‫‪Memory‬‬
‫‪Its History and our present understanding‬‬
‫(حافظه‪ :‬تاريخچه و دريافت فعلي ما ازآن)‬
‫سعيد عمادي‬
‫گروه علوم زيستي‬
‫دانشگاه تحصيالت تكميلي درعلوم پايه زنجان‬
‫سمينارهاي هفته اي علوم زيستي‬
‫‪ 14‬آبان ‪1390‬‬
Brain
Historical Milestones
Roman physician Galen (AD 129 – 199):
Argued for the importance of the brain, and theorized
in some depth about how it might work.
Galen traced out the anatomical relationships among
brain, nerves, and muscles, demonstrating that all
muscles in the body are connected to the brain through
a branching network of nerves.
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Brain
Historical Milestones
Galen's ideas were widely known during the Middle
Ages
Not much further progress came until the
Renaissance, when detailed anatomical study resumed
and combined with the theoretical speculations of
Rene Descartes (1596 – 1650) and those who followed
him.
Descartes believed that the highest cognitive
functions are carried out by a non-physical res
cogitans, but that the majority of behaviors of humans,
and all behaviors of animals, could be explained
mechanistically
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Brain
Historical Milestones
 The first real progress toward a modern understanding of
nervous function, though, came from the investigations of
Luigi Galvani (1737 – 1798), who discovered that a shock of
static electricity applied to an exposed nerve of a dead frog
could cause its leg to contract.
 Since that time, each major advance in understanding has
followed more or less directly from the development of a
new technique of investigation.
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Brain
Historical Milestones
 Until the early years of the 20th century, the most important
advances were derived from new methods for staining cells.
 Particularly critical was the invention of a staining method by
Camillo Golgi (1843 – 1926), which (when correctly used) stained
only a small fraction of neurons, but not in their entirety,
including cell body, dendrites, and axon.
 Without such a stain, brain tissue under a microscope appears as
an impenetrable tangle of protoplasmic fibers, in which it is
impossible to determine any structure.
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Brain
Historical Milestones
 In the hands of Camillo Golgi, and especially
of the Spanish neuroanatomist Santiago
Ramon y Cajal (1852 – 1934), the new stain
revealed hundreds of distinct types of
neurons, each with its own unique dendritic
structure and pattern of connectivity.
 Neuron Doctrine
Drawing by Camillo Golgi of a hippocampus
stained with the silver nitrate method
Drawing by Santiago Ramon y Cajal of two types6 of
Golgi-stained neurons from the cerebellum of a pigeon
Brain
Historical Milestones
 Charles Scott Sherrington (1857 – 1952) is a scientist best
known for his work on how the elements of the nervous
system join together functionally.
 In 1897, Sherrington introduced the term synapse.
 In the first half of the 20th century, advances in electronics
enabled investigation of the electrical properties of nerve
cells, culminating in work by Alan Hodgkin (1914 – 1998),
Andrew Huxley (1917-), and others on the biophysics of the
action potential, and the work of Bernard Katz (1911 – 2003)
and others on the electrochemistry of the synapse.
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Memory
Historical and Conceptual Perspective
 Socrates (470-399 BC)
 Human have preknowledge, certain knowledge about the
world is inborn.
 Middle of the 19th century:
 Experimental science (chemistry and physics): Began to
attract students of behavior and the mind.
 Philosophical exploration gradually replaced by psychology.
 First experiments by psychologists:
 Sense perception, but gradually toward more complex
workings of the mind.
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Memory
Historical and Conceptual Perspective
 Pioneer in experimental psychology: German psychologist
Hermann Ebbinghaus (1850 – 1909)
 He discovered two key principles of memory storage:
1.
Memories, some short-lived and retained for minutes,
others long-lived and persist for days to months
2. Repetition make memories last longer
 German psychologists Georg Elias Müller (1850 – 1934) &
Alfons Pilzecker suggested that this memory that lasts days
and weeks becomes consolidated with time.
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Memory
Historical and Conceptual Perspective
 American philosopher William James (1842 –
1910): Short term and long term memory
 Short term memory: Seconds to minutes,
essentially extension of the present moment
 Long term memory: Weeks, months, even a
lifetime.
 This distinction has proven fundamental to
understanding memory.
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Memory
Historical and Conceptual Perspective
 Russian psychiatrist Sergei Korsakoff (1853-1900): First description
of a memory disorder (Korsakoff ’s syndrome).
 Memory impairment provide a great deal of useful information: The
study of amnesia showed that there are multiple kinds of memory.
 Charles Darwin (1809-1882):
 Mental characteristics have continuity across species.
 Human mental capabilities have evolved from those of simpler
animals.
 Inspired by these ideas Russian physiologist Ivan Pavlov (1849-1936)
and American psychologist Edward Thorndike (1874-1949)
developed animal models for studying learning.
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Memory
Historical and Conceptual Perspective

Classical conditioning:

Association of two events (sound of a
bell and the presentation of food):
Animal salivate whenever the bell
sounds, even in the absence of food.

The animal has learned that the bell
predicts the coming of food.

Instrumental conditioning:

Association between a correct
response and a reward, or an incorrect
response and a punishment that
follows the response, and in this way
gradually modifies its behavior.
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Memory
Historical and Conceptual Perspective
 Laboratory-based learning psychology: behaviorism.
 Behaviorists, led by the American John B. Watson (1878-1958)
 Behavior could be studied with the same rigor as other natural
sciences
 Studying only observable stimuli and responses:
 Behaviorists lost sight of many other interesting and important
questions about mental processes such as those within the brain that
underlie: perception, attention, motivation, action, planning, and
thinking, as well as learning and memory.
 Behaviorism: Dominant in studying learning and memory early in
the 20th century, especially in the US.
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Memory
Historical and Conceptual Perspective
 Among researchers for whom mental processes had center stage:
Feredric C. Bartlett (1886-1969) Founder of cognitive psychology
 Bartlett studied memory by having people learn material like stories
and pictures:
 Memory: Surprisingly fragile and susceptible to distortion
 Memory retrieval: Seldom highly exact
 Retrieval: Not simply a replaying of passively stored information
 Retrieval: A creative and reconstructive process
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Memory
Historical and Conceptual Perspective
 By 1960’s, due to the work of Bartlett:
 Perception and memory depend on information in the
environment and on the mental structure of the perceiver
 Cognitive psychology: Not only stimuli and responses but the
processes that intervene between a stimulus and a behaviorprecisely the domain ignored by behaviorists
 Cognitive psychologists:
 Flow of information from the eye to its internal representation
in the brain for eventual use in memory and action
 Internal representation: Take the form of a characteristic
pattern of activity in particular groups of interconnectd cells in
the brain
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Memory
Historical and Conceptual Perspective

Biological Revolutions in the 20th Century:
1.
Our understanding of how cells function in molecular terms which
expanded considerably after discovering of the DNA structure by James
Watson (1928 - ) and Francis Crick (1916 – 2004).
2.
Systems component of biological revolution: instruments such as PET
and functional magnetic resonance enabled scientists to study brain
processes during cognitive activities.

There is now two approaches in the studying the biology of memory:
1.
At the nerve cells level: cellular and molecular mechanisms of memory
storage (neurobiology of memory)
2.
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At the level of brain structures, circuitry and behavior: neural systems
Memory
Historical and Conceptual Perspective

Where memory is stored?

Actually the same question has historically been arisen about other
mental functions too.

Two viewpoints:

There are specialized areas in the brain for functions such as
language, vision, etc.

Different function are not localized, instead they are the result of
global and integrated activities of the brain.

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Now the first view is predominantly accepted by neuroscientists.
Memory
Historical and Conceptual Perspective




Karl Lashley (1890-1958):
Pioneer in localizing memory.
His conclusions:
Actually no specific location in the cortex but memory impairment
for the maze habit correlated with the size of cortex removed:
formulated the law of mass action for memory impairment
 More experimental works in the following years led scientists to
arrive at different understanding of Lashley’s results:
 Lashley’s maze-learning task was not suitable for the localization of
memory because the task depended on different sensory and motor
capabilities
 He focused only on cerebral cortex and did not explored region
below the cortex region (subcortical regions)
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Memory
Historical and Conceptual Perspective
 Nevertheless Lashley showed that there is no single center in the brain
where all memories are permanently stored: many parts of the brain must
participate in representation of memory.
 Early response to lashley’s challenge about the locus of memory came from
Donald O. Hebb (1904-1985), a psychologist at McGill University
 He suggested that assemblies of cells, distributed over large areas of
cortex, work together to represent information.
 This insight came to be seen as one of the key principles of information
storage in the brain.
 The modern view:
 Memory is widely distributed but different areas store different aspects of
the hole and there is little redundancy or reduplication of function
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Memory
Historical and Conceptual Perspective
 Cerebral cortex divisions:
1. Frontal lobe: Planning and Voluntary movement
2. Parietal lobe: Sensations of the body surface and
spatial perception
3. Occipital lobe: Vision
4. Temporal lobe: hearing, visual perception and
memory
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Memory
Historical and Conceptual Perspective
 First suggestions that memory might be stored in the temporal lobe:
 Wilder Penfield (1891 – 1976), working on neurosurgical treatment of focal
epilepsy.
 During surgery, weak electrical stimulations, and determined its effects on
the ability to speak and comprehend language.
 Brain contains no pain receptors, patients remained fully conscious, able to
report their experiences.
 Responses to electrical stimulations:
 “ It sounded like a voice saying words, but it was so faint I couldn’t get it”
 “ I am seeing a picture of a dog and cat … the dog is chasing the cat”
 These responses were elicited invariably only from the temporal lobes of
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the brain.
Memory
Historical and Conceptual Perspective

Stimulated by Penfield’s experiments: William Scoville (1926 – 2008)
soon obtained direct evidence that the temporal lobes are critically
important for human memory.

In 1957, Scoville and Brenda Milner (1918 - ), a colleague of Penfield
reported the extraordinary story of a patient H. M (Henry Gustav
Molaison, 1928 - ).

At the age of about 9, H. M. was knocked down by a bicycle and
sustained a head injury that led eventually to epilepsy.

H. M.’s seizures worsened over the years.

H. M.’s epilepsy was thought to have its origin within the brain’s
temporal lobe.
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Memory
Historical and Conceptual Perspective
 Scoville decided, as a last resort, to remove the inner
surface of the temporal lobe on both sides of the brain,
including a structure called the hippocampus, in an
attempt to treat his epilepsy.
 This experimental treatment did help his epilepsy, but it
left H. M. with a devastating memory loss from which he
has never recovered.
 From the time of his operation in 1953 until present day, H.
M. has been unable to convert a new short-term memory
into a permanent long-term memory.
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Memory
Historical and Conceptual Perspective
 Larry R. Squire (1941 - )
 His pioneering work in human memory helped describe for
the first time the role of the hippocampus and surrounding
cortex region of the brain in human memory.
 He has explored fundamental issues such as whether
memory is one thing or many, what brain structures are
important for memory, and what happens to memory in
disease.
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Memory
Historical and Conceptual Perspective
 Eric Kandel (1929 - )
 His groundbreaking research
revealed what happens to the brain
when memories are formed.
 Kandel explored how nerve cells
(neurons) change during learning.
 His research involving the sea slug
Aplysia and mice uncovered the
basis of short and long-term
memory.
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Memory
Historical and Conceptual
Perspective
 Using chemical techniques to produce mutations in single genes Seymour
Benzer (1921 – 2007) began to examine the effects on behavior of changing one
gene at a time, with the use of Drosophila as his animal model.
 He first identified a number of fascinating mutants that affected courtship,
visual perception, and circadian rhythems.
 Benzer then turned his genetic approach to the problem of learning and
memory storage.
 From mutants with memory defects, Benzer was able to identify several proteins
that are important for nondeclarative forms of memory storage.
 It was immediately evident that some of these proteins were the same as those
identified independently in molecular biological studies of nondeclarative
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memory
in Aplysia.
Memory
Historical and Conceptual Perspective
 Conclusions:

First there was no separation between the mind and the brain.

First philosophy: Until late in 19th century.

Then psychology.

And now biology.

Experimental studies first in psychology and more recently in biology.

New millenium: Questions posed by psychology and biology have
begun to converge on common ground
 From psychology perspective:

How does memory works?

Are there different kinds of memory?

What is their logic?
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Memory
Historical and Conceptual Perspective
 Conclusions:
 From biology perspective:








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Where in the brain do we learn?
Where do we store what is learned as memory?
Can memory storage be resolved at the level of individual nerve
cells?
If so, what is the nature of the molecules that underlie the
various processes of memory storage?
Neither psychology nor biology alone can satisfactorily address
these questions.
Common program of inquiry defined by psychologists and
biologists (Neuroscience):
How are the various forms of memory organized in the brain?
How is memory storage accomplished?
Memory
Historical and Conceptual Perspective





Conclusions:
What we know now :
Many forms of memory
Different brain structures and specific jobs
Memory: Encoded in nerve cells; depends on changes
in the strength of their interconnections, stabilized by
the actions of genes in nerve cells
 Findings about how the molecules inside nerve cells
change the connection strength between nerve cells
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