating a system that is very
12:08individualized and it is very
12:10individualized because we learn every
12:12day in different ways in different
12:15context so why this individualization is
12:18important in evolution is that if we are
12:22transported in in another place in a
12:25different context where we have to adapt
12:28to that
12:29context and we're going to do that
12:31through learning we have to be able to
12:33do so so in other words we are who we
12:38are because of our memories memories in
12:42in the large sense implicit and imp
12:44explicit types memories that change
12:47every day that uh change according to
12:51the new experience so we have a lot of
12:55um um storage of information recall of
13:00information and then new learning in the
13:03context of what we have learned and this
13:06happens throughout life just think for a
13:09moment what will be your life without
13:13memories it cannot exist simply it
13:17cannot exist so it's an essential
13:19function but it works in a way that
13:22every day we are learning something new
13:26and we place that new information into
13:28the history of our system and that is
13:31the memory meaning the storage of
13:34information and and of course there are
13:36pernicious diseases which Rob us of
13:39memories do you think of those at all in
13:42an evolutionary sense because after all
13:45if memory is
13:47evolutionarily part of our strategy for
13:50survival after we pass the age of
13:53reproduction the disintegration of
13:56memory should have no impact and why
13:58would the body wake waste energy on
13:59preserving these memories when it
14:01doesn't need to preserve you for
14:02survival any longer is is is that a
14:04useful way of thinking yeah that's and I
14:07don't have the answer for that right
14:09because if we think about Evolution and
14:11survival after we reproduce what's the
14:14use of it but I I would think uh that
14:18the use is to help the group the species
14:24to be in a better
14:26adaptive uh context
14:29so this um and this is you know there is
14:32no realove for that but logically we can
14:37think that in groups we
14:40create conditions that are more adaptive
14:43or can resolve certain problems that we
14:47Face uh in a different way than the just
14:50the individual would do sure so that
14:53that would be my answer yeah um and it's
14:56important to think about memories
14:58throughout life at different ages
15:01because they're different so memories of
15:04a newborn learning a memories in a
15:07newborn clearly are very different than
15:11learning a memory when we grow up and we
15:16are at a different age but still very
15:18young or adolesents or young adults or
15:21middle age or aged and each of these
15:26stages clearly comes with different
15:29biology so what we are very interested
15:32in studying is the biology that changes
15:35throughout different ages and how this
15:38biology is used by the memory system to
15:43create new memories to recall old
15:46memories to uh create new learning in
15:50the history and adoptive so digging down
15:54on that if we can just maybe do an
15:57example almost an ex exercise so
15:59everybody in this room is
16:01experiencing the conversation that we're
16:03having hopefully it's forming Memories
16:05We hopefully long-term memories so it
16:07doesn't just go out of mind an hour from
16:09now if that is happening inside the
16:12brain of either a person watching this
16:14live or digitally can you take us
16:17through in Broad brush or microscopic
16:21detail whatever you choose what's
16:23actually happening inside the head of
16:25someone who is forming a memory of our
16:29conversation right so memories of an
16:31episode like this will become
16:34longterm if they are important to you if
16:37they're important to you it means that
16:39there is an
16:40arouser it means that some hormones and
16:44neurotransmitters that are important for
16:46processing attention arousal excitement
16:50are released in the brain so those
16:52systems talk to the memory systems so
16:57other networks of cells not only
17:00neurons you know neural science is very
17:04centered on neurons which is rightly so
17:08however there are many other types of
17:09cells in the brain and they all
17:11cooperate for all these processes that
17:14happens so what happens is that these
17:18hormones uh and and systems that
17:22modulate the memory systems themselves
17:24so the network of cells that store
17:29uh and storage actually I'm going to go
17:31back to this that store the information
17:33long term they create biological changes
17:37over time it takes time to form memory
17:41so this memory that you form today no
17:44matter how longterm it's going to be uh
17:47but let's say it will be a longterm
17:49memory uh is not now stored in a strong
17:54way right now there is a representation
17:57of what's going on here here which is
18:00actually fairly detailed because you
18:03know what I'm saying what Brian is
18:06asking who is around you uh you see the
18:10details of the room and so on and so
18:12forth but this is not the longterm
18:15memory that will last a number of
18:17changes happen in the brain based on
18:20biological activation of Pathways for
18:23example there is gene
18:25expression transcription and translation
18:28those are the two major mechanism in
18:30biology transcription of genes
18:33translation of mrnas are essential for
18:36longterm memories so the way we
18:38distinguish longterm memories from
18:40shortterm memories is by looking at
18:43whether they require transcription and
18:45translation this is a Hallmark of
18:47longterm memories so transcription
18:49translation happens in our circuitry of
18:53memory circuitry of episodic type of
18:55memories one major region involv is the
18:58HP
18:58hampus but the hippocampus cross talk to
19:01many others cortical regions and other
19:04regions they get the input or the
19:07regulation the modulation from amigdala
19:10for example uh from other areas of the
19:13brain that tells that this is an
19:15important event to memorize and all
19:18those molecular changes in all those
19:20brain regions they change over time the
19:23first 24 hours are very important but
19:26they continue to happen for days and in
19:31some cases also weeks weeks that meaning
19:37that the hippocampus and cortical
19:38regions for example
19:40reverberate keeps talking to each other
19:43and all that biology that occurs over
19:46all this time is essential for forming
19:48longterm memories if there is an
19:50interruption of those mechanisms
19:52longterm memories are not going to be
19:54formed the the earlier the interruption
19:57is the disrupt ition the more the
20:00longterm memory will be absent will be
20:04disrupted uh so there the uh in other
20:07words there is a a Cascade of molecular
20:10events that happens in the brain that
20:13over time create a stable representation
20:17and this stable representation changes
20:19as I mentioned over time and over weeks
20:22it shifts from certain regions to others
20:27until it Bec this memory is called
20:30Consolidated so in other words memories
20:32are fragile when they're form over time
20:35they consolidate once consolidation is
20:39completed the memory is stable and if we
20:43try to interfere with the molecular
20:46mechanism there is no effect anymore the
20:48memories now you mentioned transcription
20:50and translation as a vital part of going
20:52from short-term memory to longterm
20:54memory and so that's the production of
20:56certain proteins presum ably do we
21:00understand how the production of those
21:03proteins are essential to the memory
21:06moving to the longterm phase do do we
21:09understand that well at the molecular
21:11level well is is too much it's pushing
21:13it okay but certainly this was one of
21:15the questions that started as I
21:18mentioned in the late 80s to understand
21:20what molecules what genes are expressed
21:23to form longterm memories what proteins
21:25are made where do they go what do do
21:28exactly in the brain uh for how long is
21:31this are these mechanisms involved and
21:33so on and so forth and and of course we
21:35have addressed some of the questions but
21:36not all of them so there is this Cascade
21:40of gene expression so a number of genes
21:43are transcribed and then translated into
21:46proteins there are also many other
21:49levels of Regulation chromatin changes
21:51of course when there is gene expression
21:53there is also chromatin
21:54changes uh and uh also the uh
21:59transcription of rnas that are not
22:02translated into proteins but regulate a
22:05number of steps so there are there is
22:07there are so many steps at at the
22:09biological level that converge into a
22:12Cascade of
22:14mechanisms my lab as many others have
22:17focused on the which transcription
22:21factors and and Gene trans genes are
22:24transcribed in the brain in these brain
22:26regions which are required for long-term
22:29memories and many others have looked at
22:31the translation of this mRNA so we and
22:35others of course have identified a
22:37number of mechanisms of Pathways that
22:41are essential for longterm memory
22:44information longterm memory storage as
22:47well as uh whether they are re-involved
22:50when we recall memories that's another
22:54interesting I wanted to ask you about
22:55that because from from an experience IAL
22:58standpoint just anecdotally when I've
23:02wanted to remember something long term
23:04even when I was a student what I would
23:07do is 15 minutes before the next lecture
23:10I would review the previous lecture and
23:13I found just by reimagining and
23:16rethinking about the material from the
23:18previous it just stuck in a way that was
23:21more potent for me than cramming it in
23:24at the end and when I have to you know
23:27give some kind of presentation I want to
23:29remember this or that I find just a
23:31little 10-minute reminder every single
23:34day is what makes it go from short to
23:36long is is that consistent with your
23:41understanding of how long-term memory is
23:42formed it is it is we have studied what
23:46recalling memory uh
23:49does when we recall memories of course
23:52is you know uh intuitively we recall
23:55memories because we need we need to do
23:59something we need to make a
24:02decision uh but what happens in the
24:04memory system and why is this recall
24:09important yes and it is important as we
24:13found to strengthen memories but clearly
24:16the recall is not as the learning
24:20event so it's a
24:22different uh processing of the memory is
24:26not exactly
24:28strengthening uh completely the memory
24:31that we originally had in the learning
24:34event but we recall and perhaps is a
24:36partial recall and that is strengthening
24:41the memory this is is is also what we
24:43found but when uh this was studied in
24:47terms of molecular mechanism it became
24:49very interesting because so as I
24:51mentioned longterm memories required
24:53gene expression and it was believed that
24:56once memories consolidated
24:58is no longer uh sensitive to disruption
25:01or
25:03changes uh of course it can be change
25:06with new learning uh but a number of
25:08studies show that when memories are
25:11recalled they become fragile again for a
25:15limited temporal
25:17window uh similar to what happens with
25:19no learning and during the temporal
25:22window again they require transcription
25:24translation to stabilize in other words
25:26there is a reconsolidation ation
25:28happening with the retrieval the recall
25:30of the memory so a memory recall can be
25:33dangerous then in a way this doesn't
25:35happen with all the memories and all the
25:38time but it happens and so it can be
25:40dangerous right so why should it be if
25:43it is
25:44dangerous why actually does it happen
25:47nature doesn't work that
25:49way it happens because with that
25:53fragility we can actually strengthen the
25:55memory so it is a way it's like a
25:58tradeoff memory it's a tradeoff you you
26:00go into a danger zone of modifying or
26:03losing the memory but the upside is by
26:06undergoing this process you strengthen
26:08it if it survives in most cases you will
26:10not lose it you have to interfere yeah
26:13in order to lose it in other words no
26:16learning could do that could interfere
26:19and this is why memories are not precise
26:21because constantly we recall memories we
26:24have some new learning coming in uh and
26:27Al decays of memories forgetting is
26:30another process of memory of course very
26:33important we need to
26:35forget uh so all the combination of
26:38these
26:39creates the the way memories work but
26:42they cannot be precise because we
26:44constantly change them so another way
26:48through which these recall dependent
26:50changes work uh is to incorporate new
26:55information into the old old
26:57representation so we recall and now we
27:00associate something new to that uh so
27:05this uh uh mechanism or process is
27:08called reconsolidation it has been
27:10studied quite a bit it generated a lot
27:12of interest particularly if we want to
27:15think about uh for example diseases like
27:18post-traumatic stress disorder or
27:21addiction yes where the memories are
27:23very
27:24strong memories of trauma and there're
27:27also very distinct right they're
27:30distinct from normal
27:32memories uh postraumatic stor addiction
27:36the memories of how the uh substance
27:40feels is very much connected to
27:44context people who are addicted relapse
27:47when they go back to the old context
27:50because the memories of it make them
27:53relapse so there was a lot of interest
27:56when this reconsolidation and temporal
27:58window of intervention let's call it uh
28:02emerged because the field thought well
28:05it could be an interesting approach to
28:08actually decrease the strength of those
28:11memories and help the process of
28:14therapeutic so I don't remember the
28:16mechanism in Eternal Sunshine of the
28:18Spotless Mind but was that the basic
28:19idea that they were restimulating the
28:22memory and getting in there and somehow
28:24ering exactly like that it is exactly
28:27like we see this in in in the lab so if
28:30we take an animal we use we work with
28:32rats and mice with rodents we take an
28:35animal they learn something and then we
28:38make them recall that memory and during
28:41the temporal window of reconsolidation
28:44we
28:45intervene with it can be in different
28:48ways to interfere with the
28:51reconsolidation process uh they they
28:54forget not that they forget they lose
28:56the memory because they cannot
28:59reconsolidate it so the they can't run
29:02through the maze anymore or something
29:03like that the memory decreases wow now
29:05you you you also made reference to
29:07emotion being an important part of
29:10long-term memory formation so and then I
29:14don't mean this to sound factious but
29:16I'm actually wondering so you know if
29:18I'm studying general relativity I'm at
29:20my desk and I'm usually pretty calm as
29:24I'm going through the ideas in the
29:26equation say but if I was to somehow be
29:29much more excited and and emotionally
29:32disturbed or or in some friends you said
29:36is there a better chance that I will
29:37remember the material in a longterm way
29:40sure for sure but you know we know we
29:42know that right even
29:47caffeine right I'm I just I don't want
29:50to
29:51mention other stuff no feel free we're
29:54yeah you know we already have this EX
29:57examples throughout you know many years
30:00we have we know that see I would have
30:02always thought caffeine or artificial
30:04stimulants were viewed and I'm learning
30:07in this conversation they to me were
30:10just focusing your attention more fully
30:13because you're more awake but not
30:14because you're emotionally aroused no
30:18but attention is one way to increase the
30:23uh storage of long-term Memories the
30:26other is arousal as you say so is is a
30:31similar is is a similar consequence yeah
30:34this hormones can increase do increase
30:38the biological changes as I was
30:41mentioning happening in the memory
30:42system which lead to morphological
30:45changes in other words there is a
30:48physical change in the brain in those
30:50circuitry that store
30:53memories as my advisor used to say I
30:57train at Colombia with arand sure uh
31:00after an event if you form a longterm
31:03memory you have another Wrinkle in your
31:06brain and um so just thinking about the
31:10the wrinkles for a moment
31:13um if one is trying to enhance longterm
31:20memory which I think many of us want to
31:22do I mean it's very frustrating you
31:23learn something and then a week later
31:26you you just can't grab a hold of it
31:29what are the effects of other things
31:31like like sleep or or dreaming does that
31:35have an impact on our capacity to retain
31:38information some people say study it
31:39just before you go to sleep in order
31:41that the brain can consolidate is is
31:43that real is there evidence for that so
31:45there are evidence the the most I I
31:50think interesting evidence for students
31:52is that do not Crown because in order to
31:56form a longterm memory the brain needs
31:59time as I said this is a a process of
32:02biology that requires time memory
32:05consolidation if you go right after your
32:08learning with another learning
32:12event another consolidation process
32:14going to start then the brain is
32:16confused you're not going to remember
32:19well which is the first learning piece
32:22or the second learning and these
32:24experiments have been done more than 100
32:26years ago shown right so that's called
32:29retroactive interference if you go with
32:32a second learning event to uh close to
32:35the first one the two events are not
32:38going to be remembered well in a
32:40separate way so do not give
32:43time now sleep is very important that's
32:47very well known that if sleep or
32:49circadian
32:50rhythmicity is altered consolidation is
32:54going to be impacted because those those
32:57mechanism of circity and sleep they work
33:00together with the consolidation process
33:03the biology that I mention all that
33:05Cascade
33:06includes uh a number of modification
33:09that happens through the Circadian
33:11rhythm as well as what happens in sleep
33:14where the representation is
33:17replayed so this replay is important for
33:20the consolidation so if you we disrup
33:22not the biology is part of
33:24these processes if we disrupt any of
33:28these processes and we can go with a
33:30biological mechanism or uh or new
33:33learning or behavioral
33:35approaches uh then we disrupt the
33:39ability of the brain to form longterm
33:42memories in the best way now can we
33:45enhance memories we can we have found
33:48molecular mechanisms that can do that
33:51very nicely one example we have in the
33:54lab is it's a small protein it's called
33:57insulin like growth F Factor 2 igf2
34:00insulin like growth factor 2 and igf2
34:04belongs to a um family together with
34:09another igf igf1 and
34:11Insulin uh but these three proteins they
34:15do very they have very different
34:17functions and igf2 we discover to be
34:20regulated in brain regions important for
34:23longterm memory like the hippocampus
34:25with
34:25learning and to be required for longterm
34:29memory formation in other words if this
34:31production of igf2 that occurs in the
34:33hippocampus with learning is
34:35blocked longterm memories do not form so
34:38it's required can you do it artificially
34:41can you add and then we added so you can
34:45deplete the system or you can add right
34:48so then when we added
34:50igf2 without interfering with anything
34:53else just having the learning event the
34:55memories will spectac ularly more uh
34:59stronger and more longer lasting this is
35:01in rats this is in rats and mice uh and
35:06this small peptides protein can actually
35:09be injected even systemically like
35:11insulin can be injected subcutaneously
35:14we can do that with igf2 and we have
35:16these animals that have a super memory
35:19very strong and long lasting significant
35:23effect so then of course we became
35:26interest Ed in studying memory
35:29enhancement in the normal animals but
35:31also whether this could be a potential
35:34Therapeutics for memory disorders we
35:37have an incredible need for novel The
35:41Therapeutics that can work for memory
35:43disorders and you've not tried on people
35:45and we have not tried on people but I
35:47started a company because the data that
35:50we have seen in the lab are you taking
35:51investors in this I do
35:55okay
35:57so this igf2
36:00reverses not only cognitive impairment
36:03so we in the lab we have tested aged
36:06animals and the cognitive impairments
36:09related to aging is reversed we tested
36:12models of neurodevelopmental disorders
36:15like autism Angelman syndrome is a
36:18genetic neurodevelopmental
36:20disorder and these are characterized by
36:22cognitive impairments so we reverse the
36:24cognitive impairments but also the other
36:27problems that they have and that was
36:30very exciting but also surprising I have
36:33to say for example in Angelman syndrome
36:36they have Motor problems in addition to
36:38cognitive problems they have repetitive
36:41behaviors like
36:42autism uh they often have seizures and
36:47with igf2 we reverse all of these so it
36:52sounds like a miracle but it must be a
36:53downside right exactly so we started ing
36:57what are the downsides do we see for
36:59example the memory that that are
37:01potentiated in the normal animals are
37:04they more rigid no they're not do we see
37:07any obvious um uh effect side effect we
37:12have not seen but of course these have
37:14to be tested in a different ways if we
37:16want to go to to uh to people of course
37:21uh so so far it's really very exciting
37:25what we see with this igf2 not only as a
37:28cognitive enhancer in normal normal
37:32individuals or normal animals but also
37:35as a potential Therapeutics for a number
37:37of diseases so what do they have in
37:41common uh Aging for example aging
37:44related cognitive impairment with
37:45neurodevelopmental
37:47disorders and other labs have studied
37:50igf2 in Alzheimer disease models in
37:54Huntington disease models and again all
37:56beneficial effect with igf2 what do they
37:59have in common they have in common that
38:01they accumulate proteins in the brain
38:05different type of proteins in different
38:07diseases but the common problem is
38:10protein accumulation in the brain so we
38:13were very surprised to see all these
38:15effects and of course went into studying
38:18the mechanism for why this may happen
38:21and it turned out that uh this
38:24igf2 works through a re ctor that
38:27regulates protein metabolism in other
38:30words the making and breaking of
38:32proteins and spits up protein
38:36degradation that is the elimination of
38:39proteins in the protein metabolism is
38:42that like eliminating plaque is that a
38:44different type of thing so that's what
38:45we we want to do now we want to look at
38:48WEA in the disease models we eliminate
38:52those specific proteins let's say
38:54Alzheimer disease models that we see
38:56plaque elimination and so on and so
38:58forth some studies already have shown
39:00that that's the case with igf2 in the
39:02mouse model yeah so it's very exciting
39:06it sounds it um I want to just change
39:08gears a little bit um one of the
39:12interesting realizations in the last few
39:15decades in the judicial system is how
39:17unreliable eyewitness memory and
39:20testimony can be H how do you view that
39:24from a a neuroscience memory
39:28perspective indeed we already touched
39:30upon that memories are not
39:34accurate uh I I think first of all from
39:38from my personal point of view we have
39:40to
39:41distinguish between what happened and
39:43the accuracy of memory right sure mean
39:46if somebody comes up with something that
39:48never happened is different than saying
39:52oh I have seen that person that day in
39:56that
39:56place this is where memories are not
39:59accurate because uh over time and uh and
40:04many rounds of similar memories for
40:08example if you return to this room 10
40:12times you will confuse who was at which
40:16time in this room and clearly this
40:20information is going to be less and less
40:23accurate as time passes so if I ask you
40:26tomorrow you have a more accurate memory
40:28but if I ask you a month from now or six
40:31months from now the memory is going to
40:32be less accurate considering that the
40:35repetition and uh the uh amount of
40:39information that we have to make sense
40:42with uh and what we do uh you can
40:47imagine how uh the information is uh
40:53confused in terms of who is in a certain
40:57place at a certain time and so this is
41:01where the the memories are not
41:03accurate we usually say you know if you
41:06talk to your family about a New Year's
41:10Eve together I don't know some festivity
41:13together and uh you start talking about
41:15who was there and what was said there is
41:18a complete disagreement about the
41:20members of the family especially if the
41:22the event was is dated right so over
41:27time uh the information gets confused uh
41:30and that's why the memories are not
41:32accurate so yes they can be and do you
41:35do you imagine that memories that are
41:38say inaccurate or degraded or people
41:41completely forget is the root
41:44information still somewhere in the brain
41:48I mean like a Freudian perspective would
41:50say it's always there it's always
41:52influencing you even from times that you
41:54don't even consciously remember is that
41:57a kind of Freudian myth or is there
42:00evidence that everything that's ever
42:03happened to you is somehow stored
42:05someplace and is affecting you in some
42:07manner yeah so I don't know I don't know
42:10how to answer that question the the
42:12fredian the fian essence though to me is
42:16different I actually at one point in my
42:18life uh trained as a psychoanalyst so I
42:21started as a biologist I'm a bio
42:23molecular biologist and I keep doing
42:26that but at one point I I studied as a
42:29psychoanalyst and
42:31that that Essence to me and this is what
42:35in influenced my studies in the lab
42:39actually comes from
42:41development so we're switching a little
42:44bit gears here it's not this everything
42:47is in our brain and everything we do is
42:49long is stored long term and that it can
42:53appear later I think actually the uncons
42:56ious but this is my interpretation I
42:58think the unconscious that frud is
43:00talking about that influences our life
43:04throughout uh comes from development the
43:08way we learn from day one even
43:13before the learning that happens through
43:16development is shaping the brain and the
43:19systems and I have started to study that
43:23that's why I became interested in
43:24studying the biology of learning and
43:26memory in infancy so we take infant rats
43:29and mice and look at the biology when
43:32they learn and what we found it was also
43:36very uh interesting and not predicted so
43:41we we went into the question without any
43:44mindset what we found is that in fact
43:48the brain in infancy is learning to
43:52learn for a certain temporal window
43:56and in that temporal window it's like a
43:58critical period it's a critical period
44:01that's exactly it uh in that critical
44:04period the system is developing and
44:07shaping according to the experience that
44:11the animal
44:13has That's the basis of individuality so
44:16it's not the specific details of the
44:19memory it's rather how the experience
44:21shaped the way the brain will
44:23subsequently function and it's open to
44:25that influence during this critical
44:27period right and in fact we see that the
44:30learning that they have in infancy
44:33creates what we call a schema because
44:36it's something that influences adult
44:39behavior and it influences in a way that
44:43the first the memory can be um
44:47reinstated I'm going to get back to that
44:49the infant memory and secondly uh it
44:54influences similar types of behavior and
44:57this happens only with the learning
45:00during that critical period so the
45:02reason why we we concluded that there is
45:06a critical period is because we tested
45:09it uh when we started to look at this
45:13biology uh it was believed that learning
45:17in
45:18infancy uh is
45:20forgotten and this is true so what do
45:23you remember of the first three years of
45:25your
45:28life but this is normal so this rapid
45:31forgetting that happens in this phase of
45:35infancy is believ to explain what's what
45:38is called infantile Amnesia the fact
45:40that as adults we don't remember the
45:42first few years of
45:45life the theories and what was known at
45:48that time when we started to investigate
45:51this they were suggesting that
45:53consolidation doesn't work because the
45:56memory system that uses the campus is
45:58not developed the campus is not involved
46:01it's
46:03offline uh so we started to give these
46:06infant rat mice learning events and then
46:09tested whether the memories could come
46:11back so that was the first question
46:13right if it's gone it's not going to
46:14come back we were able to see it coming
46:17back coming back it comes back so the
46:20the animal forgets because when you test
46:22them they they show no memory like
46:25humans
46:26there is a very rapid forgetting no
46:28memory but if you then later on test
46:31them with certain type of reminders you
46:33can get the memory back and you knew the
46:35specific reminder cuz you set up the
46:37situation witho yes but we tested a
46:40number of them before for us we wouldn't
46:42know how to do that but no we don't know
46:44and also it's unclear whether those
46:46memories that come back are
46:49conscious meaning they're conscious when
46:52they come
46:53back but do are they conscious about
46:56when they will learn we have no way to
46:59test it my view now is that those are
47:04implicit type of representation implicit
47:07type of memories not explicit I see that
47:10however later on they are recalled
47:14reactivated with some new learning or
47:17some reminder and then they create the
47:21expression of the explicit memory but
47:25the infuence what we do they influence
47:27what the animal does in adulthood for
47:30example we didn't test in the old age
47:32but up to adult for sure I can say that
47:36so the reason why we we concluded is a
47:39critical period is because we tested the
47:41biology in of that
47:45hippocampi and found that molecular
47:47mechanisms that we're identified by
47:50other studies in the sensory system as
47:53mechanism of critical period are used by
47:57our system the memory system to form
48:00these longterm memories that are not
48:02expressed but they can return and they
48:05influence adult Behavior that's that's
48:08kind of amazing um unfortunately we only
48:10have a couple minutes left I wanted to
48:12ask you a few more questions just to get
48:15your quick thoughts on these issues I
48:19think many of us have had the experience
48:21that music is an incredibly powerful way
48:25of bringing us back to an emotional
48:28state at some earlier time in our lives
48:31do we understand why music has that
48:34capacity uh here is out of my uh
48:39expertise but there are group studying
48:43music and how that influences brain
48:47activities and how that influence why
48:50you know we have this uh why we have
48:52this very strong recall with emotion is
48:56because music is a CU and that is
49:00processed by
49:02amigdala uh so there is a representation
49:05that is directly linked to the
49:09emotional uh systems basically but more
49:12than this I I cannot really say because
49:15it's not what I'm studying but yeah
49:18there are several studies going on with
49:19so so another question that may fall
49:21into that category if you don't mind so
49:24some of the greatest literature has
49:27explored human memory in in various
49:30aspects and approach is there is there a
49:32book out there that you consider to be
49:35one that really in an Artful way
49:38captures the the Wonders and Mysteries
49:41of memory is there anyone that comes to
49:43mind unfair questions so no no I would
49:47not even mention any because there are
49:51you know I would say there are several
49:53with different from different angles and
49:56different ways um yeah sure and a final
50:00thing you know the world is extremely
50:04excited about artificial intelligence
50:07now and you know it's a wideopen Arena
50:11but do you see those developments
50:13interfacing or intersecting with the
50:15kind of work that you do on the natural
50:19version of intelligence and memory uh
50:22they're
50:23already working together together uh so
50:28artificial intelligence is very much
50:31involved for example computational work
50:34is very much involved in understanding
50:36now all the types of mechanisms that are
50:40active in certain brain regions and how
50:44do they change and so on and so forth so
50:46data analysis because a lot of
50:49approaches now they're not looking at
50:51single mechanism they're looking at the
50:54comprehensive pattern
50:55so this is where computational comes in
50:59uh there are other ways to manipulate
51:01brain
51:03circuitry uh again is engineering
51:08certain uh
51:09mechanisms and creating artificial tools
51:14that can change the circuitry in the
51:16brain and therefore behaviors the these
51:19are just two examples but uh there is a
51:22lot also done in terms of theories uh
51:25that hopefully will inform experimenters
51:28how to test new questions about
51:31understanding the mechanism of memory
51:32and can you imagine just oblique to that
51:36but resonating with it will there be
51:39brain machine inter faces that enhance
51:43human memory is that a direction that
51:45you see bearing fruit I don't know um I
51:49mean in theory yes but I don't know how
51:52easy that will be because
51:56biologically uh considering the biology
51:59of it which is where I come from the
52:01brain constantly
52:03changes and this
52:05adaptability to whatever change comes in
52:09the environment is very difficult to
52:12recreate in a machine so we can create
52:16circuitry we can create we we can plug
52:18in a number of
52:20information uh it can be extremely
52:23sophisticated but how can we predict
52:26something we don't know so that's that's
52:29the bias I think yeah absolutely well
52:32it's been a fascinating conversation on
52:34memory across the various forms of life
52:37with that capacity thank you so much and
52:39please join me in thanking Christi
52:43Al thank you so
52:44[Applause]
52:46[Music]
52:54much
52:56[Music]
53:24a
53:26[Music]

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