Transcript 1) Propagated electrical signals - UW Canvas

Learning at the synapse
Bertil Hille, PhD
Physiology and Biophysics
University of Washington School of Medicine
Seattle Washington, USA
?
(i) challenge learning cycle
(ii) signaling mechanisms
(iii) strengthening synapses
How do I learn Project © Bertil Hille 2013
Greek WORD:
Metacognition
"knowing about knowing"
(Anglo-Saxon)
How do we learn: The challenge cycle.
(John Bransford)
?
challenge
question
initial
thoughts
report
revise
discuss
resources,
more
information
Philosophers (Socrates, Plato, Aristotle -- 5-4th C. BC)
?
challenge
question
report
hypothesis
inductive
reasoning
resources
Scientists
?
challenge
question
publish
(or perish)
da capo
da capo
da capo
hypothesis
da capo
da capo
da capo
revise
experimental
tests
"Scientific Thinking in
Young Children"
(Alison Gopnik)
The carpet
Learning child
?
challenge
question
report
da capo
da capo
da capo
first guess
da capo
da capo
da capo
revise
trials
Science studies Nature
What is nature.
Nature is what is.
But is nature natural.
No not as natural as that.
(Gertrude Stein—
The Geographical History of America:
Or the Relation of Human Nature to the Human Mind)
Nature is what we see
......
Nature is what we know—
Yet have no art to say—
So impotent Our Wisdom is
To her Simplicity.
(Emily Dickinson)
Many
levels
of
science
and
nature
Magnetic
resonance
image (MRI)
of a human
head
(UW Hospital)
Hearing words
WORDS in PET! Seeing words
Speaking words
Q: How do parts of the brain communicate?
Thinking about words
max
min
(M. Raichle, 1998)
PET: positron emission tomography
Visual cortex
like a computer chip
I
II
III
IV
A
B
C
V
D
VI
Visual cortex
I
II
Nervous System
Zillions of neurons
III
Wires itself
IV
Refines itself
Reconfigures after injury
Learning modifies it
V
"Plasticity"
"Critical period" (e.g. spinal
VI
injury, language)
Three modes of nervous signaling
1) Propagated electrical signals
electrical to electrical to electrical
encode
propagated
spike
3) “Hormonal" neuro-modulation
Fast point-to-point wiring
chemical
to
intracellular
Like a calculator
"presynaptic"
2) Fast chemical transmission
at chemical synapses
electrical to chemical to electrical
presynaptic
biochemical
cascades
many "postsynaptic cells"
postsynaptic
cell
membrane
Potential EM
Neurons encode intensity as spike frequency
0
20 mV
membrane
potential EM
weak excitatory stimulus
0
stronger excitatory stimulus
0
time (seconds)
1
(Conner & Stevens, 1971)
Axon spikes: a propagating electrical wave
measure
cell voltage
Recording
setup
living axon
spikes recorded
at points a and b
in the axon
membrane
voltage
EM (mV)
0
0.5
1.0
1.5
Time (milliseconds)
The spike is the
long- distance,
reliable,stereotyped,
rapid, specific,
electrical signal of
axons & muscles
How does a nerve make its electrical spike signal?
Step1:
A few Na+
ions enter
cell
Na+
so cell inside
goes positive
1
E
Step 2:
A few K+ ions
leave cell
Step 1:
Na+
A few Na+
ions enter cell
so cell inside
goes positive.
1
2
E
Step 2:
A few K+ ions
leave cell
time
K+
so cell inside
returns to
rest.
2
Moving
Ions
Make
Electrical
Signals in
Nerve
Hodgkin &
Huxley
(1952)
Hypothesis:
Moving
ions make
electrical
signals
in nerve
time
K+
so cell inside
returns to rest -negative
Gated ion channels do it!
(Hodgkin &
Huxley 1952)
Outside
cell
Inside
cell
Ions pass through a gated
aqueous pore.
The voltage sensor regulates
the gate.
nm
Outside
cell
Inside
cell
Ions pass through a gated
aqueous pore.
The voltage sensor regulates
the gate.
nm
Three modes of nervous signaling
1) Propagated action potentials
electrical to electrical to electrical
encode
propagated
spike
3) “Hormonal" neuromodulation
Fast point-to-point wiring
chemical
to number
intracellular
And "The
is …"
"presynaptic"
2) Fast chemical
synaptic transmission
electrical to chemical to electrical
presynaptic
neuron
biochemical
cascades
many "postsynaptic cells"
postsynaptic
cell
Visual cortex
Computer chip
I
II
III
IV
A
B
C
V
D
VI
Synaptic terminals speaking to a spinal motoneuron
Neurons may receive 10,000 synaptic contacts, some excitatory and some inhibitory,
on its cell body and dendrites. (Haggar & Barr, 1950)
Each synapse is a voter: casting a yea or nae vote
A fast
chemical
synapse
Terminal of
presynaptic
neuron
synaptic vesicle filled
with neuro-transmitter
Chemical synapse
voltage-gated
Ca2+ channel
synaptic
vesicle
release
Let’s focus on
active zone and
release
synaptic
mechanism
ligand-gated
ion channel
cleft
Postsynaptic neuron
SNARE
helical winch
& Ca2+ trigger
Ca2+
Vesicle
membrane
SNAP-25 (t-SNARE)
Syntaxin (t-SNARE)
Neurotoxin
cleavage
spots
marked
BoTox &
TeNT
VAMP (v-SNARE)
Cell membrane
C
Ca2+
(Sutton et al. 1998)
A family of neurotransmitter receptors
Outside: in the
synaptic cleft
Inside: In the
muscle fiber
0
10
20
scale (nm)
The receptor is also an ion channel: an electrical vote
Nervous signaling
1) Propagated action potentials
electrical to electrical to electrical
encode
propagated
spike
Fast point-to-point wiring
like a calculator
2) Fast chemical
synaptic transmission
electrical to chemical to electrical
presynaptic
neuron
How does this learn!
postsynaptic
cell
Learning at the synapse
?
(i) challenge learning cycle
(ii) signaling mechanisms
(iii) strengthening synapses
© Bertil Hille 2013
Associative learning needs coincident convergence
Associative learning
Pavlov's dog (1901)
FIRST
Conditioned
stimulus
(bell)
SOON Unconditioned
AFTER stimulus
Hebb's synapse (1949)
(food)
Associative learning
Proposal: Learning is strengthening and weakening of synaptic connections
"Neurons that fire together
wire together"
(Carla Schatz)
Synapses can be strengthened by coincident inputs
Synapses strengthen if
they successfully
participate in firing a cell.
(Donald Hebb, 1949)
A test in a hippocampal
neuron (1973)
Long term potentiation
(LTP)
*
response
at test
synapse
LTP
LTP can increase available post-synaptic receptors
Post syn. cell membrane
L
T
P
0
10
Additional receptors insert into postsynaptic membrane = stronger synapse
Spines are landing pads for synapses
30 um
Neurons in cerebral cortex (Bear and Sabatini)
10 um
Crowding of synaptic terminals on a spine
Pre10
Pre9
Pre8
Pre7
Pre1
Postsynaptic
Pre5
Pre6
Pre4
Pre2
Pre3
1 mm
(Peters, Palay, Webster, 1991)
Another way to learn: grow new synapses
10 um
Spines are landing pads for
synapses. New spines grow to
strong sources of neurotransmitter.
(Sabatini , 2012)
Associative learning needs coincident convergence
Associative learning
Pavlov's dog (1901)
FIRST
Conditioned
stimulus
(bell)
SOON Unconditioned
AFTER stimulus
Hebb's synapse (1949)
(food)
"Neurons that fire
together wire
together"
(Carla Schatz)
Associative learning
Proposal: Learning is strengthening and weakening of synaptic connections
Scientists, philosophers, students, babies
?
learning cycle
signaling
mechanisms
challenge
strengthening
questionsynapses
publish
(or perish)
da capo
da capo
da capo
hypothesis
da capo
da capo
da capo
revise
experimental
tests
Challenges for knowing about knowing!
(i) challenge learning cycle
(ii) signaling mechanisms
(iii) strengthening synapses
How can you enhance plasticity?
How do you look up your old telephone number?
Where are hypotheses kept?
How are language and syntax acquired?
How are they generated?
Can neuroscience aid pedagogy?
Thank you!