HMB200 Lecture

The Learning Brain and

Changing Behaviour 2

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 Get to know my students
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• Engineering + neuro is a great combo!
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• You want to go skydiving?? Not me…

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Can you trace
the star WITH
YOUR MOUSE
UPSIDE
DOWN?
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

4
 Where is memory in the brain?

Movement Touch

There is evidence of
functional specialization in
the brain, but what about
Vision memory??

Language

Hearing
 Lashley spent a large part of his career searching for the location of
memories in the brain. He trained rats to solve spatial puzzles and then
lesioned parts of the cortex to discover which lesions were associated with
memory loss. Multiple experiments demonstrated that memory loss was
associated with the extent of a lesion and not its specific location.

“The conclusion is justified, I believe, by such considerations and is

supported by electrical studies, that all of the cells of the brain are
constantly active and are participating, by a sort of algebraic summation,
in every activity. There are no special cells reserved for special
memories.” (Lashley,1950, p. 26)

His ideas that the memories do not have a dedicated place in the brain but
arise as a result of interaction of electrical activity from multiple regions
was very influential. The memory was conceptualized as a distributed
process depending on activity within the entire cortex.
Until the case of patient H.M.

Karl Lashley
(1890-1958)
 Brenda Milner William Scoville

Drs Milner and Scoville revealed

“What [Dr Scoville] learned
that the temporal lobe structures
about me helped others, and
(note: not only the hippocampus)
I’m glad about that“
are involved in forming and
Henry Molaison
retrieving memories of every day
events (episodic memories).

Patient H. M. was the most famous case in the history of neuroscience. His life was a continuous source of new knowledge and
inspiration for multiple studies that led to ground breaking discoveries in memory research.

A bicycle accident at age 7 caused Henry to experience seizures which became worse as he got older. At 27 his seizures could not be
controlled by medication and prevented him from leading a normal life. Offered an experimental treatment by Dr. Scoville, parts of his
temporal lobe structures including the hippocampus (bilaterally) were surgically removed.

Since the day of his surgery, Henry could not form new memories (or so it seemed).

Henry also had some retrograde amnesia. He had an impairment in retrieving recent pre-operation memories (up to a
few years before the surgery). However, many of his childhood memories remained intact (or so it seemed).
 Key discoveries inspired by H.M.
Short term vs. long term memories

Henry’s working memory (a capacity to attend to

information and maintain it for a short duration)
was intact. He could maintain a memory of a 3-
digit number for up to 15 min if he rehearsed it.

However, if his attention was diverted he would

forget not only the number but the entire
task of remembering it.

Working memory performance can be enhanced

with training and the regions that are associated
with improved working memory are the
prefrontal and parietal cortices. Striatal DA
PPC – posterior parietal cortex
signaling mediates working memory capacity. MFG and SFG – gyri, parts of the prefrontal cortex
Str - striatum
Immediate (or working) memories are distinct
from long-term memories in their function and
underlying brain circuitry.
 Key discoveries inspired by H.M.
Anterograde Amnesia

It seemed that Henry could not form new long-

term memories. Example: he did not recognize
his Drs day after day = Anterograde Amnesia
Remote Recent New
Henry’s representation of everyday events
existed only in present time. He introduced
himself every time to Drs. Milner or Corkin for
Retrograde Anterograde
~ 30 years. As he aged, he was surprised to
amnesia amnesia
see the person in the mirror.
(graded) Surgery

Initial Theory: Hippocampus (MTL) is involved

in forming long-term memories.

"It's a funny thing – you just live and learn. I'm living and you're learning.“ – H.M.
Try to trace the star – but with your mouse upside down

Henry showed normal learning curve for this task

When asked if he remembers doing the task:

“No, never”

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 Key discoveries inspired by H.M.
Summary of Henry’s Anterograde amnesia
New declarative Visuomotor
memory Who are we?
Henry’s perceptual function and intelligence were “I don’t know”
fully intact, and his personality did not change. Henry’s
attention was not affected.

AND Dr. Milner discovered that he could learn a new

visuomotor task normally.

In addition, priming, habituation and sensitization was

normal, as was some forms of conditioning

This led to the (better) theory that there must be

multiple memory systems in the brain.

Each depends on processing within different brain

regions.

Henry showed severe impairment in Declarative memory.

Henry showed few impairments in Non-Declarative memory.
Learn and show “How”
Learn and Know “That”

“like waking from a dream ... every day is alone in itself...” – H.M.
 Key discoveries inspired by H.M.
It is concluded that the anterior hippocampus and
hippocampal gyrus, either separately or together,
are critically concerned in the retention of current
experience. It is not known whether the amygdala
plays any part in this mechanism, since the
hippocampal complex has not been removed alone,
but together with uncus and amygdala. (Scoville
and Milner, 1957)

The hippocampus became the central structure

in the memory research. The field took two
directions. 1) Human research with the medial
temporal (MTL) lobe patients established the role of
the hippocampus and MTL for declarative
memories. 2) Lesion and electrophysiological
studies demonstrate HOW the hippocampus
processes declarative memories (or, in animals,
spatial learning and memory)

In the recent years, the findings from the two

streams are brought together to demonstrate a
unique role of the hippocampus to integrate
information from multiple sensory inputs to form
declarative memories from everyday experiences.
Common Nomenclature for the 2 Memory categories

Declarative Non-Declarative
Explicit Implicit
Fact Skill
Knowing that Knowing how
Conscious recollection Unconscious habits
Elaboration Integration
Memory with record Memory without record
Autobiographical Perceptual

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 Key discoveries inspired by H.M.
Retrograde Amnesia
Remote Recent New
Henry’s Retrograde amnesia of past events
was graded: he could recall his friends, job,
political events that happened > 3 years prior
Retrograde Anterograde
his surgery.
amnesia amnesia
(graded) Surgery
Henry seemed to remember many aspects of
his childhood and all facts of the world he had
learned (his IQ remained normal)

Initial Theory: Hippocampus (MTL) is involved

in both forming memories and, at least for a
time, recalling memories.

Initial Theory: Memories initially depend on

the hippocampus MTL but then with time
become hippocampus-independent, relying on
the storage within cortical networks.

Long-term memories may undergo

reorganization and depend on networks
different from recent memories.

"It's a funny thing – you just live and learn. I'm living and you're learning.“ – H.M.
 How memories “transferred” to the cortex?

Long-term
memory

There is a theory that suggests that if the learning event is strong or repeated (e.g. recalled enough) then it forms
a long-term memory by plasticity based processes within the cortical modules that represent the individual
components (sensory, emotional etc) – and becomes independent of the hippocampus over time (see right figure)

This theory explained why Henry could remember his childhood! BUT – see next section – there are doubts.

(analogy is e-LTP to L-LTP - with L-LTP forming between the cortical modules to consolidate the “engram”).

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https://www-nature-com.myaccess.library.utoronto.ca/articles/s41583-019-0150-4#Fig1
https://tinyurl.com/hmb200qa
16
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

17
 Two kinds of Declarative memories

Henry’s Retrograde amnesia of past events

What is the
seemed to have at least two somewhat Tell us about one
capital of
different components. day on the job.
France?
“I was on the
“Paris”
Henry’s memory of general facts about the assembly line…”
world, and even of himself, seemed far better
than his autobiographical memory (though he
did seem to show some autobiographical
memory) he could recall his
friends, job,
This aligned with the theory that episodic
and semantic memories are distinct. political events
that happened,
facts about the
world and thus his
IQ remained
normal.
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 Episodic vs. Semantic Memory

Episodic memories refer to knowledge “about temporally dated episodes or

events, and temporal-spatial relations among these events” (Tulving, 1972, p. 385).

It is the conscious representation of an event (episode) that has occurred only once.

Information about the content is based on sensory information (e.g. I see a cat in front of
me + any other sensory info occurring at that time), location (where you are, locally, which
room etc) and other context such as internal processing (e.g., emotional state, time)

It is believed that the episodic memories are evolutionary youngest. It is still debated
whether we should call memories in animals episodic or episodic-like.

Episodic memories allow you to remember your personal experiences, semantic cannot.
Episodic memories involve YOU, semantic memories do not.
Episodic memories require conscious awareness and usually include a very rich array of
components that represents what happened.
 A schematic of how episodic memories are encoded

“Binding” theory proposes that various aspects of an experience (e.g. sensory, contextual, emotional inputs) are
“bound” together and through plasticity form an “engram” which defines the memory.

The hippocampus receives information the perirhinal cortex (blue), which receives information about the items in an event from the ventral
‘what’ stream (faded blue); the amygdala (dashed outline), which provides information about the emotional aspects of the event; and the
parahippocampal cortex (green), which receives spatial information from the dorsal ‘where’ stream (faded green).

The hippocampus may be the structure that binds or integrates all of these inputs cooperatively or
associatively by its unique structure and function. It may support complex or high-resolution bindings. This
aligns with neurocomputational models that propose that the hippocampus supports memory via a process of
pattern separation and completion.
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https://www-nature-com.myaccess.library.utoronto.ca/articles/s41583-019-0150-4#Fig1
 Evidence that episodic memories are always hippocampus dependant

Morris Moscovitch’s research suggested that long-term episodic memories

ALWAYS need the hippocampus.

He studied MTL lesioned subjects and found that the remote “episodic memories” Morris Moscovitch
they had lacked the rich perceptual detail found in controls. UofT, Psych Dept

In the case of Henry, while he did seem to remember events of his childhood and
early adulthood, Dr. Moscovitch’s research (with several other MTL lesion
patients) suggested that these memories of unique events contained far fewer
details. Thus, the removal of MTL tissue from Henry's brain left him devoid of rich
autobiographical memories but not semantic memories.

Susan Corkin (referring to Henry’s autobiographical memories): "The interesting

and important thing scientifically about these stories was that he would give you
the gist of them, but they were never linked to a specific time and place. You and
I can say what we did on our last birthday. But Henry could never remember what
else happened. There were no connections, no associations for him in that way."
 Hippocampus encodes all declarative, but may remain necessary to retrieve episodic
We now know that the medial temporal-lobe structures are engaged in the initial encoding, storage, and retrieval of
all declarative memories (episodic and semantic). Then, during the process of consolidation, semantic memories
become permanently established in the cortex while episodic, autobiographical-memory traces continue to depend
on medial temporal-lobe structures indefinitely.

A family camping trip that one might remember in full detail, including emotional and perceptual elements would be
an example of an episodic memory. It could also be “semanticized” to maintain the gist, but not the details.

Two summers ago my parents and I went

camping to Algonquin park. We slept in a big
orange tent close to the lake. One morning I
Camping is a woke up early and went to the lake and there
family-bonding was a huge moose. I was so surprised! It was
watching it for 10 min. Even though it was so
experience big it was super quiet. I didn’t even notice how
cold it was, I wasn’t wearing a sweater. We had
marshmallows the previous night but I didn’t
like them. They were too sweet.

Semantic memory and/or “the gist” Detailed episodic memory

No temporal or contextual references Mental time-travel, self-referenced
Always hippocampus dependent
Initially hippocampus dependent – then cortex only
 Given time and practice, the cortical module become bound together

The cortical activity patterns that define experiences are co-activated with
hippocampus/MTL. Declarative memories are “bound” by the MTL/cortical
connections.
Rich, autobiographical, episodic memories may
Semantic memories (simpler associations) become
always be dependent on MTL to reactivated all the
stored only in cortex, independent of MTL. cortical modules

Hippocampus creates “Index”

A sparse, specific&representation
Frankland Bontempi, 2005of the sensory pattern
(“pattern completion” may be the mechanism to recall the memory from a single sensory clue 23
 Key discoveries inspired by H.M.
Summary (of Henry’s retrograde amnesia)

Tell us about
What is the
your trip to Paris.
capital of
?
France?

Full, rich, episodic memories The “gist” and/or semantic memories

 Explicit Memories Implicit Memories
Memory with awareness Memory without awareness
Hipp/MTL important Hipp/MTL not necessary

Stored
here (+/- MTL):

Hippocampus/cortex
Other brain regions
Formed
here:
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https://tinyurl.com/hmb200qa
26
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

29
A Memory Engram replicates the brain activity
observed during sensation/ perception

Memory – similar cortical sites activated

How is that engram “BOUND” together?

https://www.youtube.com/watch?v=lkegFMnGY74
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 Hippocampal structure/function
Supplemental – for your deeper learning
• Pattern separation, pattern completion, auto association – all network
functions mediated by the structure of the different parts of hippocampus
(and DG).
• Much is unknown still, but consensus view is this is what mediates episodic
memories

https://www.youtube.com/watch?v=lkegFMnGY74 33
 Examples of pattern separation and pattern
Pattern separation
Pattern completion
MTL: concept cells
Epilepsy patients are often implanted with intracranial
electrodes before the lesion surgery to identify the
origin of seizures. Recordings of APs of individual
neurons has become a powerful tool to analyze the
cognitive function of individual neural activity.

Example: A single MTL neuron responds to Jackie

Chan images, written name and audio but not to images
of other actors. Note – not any specific sensory input,
rather the “concept” or identity of Jackie Chan

These neurons exemplify the extreme of integration.

They capture (through associative LTP of inputs??) all
of the “contextual” bits of one single concept (in this
case a person) – and any one bit can reactivate the
same concept.
 Hippocampus: Remembering the past and imagining the future

Many researchers noticed that amnesiac patients not only couldn’t recall
their past but had impaired ability to imagine the future.

Patients with bilateral hippocampal lesion and matched controls were

asked to imagine a scenario given certain verbal cues (e.g., “Imagine
you're lying on a white sandy beach in a beautiful tropical bay”). Their
imaginary stories then were scored based on the “episodic” richness of
the detail (e.g., sensory, spatial or emotional description) and spatial
integrity. The patients had dramatically reduced scores compared to
controls, suggesting that inability to remember episodic memories and to
imagine episodic events may rely on the same circuitry.
 Summary – Hippo/MTL as memory integrator
Encoding of perceptual, motor and cognitive information initially occurs in
primary and associative cortical areas. Connections to the hippocampus
“binds” the info, the “engram” represents the various features of the
experience.
• Partial reactivation triggers full memory activation
• Successive reactivation strengthens the connections (cortical – cortical
and/or cortical – hippocampus)

• Some memories (semantic) may become independent of the hippocampus

• Episodic memories may remain dependent on hippocampus (full rich
multicomponent memories may rely in the complex patter completion
function of the hippocampus)

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https://tinyurl.com/hmb200qa
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Break: Pajama Day!!! Let’s turn our camera and show
your favourite pajamas!
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

40
 Rodent hippocampus

There are obviously challenges in measuring “declarative” memories in

non-human animals. However, what was already known was that the
hippocampus was important for “spatial” learning and spatial or “cognitive”
maps. This suggested it plays an “integrator” role in rodents as well.
Hippocampus required for “contextual” fear conditioning

Infusion of muscimol (which blocks the activity) into the

hippocampus disrupts acquisition/consolidation of
contextual fear (Context) but not auditory tone fear (CS)
42
 Hippocampus lesion = “relational” or spatial version of water maze impairments

OR – if visible flag at the platform

With visible cues on the walls

of the hippocampus

Hippocampus lesion – impairments in spatial Hippocampus lesion – rats do learn non-

lmemory (~declarative) version declarative (skill leaning/habit) version

43
https://biology-forums.com/index.php?action=gallery;sa=view;id=21956
 Spatial Memory in Rats

Trial # 1 Trial # 8

44
 Place Cells in the Hippocampus
In 1970s Jonathan Dostrovsky (Master’s student) in O’Keefe’s lab
discovered that activity of hippocampal neurons is driven by space/location
specific information.
They noticed that a single neuron fired when (and only when) a rat was in a
particular location in the environment.
The place associated with neuron’s activity would be called a place field,
and these neurons are called place cells. Multiple place cells have their
place fields distributed across the entire environment.

Experimental box where

Neurons in the CA1 or CA3
the rat is running around

John O’Keefe
UC London
Received PhD
from McGill U

When the rat travels in the area of the box indicated by

coloured circles a single neuron fires APs and so we
define that location as the place field for that place cell
Place Cell Recording

46
Two important characteristics of place cells:
1. The firing patterns are “stable” over time. Same pattern reappears in same environment subsequently.
2. The firing patterns are different (and independent) in different environments. This is called remapping.
These characteristics (and many other discoveries!) suggest that the place cells (hippocampus) firing patterns not
only represent places and spatial contexts, but also the memory of that environment.

Box 1 Box 1 Box 2

Time
 Place cell encode more than just place – also context

Hippocampal place cells may remap in the same environment/place with different perceptual features (wall
colour, texture, odour, box shape, illumination) and also based on internal representations (emotional stimulus).
These findings indicate that the hippocampus encodes more than spatial information (likely the entire context).

Hippocampal place cells remap in the same environment under

different illumination conditions. Red circle indicates a place field
of a place cell that fires AP in a box only when lights are on.

A rat placed in the same environment but with a different odour (Lemon vs.
vanilla) permeating shows some place cells remapping, and some staying
stable. This indicates some place cells may be encoding just “place” and
some “context” https://www.jneurosci.org/content/23/26/8827

Some place cells show remapping after fear conditioning. The place cell has
its place field at the south part of the box. After conditioning (right image) it
remaps to a new position. https://www.nature.com/articles/nn.2648
 A spatial map of the world in the hippocampus
If one records the electrical activity of a number of place cells it is possible to
predict where the animal is in its environment. In this manner the
hippocampus is thought to constitute a cognitive map of the animal’s
surroundings. O’Keefe’s demonstration of place cells provided the first
evidence for a neural representation of the environment that allows an
animal to move deliberately around the world. The idea of a cognitive map
was predicted earlier by the great cognitive psychologist Edward Tolman.
Kandel, Principles of Neuroscience Ch 67.

More recently it is clear that the cognitive map can incorporate entire
“contexts” and not just spatial location. It may not only be the construct to
spatial navigation, but also to episodic memories.

49
https://tinyurl.com/hmb200qa
50
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

55
 Explicit Memories Implicit Memories
Memory with awareness Memory without awareness
Hipp/MTL important Hipp/MTL not necessary

Stored
here (+/- MTL):

Hippocampus/cortex
Other brain regions
Formed
here:
56
 Remember Sammy Jankis?
• Sammy had a car accident and ended up with total anterograde amnesia.

“He could perform complex tasks (like injecting his wife with insulin) as
long as he learned that task before the accident, and kept his mind on it”

• What was his lesion?

57
Remember Sammy Jankis?

What must have been his lesion(s)? 58

 Dissociating learning and memory systems and their brain regions

Experiment (fear conditioning protocol)

1. Learning/Creating the fear memory
• Display green, blue, yellow, or red images on the screen.
• During the green images, sound a loud horn blast (the US)

59
 Dissociating learning and memory systems and their brain regions

Experiment (fear conditioning protocol)

1. Learning/Creating the fear memory
• Display green, blue, yellow, or red images on the screen.
• During the green images, sound a loud horn blast (the US)
 Dissociating learning and memory systems and their brain regions

Experiment (fear conditioning protocol)

1. Learning/Creating the fear memory
• Display green, blue, yellow, or red images on the screen.
• During the green images, sound a loud horn blast (the US)
 Dissociating learning and memory systems and their brain regions

Experiment (fear conditioning protocol)

1. Learning/Creating the fear memory
• Display green, blue, yellow, or red images on the screen.
• During the green images, sound a loud horn blast (the US)
 Dissociating learning and memory systems and their brain regions

Experiment (fear conditioning protocol)

1. Learning/Creating the fear memory
• Display green, blue, yellow, or red images on the screen.
• During the green images, sound a loud horn blast (the US)

63
 Testing for fear learning/memory
2. Then show the various colored images – one by one – and test if the
subjects show “fear” to any of them.

Fear response can be measured by galvanic skin response

(“sweating” – part of the 4Fs)

64
65
66
67
68
 Distinct Learning and Memory Systems
After conditioning, what happens?
(Assume no subjects show fear to any other image)

Fear Response to the Green Do they remember learning that the

Image? Green one is scary?

Subjects Yes No Yes No

Control

Hippocampus lesion

Amygdala Lesion

Both lesioned

69
 Dissociation: hippocampus vs amygdala

AMG
HPC

AMG
HPC

AMG
Participates underwent visual-auditory (blue) or auditory-auditory
HPC
(red) fear conditioning. CS was a neutral image or tone, US was a
loud boat horn. Skin conductance response (sweating evoked by
fear) was measured (CR) in response to CS. Bilateral AMG patient
AMG showed no CR but had intact memory of learning CS-US
HPC association. Bilateral HPC patient showed intact CR response but
no memory of learning the task. The response to stimuli that never
were paired with US was increased, suggesting a generalization.
Bilateral AMG+HPC patient lacked ability to respond to CS and had
no memory of the learning experience.
 Summary
Memento got some things right and some things wrong.
• Leonard’s condition and Sammy’s condition were nicely and accurately
portrayed (hippocampus and hippo + amyg lesion)
• Leonard stated that declarative memory and conditioning are different
(true), but wrongly stated that conditioning and habit or instinct are the
same
Declarative memory, conditioning and habit are three independent brain
processes mediated by 3 different brain regions
Hippocampus/MTL are important to encode unique events “episodes” and is
very important for complex stimulus integration (spatial) Declarative
Amygdala is important for some simple forms of classical conditioning

OK, so what about the habit region?

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 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

73
 Explicit Memories Implicit Memories
Memory with awareness Memory without awareness
Hipp/MTL important Hipp/MTL not necessary

Stored
here (+/- MTL):

Hippocampus/cortex
Other brain regions
Formed
here:
74
 N Dissociation: hippocampus vs striatum

W E

S
The rat is placed on the S arm of a plus maze. There is
a hidden food reward at end of the W arm.
At first it randomly explores, until it finds the food. With
subsequent trials, it finds the food faster and faster.
 Multiple Memory strategies to solve this task

N
Two strategies:

1. Go to the arm between the star and the

sun (spatial/place based navigation)
W (e.g. go between star and sun)
E
2. Turn left (cue independent, response-
based navigation)
(e.g. turn left)

Which strategy is better?

S
 To test which strategy, start the animal from the North arm

N
Which strategy is being used?

If the rat goes to the West arm:

• It is using the spatial/place strategy
W E (e.g. go to the arm between the star
and sun)

If the rat goes to the East arm:

• It is using response-based strategy
(i.e. turn left)
S

So what happens?
 After 8 days of training, Test from N
N

W E

S
Method: Conclusion?
Training: 4 trials per day, for 8 days always
starting from the S arm
Testing: start from N arm
 Which brain region? Test by inactivating with lidocaine
N
Lidocaine injection temporarily blocks activity

W E

S
What brain region is responsible for
navigation early in learning? Lidocaine injection in the Lidocaine injection in the
striatum had no effect, hippocampus impaired finding
most went to the W arm the reward! Fewer went
between star and sun
 After 16 days of training, test from N
N

W E

S
Method: Conclusion?
Training: 4 trials per day, for 16 days
always starting from the S arm
Testing: start from N arm
 Which brain region? Test by inactivating with lidocaine
N

W E

S
What brain region is responsible for Lidocaine injection in the Lidocaine injection in the
navigation later in learning? striatum changed their strategy! hippocampus had no effect
Cannot “turn left” so reverted to – they still “turn left”
WHY?? “between star and sun”
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 Check your understanding
You have been coming to class every day for 2 years –
exit St. George Station, same route to New College

Which brain region is most important for today’s journey?

Hippocampus Striatum
 Check your understanding
You have been coming to class every day for 2 years –
exit St. George Station, same route to New College

Today, you accidentally get off at Museum Station (first time ever)
– but you find your way to class.

Hippocampus Striatum
 Check your understanding
One day you have a stroke that damages the hippocampus.

The Next Day… YES NO

Will you be able to find your way from
Museum Station to New College?

Will you be able to find your way from

St. George Station to New College?
 Check your understanding
Suppose that instead of a hippocampus stroke, you had a
stroke that damaged the striatum.

The Next Day… YES NO

Will you be able to find your way from
Museum Station to New College?

Will you be able to find your way from

St. George Station to New College?

Be sure to answer WHY to all of these!

 Hippocampus and Striatum memory systems summary
Excellent experiment showing “double dissociation” In the maze
between 2 memory systems.
At first, the animal is randomly foraging (goal directed)
Early learning seems to be spatial “explicit” memory
reinforced by finding the reward
• hippocampus dependent
• performance suffers if hippocampus inactivated
• declarative/Episodic like???
Later learning seems to build the habit (implicit) memory
reinforced by finding the reward
• Caudate/striatum dependent
• Comes to dominate behaviour – even though it may err!
Parallel memory systems: When both memory systems
are established inactivating one, may lead to use of the
other IF that memory system is capable.
Habit memory forms:
When in the maze, Turn left
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Learning Habits (in this case a prediction)

Performance on the prediction task across the first 50 training trials is plotted on the left;
performance results on a declarative memory test are shown on the right. Amnesic patients
(AMN) initially learn the prediction task at the same rate as healthy control subjects, although
their performance on the declarative memory task is impaired. By contrast, patients with
Parkinson disease ( PD ), who suffer impairments in basal ganglia function, perform poorly on
the prediction task but perform as well as controls on the declarative memory task. PD* identifies
a subgroup of the Parkinsonian patients with the most severe symptoms. 88
https://tinyurl.com/hmb200qa
89
 Lecture 7 outline
While this lecture won't be "startlingly" good, it may just be unforgettable!
1. Learning and Memory Theories inspired by H.M. – Declarative vs. Non-Declarative
1. Short vs. long-term. 2. Long-term Anterograde Amnesia 3. Retrograde Amnesia
2. Episodic vs. Semantic Memories
3. Hippocampus and the Memory Engram
4. Hippocampus based memory research in animal models
5. Dissociating the multiple memory systems
1. Hippocampus (declarative) vs. Amygdala (conditioning). 2. Hippocampus vs. striatum (habit)
6. Amygdala and Striatum – Classical and Operant Conditioning
Great Resources to Prepare
Neural Circuitry for fear
http://www.psychologytoday.com/blog/trouble-in-mind/201201/hm-the-man-no-memory (Links to an external site.) - All
about H.M.
Meet H.M.: What happens when you remove the hippocampus? - Sam Kean (Links to an external site.)
Pattern "separation" and "completion -The Hippocampus and episodic memory (Links to an external site.)
Watch the movie "Memento" - and especially compare the characters "Leonard Shelby" vs. "Sammy Jankis"

90
 Habit formation begins with operant conditioning

Habits form when natural behaviours (e.g. goal directed foraging) become reinforced by
the consequence.

Example: I foraged in this plus maze, I found a reward – next time I will forage even more especially
between the star and sun.
As habit memory systems build: Seems like the reward is there after I turn left. Next time I will just
turn left.

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Habit memory consolidates by classical conditioning
Recall classical conditioning –
a cue comes to elicit a reflex

For habit learning, cues can come to

predict WHEN the routine (outcome -
reward contingency) is available

I.e. When in Maze → turn left

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 Amygdala
Habit memory “Engram”

Response

Recall the Fear memory engram is

the strengthened synapse between
the CS and the LA (cooperatively
strengthened by the US)

In the striatum, the “CS” comes the elicit

the behavioural “habit”
Striatum Turn left
Behaviour Consequence
CS (E.g. reward)

In the maze

The “reward” pathway serves as the “US”

to strengthen the CS – striatum synapse 93
 Memory systems of the basal ganglia

https://www.sciencedirect.com/science/article/pii/B9780128022061000350?via%3Dihub 94
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