Biology of Memory

Transcript

• 00:24Good day. My name is Leo Cooney.
• 00:26I'm an emeritus professor of geriatrics
• 00:29at Yale, and I'm here today to talk
• 00:31to you about the biology of memory.
• 00:33So scientists have learned a
• 00:35dramatic amount about the process of
• 00:38memory over the past few decades.
• 00:40And it's very important because if we're
• 00:42going to, if we're going to develop
• 00:44treatments to prevent and treat memory loss,
• 00:46we need to know a lot about how the brain
• 00:50lays down and maintains stores memories.
• 00:54So what is memory? How does it work?
• 00:56How does it change with aging?
• 00:59So memory is the capacity of an
• 01:01Organism to acquire, store and recover
• 01:04information based on experience.
• 01:07So there are two types of memory.
• 01:08There's declarative memory,
• 01:09which is a memory for facts and events,
• 01:12for people, places and objects.
• 01:15This memory requires the
• 01:16medial temporal lobe,
• 01:17and in particular the structure
• 01:19called the hippocampus that
• 01:21we'll be talking a lot about.
• 01:22Procedural memory is knowing how to
• 01:24do things, for example, motor skills,
• 01:27and that involves a number of brain systems
• 01:30depending upon the specific type of learning.
• 01:34So what is memory,
• 01:36Where is it encoded,
• 01:38where is it stored?
• 01:39How do nerves acquire memory?
• 01:42How do nerves store memory?
• 01:44And how are these processes disturbed in
• 01:48neurologic conditions such as dementia?
• 01:51So where is information encoded
• 01:53and stored in the memory?
• 01:55So the brain is made-up of a number of lobes.
• 01:58We want to focus today on two of those lobes.
• 02:01The first one is the medial temporal lobe,
• 02:05where shortterm memories are laid down
• 02:07in a structure called the hippocampus,
• 02:10and the other is the frontal lobe,
• 02:12sometimes called the cortex of the brain.
• 02:14And that's where longterm memory are stored.
• 02:19So the anatomical components of the medial
• 02:21temporal lobe support declarative memory,
• 02:23and again, that's the hippocampus
• 02:25and the power hippocampal gyrus.
• 02:27The hippocampus and related structures
• 02:29are essential for the formation of memory
• 02:32and its reorganization and consolidation.
• 02:35After learning,
• 02:36medial temporal lobe structures have
• 02:38a temporary role in memory storage,
• 02:41so the hippocampus rapidly stores the
• 02:44day's events before the information
• 02:46is transferred to the cortex for
• 02:49reorganization and classification.
• 02:50The hippocampus is a temporary repository.
• 02:53Waking patterns of nerve activity are
• 02:56reinstated and replayed during sleep,
• 02:59so sleep is very important to
• 03:02the brain's activities.
• 03:03So good sleep pattern is very important
• 03:07for strong memories and a healthy brain.
• 03:10Memories are assumed to decay more rapidly
• 03:13in the hippocampus than in the cortex.
• 03:15So when we study Alzheimer's disease,
• 03:18the structure where the first
• 03:20changes of Alzheimer's disease
• 03:22are found is the hippocampus.
• 03:24And that's logical because the hippocampus
• 03:26is where short term memories are stored
• 03:28and the first symptom of Alzheimer's
• 03:30disease is loss of short term memory.
• 03:32So the hippocampus is an important
• 03:34structure as we talk about memory
• 03:36and the things that affect memory.
• 03:38The cortex,
• 03:39or frontal part of the brain,
• 03:41is an outer layer of nerve activity
• 03:43of the cerebrum of the brain.
• 03:45It's the largest site of nerve
• 03:47integration in the central nervous
• 03:49system has a key role in attention,
• 03:52perception, awareness, thought,
• 03:54memory, language and consciousness.
• 03:57But it's also important because it's
• 04:00the site of longterm memory storage.
• 04:03So the hippocampus rapidly stores the
• 04:05day's events before the information
• 04:07is transferred to the cortex for
• 04:10reorganization and reclassification.
• 04:12The hippocampus is a temporary repository.
• 04:14The cortex is important for long term memory.
• 04:18So how do nerve cells store memory?
• 04:22So there are three components
• 04:23of a nerve cell.
• 04:24There's a body, there's an Axon,
• 04:27and that's a branching structure that carries
• 04:30nerve impulses away from the cell body.
• 04:33A dendrite is another branching structure,
• 04:35but that's the receiving part of the
• 04:39neuron that brings messages to the cell.
• 04:42It receives its input from axons
• 04:44at a structure called the synapse.
• 04:47The synapse is very important.
• 04:49That's the site of chemical and electrical
• 04:52communication between nerve cells at
• 04:55the junction of axons and dendrites.
• 04:57So here is an Axon branching
• 05:00structure leaving a nerve cell,
• 05:03taking impulses away from the nerve cell.
• 05:05Here was a dendrite,
• 05:07another branching structure taking
• 05:09impulses back to the nerve cell.
• 05:11And here is the synapse,
• 05:13Very, very important.
• 05:14So at the end of the Axon there are vesicles,
• 05:18and those vesicles contain chemicals,
• 05:21and those chemicals in the way in
• 05:23which nerve cells talk to each other.
• 05:25So we call those chemicals neurotransmitters.
• 05:28They're released by the Axon.
• 05:30They're received by what's called
• 05:32receptors on the dendrite.
• 05:34And that's the way messages are
• 05:37passed from nerve cell to nerve cell.
• 05:39But it's also this synapse is the
• 05:42place where memory is stored.
• 05:45So there's a pivotal role of the synapse
• 05:47in the neurochemistry of memory.
• 05:49It stores memory by changing the
• 05:52strength of that synaptic connection.
• 05:54We call that synaptic plasticity.
• 05:56We'll talk more about that later.
• 05:58Long Term Potentiation is a process.
• 06:01It's the process by which the
• 06:03synapse is strengthened.
• 06:05It increases the transmission
• 06:07between nerve cells.
• 06:09So synapses are the essential unit of memory.
• 06:13They're the site of electrical and
• 06:15chemical communication between nerve cells.
• 06:17And because the strength of these
• 06:20synaptic connections are modifiable,
• 06:22they're considered plastic.
• 06:23If you go to the dictionary,
• 06:24look up the word plastic,
• 06:25you realize that it means
• 06:27capable of being molded.
• 06:29So these synapses are capable
• 06:31of being changed or molded,
• 06:33and that's what impacts memory.
• 06:35So changes in synaptic strength
• 06:37are brought about by the release
• 06:39of these chemicals from the Axon,
• 06:41the neurotransmitters.
• 06:42Some changes in synaptic
• 06:44strength last only seconds,
• 06:46others persist over the
• 06:48lifetime of the Organism,
• 06:50And thousands of experiments over
• 06:52decades have shown over and over
• 06:56again that synaptic plasticity at
• 06:59appropriate synapses is necessary
• 07:01for memory formation and for the
• 07:05storage of that information.
• 07:07Persistent strengthening of the synapse,
• 07:09which leads to long lasting increase in
• 07:12signal transmissions between neurons
• 07:14again is called Long term Potentiation.
• 07:17It follows high frequency stimulation
• 07:19of the synapse and it's one of
• 07:22the major cellular reactions that
• 07:24underlies learning and
• 07:25memory. And when a synapse has been
• 07:28affected by Long Term Potentiation,
• 07:30you see a mark of that. That is,
• 07:33the spine of the dendrite gets thickened.
• 07:35And when you see thickening
• 07:37of the dendrite spine,
• 07:39you know that a memory has been
• 07:41laid down in that synapse.
• 07:43So Long Term Potentiation is one
• 07:45of the several phenomena which
• 07:47produce synaptic plasticity,
• 07:49the ability of chemical synapses
• 07:50to change their strength.
• 07:52Chemical neurotransmitters,
• 07:53again we've shown before,
• 07:55are released from the Axon.
• 07:56They activate post synaptic
• 07:58receptors on the dendrite.
• 08:00They're followed by an influx of
• 08:02electrolytes called sodium and calcium,
• 08:04and the rise of calcium inside
• 08:06the cell is the most critical
• 08:08trigger for long term potentiation.
• 08:11So this is how memory works.
• 08:13It's how nerve cells talk to each other.
• 08:15So multiple studies have demonstrated
• 08:17the role of changing the strength
• 08:20of a synaptic connection to
• 08:21the laying down of memories.
• 08:24Long Term Potentiation is the process by
• 08:26which these connections are strengthened,
• 08:29and Longterm Potentiation
• 08:30thickens the dendritic spines,
• 08:32which indicates the laying down of memory.
• 08:35Now where does protein
• 08:37synthesis come into this?
• 08:38What is the role of protein
• 08:40synthesis in memory storage?
• 08:42So usually when we think
• 08:44of protein synthesis,
• 08:45we think of proteins being those
• 08:48essential components for our skin,
• 08:51our muscles, our bones,
• 08:52our heart, our liver,
• 08:53our lungs, our kidneys,
• 08:55all of those organs in the
• 08:56body are made-up of proteins.
• 08:58The protein has another role and
• 09:01the other role for a protein
• 09:05is the storage of memories.
• 09:07So protein synthesis is the process
• 09:09of creating protein molecules.
• 09:12It's necessary for late phase,
• 09:14long term potentiation and the
• 09:16storage of long term memory.
• 09:18So we need these proteins
• 09:19to have long term memory.
• 09:21So the way in which the proteins
• 09:23are created are from amino acids.
• 09:25We have 20 amino acids in our body,
• 09:2711 are produced by our body,
• 09:29but nine have to come from our diet.
• 09:30They're called the essential amino acids.
• 09:33So we're going to talk about transcription,
• 09:35which is the process by which
• 09:37the messenger RNA template
• 09:39is transcribed from the DNA,
• 09:41the gene inside the nucleus.
• 09:43Translation is a process by which
• 09:45amino acids are linked together on
• 09:48the messenger RNA to create proteins.
• 09:51So transcription,
• 09:52the definition of the transcription,
• 09:54is a process in which information
• 09:56is rewritten.
• 09:57So when Watson and Crick first identified
• 10:01the double Helix here back in 1953,
• 10:05they learned several things.
• 10:07One of them,
• 10:07the double Helix.
• 10:08The 2nd is that what bonded
• 10:11those double Helix together were
• 10:13for nitrogen containing nuclear
• 10:16bases and they are cytosine,
• 10:19guanine,
• 10:19adenine and thymine.
• 10:20So not only are those the
• 10:23important neural bases,
• 10:25but Watson and Crick realized that wherever
• 10:28they found adenine in DNA there was Thymine,
• 10:31wherever they found cytosine in DNA,
• 10:33there was guanine.
• 10:34So they realized that these bases were
• 10:37together and the base pairing rule
• 10:39is the essence of the genetic code.
• 10:42So the way in which DNA
• 10:45replicates itself when a
• 10:46cell divides and you need more DNA.
• 10:49If the mother DNA has adenine on a site,
• 10:52the daughter DNA will have thymine.
• 10:54If the mother DNA has cytosine at a site,
• 10:57the daughter DNA will have wanting.
• 11:00So that base pairing rule
• 11:03allows replication of DNA,
• 11:05but the same base pairing rules allows the
• 11:10DNA to transmit the genetic code to the RNA.
• 11:13The only difference is on RNA you
• 11:16have uracil as opposed to thymine.
• 11:18So if the DNA has adenine,
• 11:20the RNA will have uracil.
• 11:23If the DNAA cytosine,
• 11:25the RNA will have guanine.
• 11:27So you need the genetic
• 11:29code is found in the DNA,
• 11:31but that code has to be transmitted to what's
• 11:35called messenger RNA to produce proteins.
• 11:38So the genetic code,
• 11:40each amino acid is coded for
• 11:45by three RNA nuclear bases.
• 11:47And this genetic code not
• 11:49only codes for amino acids,
• 11:51but it codes for starting the process
• 11:53and it codes for ending the process.
• 11:55So the structure that has a shopping cot
• 11:58full of amino acids is called the ribosome.
• 12:02So the ribosome comes by,
• 12:03looks down on the messenger RNA
• 12:05and sees uracil, uracil, uracil.
• 12:07The ribosome knows I have to
• 12:09need to put down phenylalanine.
• 12:11If the ribosome seems uracil uracil adenine,
• 12:14they cut down leucine.
• 12:16If they say see uracilocytosine adenine,
• 12:18they put down cellarine and so forth until
• 12:21they go through all 20 of the amino acids.
• 12:23And again,
• 12:24the code also tells the ribosome to
• 12:27stop the process tells them to start,
• 12:29tells them what amino acids to put down,
• 12:31and then tells them when to stop.
• 12:34So translation is the process in which
• 12:37proteins are synthesized in cells after
• 12:40the transcription of DNA to messenger RNA.
• 12:43It's the way in which genes are expressed,
• 12:47and the messenger RNA is decoded
• 12:49on a structure called the ribosome
• 12:51to produce an amino acid chain,
• 12:53which is then folded into a protein.
• 12:56So the synthesis of specific proteins
• 12:59is what determines whether a synaptic
• 13:02or memory process remains transient or
• 13:05becomes persistently stored in the brain.
• 13:08So we need this protein synthesis
• 13:10process to occur if we're going
• 13:12to be able to store memories.
• 13:14So proteins either strengthen A
• 13:16preexisting synaptic connection
• 13:17or form new connections.
• 13:19Proteins can be synthesized locally
• 13:21in nerve cells and what are called
• 13:23the dendrites in response to
• 13:25changes in synaptic plasticity.
• 13:26So if we talk about the memory process,
• 13:29a key feature of it is the synthesis
• 13:32of proteins to allow long term memory.
• 13:35So proteins are as important to the
• 13:37preservation of memories as they are to
• 13:40the construction of organs in the body.
• 13:42These proteins must be programmed
• 13:44by DNA to preserve memories,
• 13:46and these proteins connect
• 13:48with strengthened synapses to
• 13:50lay down and store memories.
• 13:53So how is memory constructed?
• 13:56So memory is not a literal
• 13:58reproduction of the past,
• 13:59but it's a constructive process in
• 14:01which bits of pieces of information from
• 14:04various sources are pulled together.
• 14:06So constituent features of a memory
• 14:08are distributed widely across
• 14:10different parts of the brain.
• 14:12No single location contains a memory that
• 14:16corresponds to a specific experience.
• 14:19So retrieval of past experience involves
• 14:22a process of patent completion,
• 14:24and the disparate features that constitute
• 14:27an episode must be linked or bound
• 14:31together in a process we call encoding.
• 14:34So memory is not a unitary
• 14:36faculty of the mind,
• 14:37but it's composed of multiple
• 14:39systems that have different operating
• 14:41principles and different neuro anatomy.
• 14:44There's conscious declarative
• 14:45memory about facts and events,
• 14:47and that's expressed through recollection
• 14:49as a way of modeling the external world.
• 14:52But there's also unconscious non
• 14:54clarative memory ability such
• 14:56as skills and habit learning,
• 14:59and that's expressed through performance.
• 15:02So memory is also needs to be consolidated.
• 15:05So a newly formed memory needs to
• 15:08undergo a transformative process,
• 15:10becomes stronger and more resilient over
• 15:13time until it's insensitive to disruption.
• 15:16So consolidation of many types of memory
• 15:19first depends upon hippocampal process.
• 15:22Hippocampal processing during
• 15:23the first few weeks,
• 15:25but subsequently needs to become
• 15:27independent of the hippocampus.
• 15:29So memory consolidation again
• 15:32requires RNA and protein synthesis.
• 15:35There needs to be an active
• 15:38communication between the cortex
• 15:39and the hippocampus to transfer new
• 15:42memories in the hippocampus to long
• 15:45term memories stored in the cortex.
• 15:47So there needs to be an active integration
• 15:49between the cortex and the hippocampus.
• 15:52But that's during off time periods
• 15:54such as sleep,
• 15:55and that plays an important
• 15:57role in memory consolidation.
• 15:58So again,
• 15:58we need to have good sleep patterns to
• 16:01have strong memories and a healthy brain.
• 16:04So the cortex and the hippocampus
• 16:06play complementary roles in
• 16:08memory formation and storage,
• 16:09with a cortex reflecting long
• 16:11term memory and the hippocampus
• 16:13reflecting short term memory.
• 16:15Now we also have found out that
• 16:19patients with dementia have defects in
• 16:22these processes in both the synaptic
• 16:25plasticity and protein synthesis.
• 16:28So deflex and defects in memory
• 16:30storage results from pathological
• 16:33changes in the fundamental mechanisms
• 16:36undergoing longterm synaptic plasticity.
• 16:38Disruption in gene expression
• 16:40occurs in the brains of patients
• 16:43with Alzheimer's disease,
• 16:45the nucleolus,
• 16:46which is where proteins are synthesized.
• 16:48The size of that is decreased in
• 16:51postmortem studies of patients
• 16:52with Alzheimer's disease,
• 16:54and PET scans have demonstrated
• 16:56that protein synthesis is decreased
• 16:58in the frontal cortex patients
• 17:01with Alzheimer's disease.
• 17:02So this information is important
• 17:05to understanding, if you will,
• 17:08the pathophysiology or causes
• 17:10for dementing illnesses.
• 17:11So in summary,
• 17:13memories are usually immediately
• 17:15encoded in the hippocampus.
• 17:17Long term memory is stored
• 17:19in the frontal cortex,
• 17:21synapses are the essential
• 17:23nerve unit of memory,
• 17:25and memory is stored by changes in
• 17:28the strength of synaptic connections
• 17:30that we call synaptic plasticity.
• 17:33Protein synthesis,
• 17:34however,
• 17:35is also necessary for long late phase,
• 17:38long term potentiation and the
• 17:40storage of long term memory.
• 17:42Genetic DNA is just is transcribed
• 17:45to messenger RNA,
• 17:47which uses the genetic code to
• 17:50produce these proteins.
• 17:52Memories are constructed from
• 17:54pieces of information distributed
• 17:56throughout the brain and pulled
• 17:58together to create a pattern.
• 18:00So memory consolidation is a
• 18:02process in which newly formed
• 18:04and unstable memories are transformed
• 18:07into stable long term memory.
• 18:09They require a specific
• 18:11patent of connections,
• 18:12and they require RNA and protein synthesis.
• 18:16Finally, defects in synaptic
• 18:19plasticity and protein synthesis
• 18:22are seen in patients with dementia.
• 18:25So scientists have taught us an
• 18:27enormous amount about the process by
• 18:29which the brain lays down and stores
• 18:32memory in the past several decades.
• 18:34But a lot more work needs to
• 18:36be done so that we can develop
• 18:38interventions to both prevent
• 18:40and treat dementing illnesses,
• 18:42thank you very much.