Transcript long-term memory

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Learning and Memory
I remember, therefore I am
– Chung-Chuan Lo
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Main stages in the memory processing
– Encoding: Acquisition and consolidation
– Storage
– Retrieval
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The Atkinson and Shiffrin modal model of memory (1968)
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Short-term memory capacity
• George Miller in 1950s
• The average capacity of short-term memory is seven
• The capacity is independent of the content of the items
• When digits are used for testing, this feature is referred
to as digit span
• Information is encoded in short-term memory as
chunks, not bits
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Dissociation between short-term and long-term memory
• Patient H. M. -- Normal short-term memory; Deficit in long-term memory
Temporal lobes removed (1953)
• Patient E. E. – Normal long-term memory; Deficit in short-term memory
Tumor in left angular gyrus (1999)
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Working memory
• Short-term memory + the ability to manipulate and transform the information
and use it in high level behaviors
• The contents of working memory could either originate from sensory input or
could be retrieved from long-term memory.
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Lesion leads to deficits in
visuospatial short-term
memory
Lesion leads to reduced
auditory-verbal memory
spans
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Classification of long-term memory I
Declarative / explicit memory
Accessible to consciousness and can be readily communicated or declared to others.

Semantic memory

Episodic memory

Autobiographical memory
Semantic memory
 General knowledge / factual information

Independent of context and personal relevance

May stored in the same brain regions with the episodic
In the 1970s, psychologist
memory
Endel Tulving introduced
the distinction between
episodic and semantic
Episodic memory

memory
But, are these two memory
types supported by different
neural systems?
Mental representation about 'what', 'where' and 'when'
about an event

Of all human capabilities, the one central to our
development of a unique sense of personal identity is
episodic memory.
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Classification of long-term memory II
Nondeclarative / implicit memory

Skill and habit (procedural memory)

Priming and perceptual memory
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Classical conditioning

Nonassociative learning
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Classical Conditioning
Classical (Pavlovian) conditioning

Instrumental (operant) conditioning
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Ivan Petrovich Pavlov (1849-1936): Nobel
Prize in Physiology or Medicine in 1904
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Amnesia
Types

Anterograde amnesia: a loss of the ability to create new memories after the
event that caused amnesia

Retrograde amnesia: a loss of access to events that occurred, or information that
was learned, before the onset of amnesia (caused by injury or a disease)
Causes

Neurological amnesia: caused by injury or disease. Characterized by severe
anterograde amnesia and some retrograde amnesia

Funcational amnesia: caused by emotional trauma. Characterized by profound
and transient (in some cases) retrograde amnesia but little anterograde amnesia
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H. M. and his amnesia I
He performed poorly on memory for short stories, word lists, pictures, and a wide
range of other materials. Remarkably, it was unclear that he even remembered that he
had undergone brain surgery
The severity of H.M.’s amnesia was shocking—he showed almost no capacity for
new learning. Also, the fact that the brain damage was known to be confined to a
particular region (the medial temporal lobes) added to the intrigue.
HM – The man who couldn’t remember
http://www.youtube.com/watch?v=utfv4SCDxtw
http://www.youtube.com/watch?v=IKP6tBhM2T4
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H. M. and his amnesia II
H.M.’s case ushered in the modern era of research on memory systems came
from the four aspects of his mental capacity that remained intact.
1.Formal testing identified that cognitive abilities other than memory were intact →
Memory could be separated from perception and intelligence.
2.H.M. could hold on to small amounts of information as long as he was actively rehearsing
the information. → The ability to maintain working memory was distinct from the
ability to make a lasting record in the brain.
3.H.M.’s childhood memories were relatively intact. → Although the medial temporal lobes
might be important for forming new memories, this region was unlikely to be the final
storage site for memory.
4.Fourth, H.M. had an intact ability to acquire new motor skill learning (Milner, 1962). →
Memory is a dissociable cognitive capacity and that day to day memory was supported
by brain structures that differed from those that supported the acquisition of
motor skills.
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Hippocampus – Animal studies I
Damage to the hippocampus and parahippocampal region produces anterograde
amnesia
→ The hippocampal memory system ordinarily supports the declarative memory for
both episodic semantic memory.
Amnesia resulting from damage restricted to the hippocampus and parahippocampal
region is highly selective in four important ways
1. Perceptual, motor, and intellectual functions are intact.
2. Memory acquired long before the onset of amnesia is typically intact.
3. The capacity for immediate memory is typically intact in amnesic patients, and, just as
in the case for healthy individuals.
4. The various forms of memory that are supported by brain systems outside the
hippocampal memory system are intact in amnesic patients.
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Hippocampus – Animal studies II
Delayed nonmatching to sample task

When the delay is only a few seconds, monkeys with experimental lesions that
include the same medial temporal lobe structures damaged in H.M. (including the
hippocampus and adjacent cortices) performed as well as normal monkeys
(Mishkin, 1978).

As the delay was increased, the monkeys became progressively more impaired.
Damage limited to the hippocampus, or to its major connections through the fornix,
produces only a modest impairment. In contrast, damage that includes the
adjacent cortices produces severe amnesia.
Using this animal model, investigators were able to identify the structures of the
medial temporal lobe critical to supporting declarative memory
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Hippocampus – Spatial memory
Many studies in rats have demonstrated
that damage to the hippocampus results in
deficits in a variety of spatial learning and memory
tasks.
Rats with hippocampal damage are severely
impaired in the water maze task.
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Amygdala – the contribution to emotion
The amygdala contributes to emotion in several ways, including mediating
emotional influences on attention and perception and regulating emotional
responses.
1. The amygdala supports the acquisition of emotional dispositions toward stimuli.
This kind of memory includes preferences and aversions.
2. The amygdala mediates the influence of emotion on the consolidation of memory
in other memory systems
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Amygdala – Acquiring emotional dispositions to stimuli I
Fear conditioning experiment:
Conditioned fear elicited by the tone is assessed by measuring autonomic responses,
such as changes in arterial pressure, and motor responses,
such as stereotypic crouching or freezing behavior.
Rats with lesions in the BLA (basolateral amygdala complex) show dramatically reduced
conditioned fear responses to the tone in measures of both autonomic and motor
responses but still show normal unconditioned fear responses to the shock itself.
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Associative Learning & Nonassociative learning
Associative Learning:
 Formation of associations among stimuli and/or responses.

Subdivided into classical conditioning and instrumental (operant) conditioning.
Nonassociative Learning:
 Three examples of nonassociative learning have received the most
experimental attention: habituation, dishabituation, and sensitization
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Vertebrate studies: Long-term potentiation
Long-term potentiation (LTP):
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Defined as a persistent increase in synaptic strength

Typically measured by the amplitude of the EPSP (excitatory post-synaptic
potential) in a follower neuron
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First demonstarted in 1973 by Timothy Bliss and Terje Lomo demonstrated LTP
in the hippocampus of an anesthetized rabbit.
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Now known to occur in the cerebellum, neocortical regions, subcortical regions
such as the amygdala, mammalian peripheral nervous system, the arthropod
neuromuscular junction, and the Aplysia sensorimotor synapse.
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No universal mechanism exists for inducing LTP.
LTP at the CA3–CA1 synapse in the hippocampus
Two time domains:
 An enhancement that persists for about 90 min → early LTP (E-LTP).
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An enhancement that persists for periods of time greater than about 90 min
→ late LTP (L-LTP)
Cooperativity, Associativity & Input specificity
The CA3-CA1 LTP are classic with the following properties:
 Cooperativity
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Associativity
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Input specificity
Cooperativity & specificity
Associativity
Hebbian learning
Donald O. Hebb (1904-1985)
Hebbian theory:
When an axon of cell A is near enough to excite cell B and repeatedly or
persistently takes part in firing it, some growth process or metabolic
change takes place in one or both cells such that A's efficiency, as one of
the cells firing B, is increased
Neurons that fire together wire together.
Hebbian rule & LTP
Could the classical properties of LTP all be consequences of synapses that obey a
Hebbian rule?
Possibly so if a critical amount of postsynaptic depolarization were a necessary
condition for inducing LTP in active synapses.
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Cooperativity → enough input fibers need to be stimulated to produce the critical
amount of postsynaptic depolarization.
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Associativity → strong input caused sufficient depolarization of the postsynaptic
membrane during the presynaptic activity in the weak input.
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Input specificity → LTP was induced only in those inputs to a neuron that were active
at the same time that the cell was sufficiently depolarized by the strong input to that
neuron.
Mechanisms of Long-Term Potentiation
Induction of LTP depends on an increase in the intracellular concentration of calcium
ions ([Ca2+]i) in some key compartment of pre- and/or postsynaptic cells (Bliss and
Collingridge, 1993; Johnston et al., 1992; Nicoll and Malenka, 1995).
Two major pathways that have been studied extensively
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Calcium influx through ionotropic GluRs, especially NMDA receptors
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Calcium influx through voltage-gated calcium channels (VGCCs).
NMDA receptor and LTP
The NMDAR has two properties that immediately suggest the nature of its role in LTP
induction at Hebbian synapses:
1.NMDARs are permeable to Ca2+
2. The channel permeability is a
function of both pre- and
postsynaptic factors.
→ Channel opening requires the
neurotransmitter glutamate
(presynaptic condition)
→ Sufficient depolarization to
remove the magnesium block (post
synaptic condition)