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Biosciences in the 21st century Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger

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Page 1: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Biosciences in the 21st century

Lecture 1: Neurons, Synapses, and Signaling

Dr. Michael Burger

Page 2: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Outline:

1. Why neuroscience?

2. The neuron

3. Action potentials

4. Synapses

5. Organization of the nervous system

6. Clinical approaches of today and tomorrow

Page 3: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Figure-ground illusions are well known for visual stimuli

Page 4: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

The Müller-Lyer Illusion

Page 7: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

What did he say?

Page 8: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

What did he say?

http://www.media.uio.no/personer/arntm/english.html

Page 9: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Now close your eyes!

Page 10: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?
Page 11: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Hearing gaps

Page 12: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

But they occur in the auditory system too!

Page 13: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Alzheimer’s Disease

more than 5 million people in the United States living with Alzheimer’s.

The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion annually.

Parkinson’s disease:3% of population over 65: 1.5 million patients

Hearing Impairment:Approximately 28 million Americans have a hearing impairment

Approximately 314 in 1,000 people over age 65 have hearing loss and 40 to 50 percent of people 75 and older have a hearing loss.

Paralysis:

2.4 million Americans are paralyzed

Depression:

over 20 million Americans suffer from depression

Page 14: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

The BIG THREE topics for today:

1. What is the basis of electrical signaling in neurons?

1I. How do neurons “talk” to each other?

I1I. How do neurons encode information?

Page 15: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

synapse

The neuron is the “unit of processing” for the nervous system

(glia)

Page 16: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

a

The cell membrane is a phospholipid bilayer

plasma membranenucleus

Page 17: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

Inside: Cytoplasmic

Outside: Extracellular

_

+ + + + +

_ _ _ _

Positive

Negative

Cell membranes store Voltage

Vmembrane= -60 mV_ _ _ _ _

**The inside of the cell is usually more negative than the outside by about -60 mV

Page 18: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

Cytoplasmic

Extracellular

Na+

Na+

K+

K+

_

+ + + + +

_ _ _ _

This “resting” voltage depends on ion distribution,and ions in general cannot cross the membrane

An- (organic anions;

ie proteins)

Cl-Ca++

_ _ _ _ _

Page 19: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

The cell membrane contains proteins, some of which are channels for charged particles

a

a

a

a

Page 20: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

Two (of many) membrane protein types:

Ligand gated(chemically gated) Voltage gated

+

_

+

_

Page 21: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+ + + + Na+ channel

a

K+ channel

How does an electrical signal occur in a neuron?

+ ++ +

_

+ + + + +

_ _ _ _

Na+ and K+ channels have slightly different gating properties (Na+ is fast, K+ is slower)

Page 22: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+ + + + Na+ channel

a

K+ channel

How does an electrical signal occur in a neuron?

+ ++ +

_

+ + + + +

_ _ _ _

FIRST, WE GIVE THE Na+ CHANNEL A STIMULUS

Page 23: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+ + ++

a

_

+ + + + +

_ _ _ _

Page 24: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+

+

++

a

_

+ + + + +

_ _ _ _

Page 25: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+

+

++ Voltage

a

_

+ + + + +

_ _ _ _

Page 26: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+

+ ++Voltage

a

+++

+ Voltage gatedK+ channel

_

+ + + + +

_ _ _ _

Page 27: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a a

Cytoplasmic

Extracellular

Na+

K+

a

+

a

+

_

+ + + +

_ _ _ _

VoltageVoltage

a

Membrane Voltage-60mV

Page 28: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

One more detail....

The voltage change travels...

Page 29: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

Na+

K+

a a

a

+

++ +

Voltage

a

_

+ + + + +

_ _ _ _

a a

The basis of propagation....

Page 30: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

Membrane Voltage

1

2

3

1. Na+ channels open/Na flows into the cell2. Na+ channels close while K+ channels are opening3. K+ flow out of the cell dominates

a

a

a

a

direction of travel

Action Potential Summary:

Page 31: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

NEXT:

How do neurons “talk” to each other?

Page 32: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

a

a

Ca++

a

Synaptic Transmission

Step 1: Depolarization of the axon terminalStep 2: Voltage dependent Ca++ entry

12

axon dendrite

axonterminal

vesicle+transmitter

postsynaptic receptor

Page 33: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

a

a

Ca++

a

Step 3: Ca++ dependent vesicle fusionStep 4: transmitter release

3

4

Synaptic Transmission

Page 34: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

a

a

Ca++

a

Na+

+

Step 5: Activation of ligand gated channelStep 6: Na+ flux/dendrite depolarization

5

6+

+

Synaptic Transmission

Page 35: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

a

a

Ca++

a

Na+

+

Step 5: Activation of ligand gated channelStep 6: Na+ flux/dendrite depolarizationStep 7: Action Potential is regenerated postsynaptically

5

6+

+

Synaptic Transmission

a

7

a

a

Page 36: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Very large auditory synapse

Page 37: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Stain in red marks postsynaptic receptors

Page 38: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

Evaluating Neural responses

+

Presynaptic neuron

a

a

Electrode

a

a

Amplifier

ActionPotential

Postsynaptic neuron

Page 39: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

How do neurons encode information?

there are two simple ways.....

AND Finally,....

Page 40: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

no sound

evoked

100 ms tone

a

with action potential TIMING....

Page 41: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

aaa

10

20

40

30

50

60

70

Intensity(dB SPL)

100 ms tone100 ms tone

...and Neurons signal by changing their firing rateLo

uder

Page 42: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

a

a

a

Stimulus Intensity

Spik

e R

ate

Spike Rate increases with Intensity

Page 43: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

What we learned today:

1. Neurons and glia: characteristics and function

2. Ionic basis of electrical signaling

3. Basics of chemical synaptic signaling

4. How neural activity is recorded

5. How neural activity relates to information processing

Page 44: Lecture 1: Neurons, Synapses, and Signalinginbios21/PDF/Fall2011/Burger_09052012.pdf · Lecture 1: Neurons, Synapses, and Signaling Dr. Michael Burger. Outline: 1. Why neuroscience?

Next time....

Brain organization

New technologyfor therapy