A Brief History of Neuroscience (Mark A. Gluck, Rutgers University-Newark). August, 2020.

>> The field of
neuroscience is

an incredibly
exciting field

to be working in,

to be studying, and
to be teaching.

Many people think
of the field as

being about 50 years old.

It was in the
mid 1960s that

the first
universities began to

have academic departments

devoted to neuroscience,

graduate programs
devoted to neuroscience.

In 1969, the Society for

Neuroscience was founded.

And now 50 years later,

it has 35,000 members and

affiliate organizations in

almost 100 countries.

And much of what
we're going to be

talking about in
the course to come

this semester is
going to focus

on those last 50 years

where the field
has exploded

year by year and
decade by decade.

But these 50 years of

neuroscience didn't
start from scratch.

In fact, they
built on 2,000

years of work by
philosophers,

and doctors, and
scientists trying

to understand how
the brain worked.

So today, I want
to take you on

a very brief
15-minute tour of

those 2,000 years of

prehistory of
neuroscience.

So buckle your seat belts

and be prepared
to find out

where and how
did the study of

how does the brain
work begins.

This history
will cover the

first 2,000 or so years of

the field from about
400 BC until the 1950s.

And we'll focus
on three classes

of questions which
have predominated

over these last two
millennia as people

struggle to understand

how does the brain work.

These three classes
of questions

begin with philosophy,
functional anatomy,

and lastly, cellular
mechanisms.

And let me tell you
some of the questions

that each of these
areas have asked.

In philosophy,
the questions

that are predominated
have been,

what is the
brain good for?

Is the mind distinct

from mechanisms
of the brain?

Functional anatomy
has asked a number of

different questions
that try to localize

where in the brain
different functions occur.

Some of these
questions are,

what is the
functional role of

brain subregions
and nerves?

How can we understand and

treat different mental
health disorders?

Can localized brain
lesions tell us about

the functional
organization of the brain?

How is memory organized,

and how and where are

learned reflexes formed?

The third class
of questions

are about cellular
mechanisms,

questions such as,

what is the structure
of individual neurons?

What is the function of
neurons and synapses?

And how do neurons use

electrical signals
to communicate?

So these three classes of

questions have
emerged over

the last two millennia in

the following
approximate timeline.

So the philosophical
questions

began early on when there

wasn't a lot
of technology,

there wasn't a
lot of data from

400 BC to what
is the brain

good for to the
early 1600s

when philosophers asked,

is the mind distinct from

the mechanisms
of the brain?

Questions about
functional anatomy

emerge in the
middle period,

from the early BC,

even up through
the early 1900s,

asking the variety of

questions about how do we

localize function to

specific parts
of the anatomy.

And lastly, with
the development of

newer technologies
for looking at and

measuring and
analyzing the brain,

we see the cellular
mechanisms

have emerged
later in history.

So now you understand
the timeline,

there are going to be

10 questions that I'm
going to focus on

starting in 400 BC

and taking us
through the 1950s.

>> [MUSIC]

>> The first question
was back in Greece,

where Hippocrates
and Aristotle

argued about the question,

what is the brain for?

What is the
brain good for?

Now, Hippocrates
believed it

was the seat of
intelligence,

it was key for sensation
and perception,

and it was what was
disrupted in epilepsy.

Three things which
have still held

true even all
these years later.

Aristotle thought
the brain

was a cooling mechanism,

something like a
radiator for the blood,

and he believed the
heart, not the brain,

was the source of

rationality and
intelligence.

Well, clearly, these
two ideas turned out to

be wrong, but
to his credit,

Aristotle got many
other things right

about psychology and
philosophy in the brain,

including the fundamental
principles of

learning and the
essential role

of experience
in knowledge,

what we call empiricism.

Moving ahead in
time, Galen,

often called also
Claudius Galenus, asked,

what is the
functional role of

the brain subregions
and nerves?

Galen was a physician,

and his main day
job was working for

the Romans fixing
gladiators

who had been damaged
after battle.

He believed temperament
and bodily functions

were controlled
by the brain,

and he dissected
sheep, monkeys,

and dogs to learn more
about the body because

Roman law at that
time forbade

autopsy on humans.

Now, from these
autopsies that he did,

these dissections
on animals,

he made a number of
conclusions that

have still held
true today.

He concluded that the
hard cerebellum in

the back of the brain was

for muscle control,

while the softer cerebrum
around the top and

around the shell of

the brain was
for the senses,

and that we know
to be true.

He dissected nerves
and believed that

each nerve pathway
controlled

a different set
of muscles,

again, something
that still

has held true to this day.

Moving across to another
part of the world,

there was a renaissance
in about 1,000 AD of

Muslim science
and medicine that

spanned not only Iberia,

Southern Europe,
but we now call

Spain and Portugal,

all the way to
the Middle East.

And this Muslim
renaissance gave us

many advances in science
and in medicine.

And it particularly
focused on the question,

how can we understand and

treat mental
health disorders?

And one of the great
Muslim doctors and

scholars was known
as Al-Zahrawi,

and he lived in Islamic

Iberia and he described

many surgical
treatments for

neurological disorders
and brain trauma.

And he wrote a 30-volume
encyclopedia of

medicine called the
Kitab al-Tasrif.

The surgery chapter of

that volume was
translated into

Latin and for the
next 500 years

became the standard text.

Not that anyone today
would really want

to participate in any
of these surgeries,

but at the time,
from 1000-1500 AD,

they were state
of the art in

neurological surgery. At
around the same time,

in Persia, Ibn-Sina,

also known as Avicenna
in other rings,

he's often viewed as

the father of
modern medicine,

and his textbook, the
Canon of Medicine,

was used for
hundreds of years.

He described numerous
psychiatric disorders,

including mania,
hallucinations, dementia,

melancholia, or what we
now call depression,

and even described

a constellation
of symptoms

in people that he
called Junin Mufrit,

which maps very closely to

what we view as
schizophrenia.

So he really
developed a lot of

the basic understanding
and classifications of

the different mental
health disorders.

He also identified
and named

the cerebellar vermis

and the caudate nucleus.

And lastly, he
posited the brain as

the place where reason

interacts with sensation.

And that was
really critical

that it wasn't
just the thinking;

it was the interaction
between thinking,

and reason, and sensation.

And we very much
believe today that,

in fact, that's where much

of that intersection
takes place.

We now go back to Europe
next to the 1600s,

where Rene Descartes

asked the philosophal
question,

is the mind distinct
from the brain?

Now, Descartes was a firm
believer in dualism,

the principle
that the mind and

body exist as
separate entities,

each with a different
characteristics

and governed by
its own laws.

He also believed that
the pineal gland

was the link between
the mind and the body.

The pineal gland
lies in the chest.

Well, clearly, these
two approaches,

these two ideas
haven't held up well.

On the other hand,

he did develop the idea
of the reflex arc,

an automatic pathway from

a sensory stimulus
to a motor response,

and he diagrammed it here

in a sketch which pretty

much captures how we see

reflex arcs these days

coming in through the eye,

going to the brain,
and going out

through the muscles
in order to point.

By the mid 1800s,

there were a
number of people,

Bell, Flourens,
Harlow, Broca,

Wernicke, who all asked,

can localized
brain lesions

tell us about
the functional

organization of the brain?

We'll go through each of

these five men in order.

Charles Bell in
Scotland, again,

asked this question about

localized brain lesions

and what it tells

us about functional
organization.

He discovered
through dissection

and vivisection that

the spine transmit
motor impulses

and receives
sensory input.

He was a talented artist,

and you can see one of

his engravings in the
upper left corner,

and he published a
very influential

engravings of the brain.

He also described a
facial paralysis,

which is caused by

a damage to a
nerve in the face,

and is today known as
Bell's palsy after him.

In France, Jean
Pierre Flourens

showed that localized
brain lesions in

rabbits and pigeons
produced specific deficits

in motor control,
sensation, and behavior.

And he made three
important linkages.

He linked the cerebrum
to cognition,

the cerebellum
to movement,

and the medulla to
vital bodily functions.

And all of these are

basically the substance of

what we believe today.

On the other hand,

he didn't get
everything right.

He was a fervent
creationist,

and he argued against
Darwin's theory

of evolution by
natural selection.

Over here in the
United States,

John Harlow had a patient
named Phineas Gage,

who was working
on the railroad

when his frontal lobe was

pierced by an iron rod

that you can see here
from an autopsy,

literally went
through his cheek,

through his eye,

into his frontal
lobe, and surprising

everyone, Gage survived.

He still could
talk, he could

still function
to some degree.

But he lost what we
think of today as

executive control
over his behaviors.

He became impulsive and

easily distracted
and angry.

And so it was
from this that

Phineas Gage
suggested that

this part of the brain,

the front part
of the brain

of Phineas Gage was

critical for
these kinds of

executive controls
over our behavior.

Pierre Broca in
France studied

12 patients who lost

the ability to speak but

were still able
to comprehend.

And when these
patients died

and he autopsied them,

he showed that they
all had damage

in the left frontal lobe,

an area of the
brain now known as

Broca's area and believed

and known to be
key for speech.

Over in Germany, Carl
Wernicke was looking at

some very different
patients that

were essentially the
inverse or the opposite.

He studied patients who

lost the ability
to comprehend,

but they were still
able to speak.

Again, on later autopsies,

he showed that these
people had damage

in the superior
temporal gyrus,

an area now known
as Wernicke's area,

and critical for
comprehension.

And you can see
in the diagram

there, a modern diagram,

the difference
between Broca's area

and Wernicke's area,

suggesting that
comprehension and production

of language are subserved

by different
brain regions.

Moving ahead to
the late 1800s

back in the US,

William James asked, how
is memory organized?

He taught the
first course in

psychology ever
given in America,

and he was especially
interested

in how we learn new habits

and acquire new memories.

And to explain the
development of

memories and
how one memory

can trigger
another memory,

he described a
network model

where he suggested
that, at one event,

a dinner party, you might

remember the taste
of the food,

the sight of a
particular lady,

the smell of her perfume,

topics, and so forth.

And this dinner
party shares

some overlapping features
with another event,

which was going dancing,

where he saw
the same lady,

smelled the same perfume,

although this time in

a dance hall with

many other things
happening.

And so James suggested

two things that are
really important here,

which are still part of

our understanding of how
memory is organized,

that memories
are built up of

associations
among elemental

components that come

together to form
the whole memory,

and the ways in
which we relate

one complex memory to

another comes
from pathways

from associations
that go from

the common elements of

one event to
another event.

At around the same
time, in Spain,

Santiago Ramon
y Cajal asked,

what is the structure
of individual neurons?

And here we begin
to get down

into the molecular
mechanisms,

the cellular mechanisms,

in this case,
of the brain.

He utilized a cell
staining method

from Camilio Golgi.

And from his work, from

his analysis of these
cell stainings,

he developed what he

called the
neuron doctrine,

and he argued that
the functional unit

of the brain
is the neuron.

And this was later
supported by

electrical
stimulation studies

of Luigi Galvani,

who stimulated with
electrical current

and showed that
you could activate

muscles and
other movement.

In 1906, Cajal and

Golgi shared the
Nobel Prize.

And here, to see what an

exquisite artist and
scientist he was,

you can see here the

rodent hippocampus
from 1911,

and it's just a
phenomenal level

of detail that he

was basically able to
both see and to share.

Charles Sherrington,
by the early 1900s,

asked, what is
the function

of neurons and synapses?

He published an
influential book called

The Integrative Action
of the Nervous System.

He coined the
term synapse,

which we use today
for the point of

contact between
two neurons,

and he studied
the behavior

of neurons that
were either

activated or inhibited
at the synapse and

he argued that
it's the balance

between activation
and inhibition,

which is key to
muscle movement.

And for this
accomplishment,

he won the 1932
Nobel Prize.

Moving across
back to European,

Ivan Pavlov in
Russia was asking,

how and where are
learned reflexes formed,

these sorts of
reflexes that

Descartes had talked

about many years
beforehand?

Now, this wasn't his
initial interest.

He initially was
interested in the

digestive glands of dogs.

But inadvertently,
he discovered how

reflexes, such
as salivation,

can be conditioned
or trained as

a learned response to

a previously neutral
cue, such as a bell.

And in exquisite
experiments

over the coming years,

he was able to
characterize

all the various parameters

by which learning
and extinction,

the unlearning
can take place.

And for this in 1904,

he was awarded
the Nobel Prize.

We come now to the last of

the historical
landmarks that

I wanted to
share with you.

We're up now into the
1940s and the 1950s,

and Alan Hodgkin and
Andrew Huxley asked,

how do neurons use

electrical signals
to communicate?

They developed what we

call the
Hodgkin-Huxley model,

which describes how the
firing in a neuron is

initiated and propagated
to the next neuron.

And from this,

they develop
biophysical models

of the electrical
characteristics of

neurons shown in the graph

there in the lower left.

And for this, they won
the 1963 Nobel Prize.

So over the last
15 minutes,

I've taken you
on a tour of

about 2000 years from
400 BC in Greece,

through the Roman Empire,

to the Muslim Middle
East and Iberia, France,

Europe, the US,
Spain, England,

Russia, and back
to the USA.

And we've seen
the development

of all of these various
questions that were

being answered or
addressed with

whatever technology was

available during the day.

So I said at

the beginning that we

can think about
the history

of neuroscience as being

three different
approaches:

approaches of philosophy,

of functional anatomy,

and cellular mechanisms.

Today, there's not
really much philosophy,

although there are
people who study

the philosophy of mind,

but the focus
of neuroscience

is on three
other areas now.

There is the
functional anatomy,

still, which is a
really important area.

There's cellular
mechanisms,

which we began to see
in some of the history.

But more recently,

there's been an
understanding of

molecular mechanisms,

what happens inside
the cells from

the molecules
that are moving

around inside and
between cells.

You'll see more of
this in the weeks to

come and the months to
come in this course.

Functional anatomy is now

a critical part of
behavioral neuroscience,

cognitive neuroscience,
and neuropsychology,

all of which will
be presented

in the weeks to come.

Cellular mechanisms
are critical part

of the quest for
neurophysiology,

for understanding
neuropharmacology,

and neuropsychology.
And some

of that you'll be

seeing in the next
few lectures.

Molecular mechanisms
have been

the most recent addition

to what we try to
understand about the brain.

It has drawn on the fields

of molecular
biology, genetics,

and protein chemistry

to really get us down to

the nuts and bolts of

how the brain works
at a molecular level,

which helps us
understand at

the cellular level
and which, in turn,

leads us to understand

the functional
organization of the brain.

Now, all of these

are basic science
endeavors,

and that's the main
focus of this course.

But all of this has

an impact on neurology
and psychiatry,

the understanding
of brain disorders

and mental health
disorders.

And as we understand
functional anatomy,

cellular mechanisms,

and molecular mechanisms
of the brain,

they help us
understand some of

the neurological and
psychiatric syndromes

that are presented
in medicine.

And so with this

as an overview of
the history of

neuroscience and how this

relates to the structure

of the current field
of neuroscience,

you're now ready to begin

what I hope is going to be

a very exciting course in

the semester
ahead that will

introduce you to the
field of neuroscience.