1. What is a Brain?
Introduction to neuronal circuits, neurons, synapses, and non-invasive imaging

2. Organization of the Brain
Hemispheres
MRI imaging
PET imaging
Regions
2-deoxyglucose
labelling
Connections
Multi-cell
recordings
Neurons
Single-cell
recordings
Synapses
Electrical and chemical events

3. The Central Nervous System:
Brain
Spinal cord
Front Back
The Central Nervous System:
Slide 2: The brain and spinal cord
The central nervous system is composed of both the brain and the spinal cord. Describe the brain as a functional unit; it is made up of billions of nerve cells (neurons) that communicate with each other using electrical and chemical signals.

4. Spatial abilities, Face recognition, Visual imagery,
A split-brain patient fixates on the dot in the middle of a screen. Then a picture of a spoon is flashed to the right of the dot.
Spatial abilities, Face recognition, Visual imagery,
Music
Language,
Math, Logic
The visual information about the spoon crosses in the optic chiasm and ends up in the LEFT HEMISPHERE. The person correctly identifies the spoon verbally.

5. Spatial abilities, Face recognition, Visual imagery,
Now the picture of a spoon is flashed to the left of the dot.
Spatial abilities, Face recognition, Visual imagery,
Music
Language,
Math, Logic
Now the visual information travels to the RIGHT HEMISPHERE. Now if the subject is asked to identify the picture, he reports seeing nothing.
But, when this same subject is asked to pick out an object using only the LEFT hand, he correctly picks out the spoon. This is because touch information from the left hand crosses over to the right hemisphere - the side that "saw" the spoon.
However, if he is again asked to identify the object verablly, even when it is in his hand, he cannot do so because the right hemisphere cannot "talk." So, the right hemisphere is not stupid, it just has little ability for language - it is "non-verbal."

6. Function is often localized to specific brain regions
Front
Back
Slide 2: Brain regions and neuronal pathways
Certain parts of the brain govern specific functions. Point to sensory, motor, association and visual cortex to highlight specific functions. Point to the cerebellum for coordination and to the hippocampus for memory. Indicate that nerve cells or neurons travel from one area to another via pathways to send and integrate information. Show, for example, the reward pathway. Start at the ventral tegmental area (VTA) (in magenta), follow the neuron to the nucleus accumbens, and then on to prefrontal cortex. Explain that this pathway gets activated when a person receives positive reinforcement for certain behaviors ("reward"). Indicate that you will explain how this happens when a person takes an addictive drug.
acetylcholine
(nicotine)
and
dopamine

7. A typical pathway: sensation of pain and the reaction to pain
Slide 4: Pathway for sensation of pain and reaction to pain
This is a long pathway, in which neurons make connections in both the brain and the spinal cord. Explain what happens when one slams a door on one's finger. First, nerve endings in the finger sense the injury to the finger (sensory neurons) and they send impulses along axons to the spinal cord (magenta pathway). Point to each part of the pathway as you explain the flow of information. The incoming axons form a synapse with neurons that project up to the brain. The neurons that travel up the spinal cord then form synapses with neurons in the thalamus, which is a part of the midbrain (magenta circle). The thalamus organizes this information and sends it to the sensory cortex (blue), which interprets the information as pain and directs the nearby motor cortex (orange) to send information back to the thalamus (green pathway). Again, the thalamus organizes this incoming information and sends signals down the spinal cord, which direct motor neurons to the finger and other parts of the body to react to the pain (e.g., shaking the finger or screaming "ouch!").

8. Spinal reflexes, such as the knee-jerk, involve just two neurons.
sensory neuron
motor neuron
the sensory neuron acts like a strain gauge wrapped around a special muscle fiber.

9. Electricity is also a language of the nervous system
Slide 10: Injection of cocaine into the nucleus accumbens
Demonstrate how scientists located the structures important for the addictive nature of drugs. Show that a rat will self-administer cocaine directly into the nucleus accumbens (or the VTA) to activate the pathway. Point to an area close to the nucleus accumbens or VTA and state that if the injection is placed in this other area, the rat will not press the lever to receive the drug. Indicate that scientists know a lot more than where the drug acts to produce rewarding effects - they also know how the drugs work. Show examples with cocaine, heroin and marijuana.
Electricity is also a language of the nervous system

10. 2-deoxyglucose can label thousands or millions of active cells at once
(radiolabelled)
glucose
glucose phosphates
metabolic products,
ATP
cell
2-deoxyglucose phosphates
No metabolic products;
label remains in cell
activity

11. Positron emission tomography (PET)
Positron emission tomography (PET). The probe is [18F]fluoro-2-deoxyglucose. The 18F nucleus decays, eventually yielding a positron which annihilates with an electron to produce a pair of g rays (photons). These travel in opposite directions. The two coincident photons intersect an array of detectors. The point of origin is on the line between the two detectors; and “tomography” is the set of algorithms that compute the point of origin from many independent events.

13. A functional magnetic resonance imaging (fMRI) image
A functional magnetic resonance imaging (fMRI) image. This is the rear view of a human brain activation associated with performance of a task that utilizes motor, visual and planning cognitive processes. The subject was moving a joystick to follow a target around a video display.

14. Nuclear Magnetic Resonance
Nuclei of interest Proton 1H H2O, fat, NAA
Carbon 13C
Sodium 23Na
Phosphorus 31P ATP,ADP,Pi
Xenon 129Xe
These nuclei possess spin angular momentum (mh/2p)
& thus a magnetic moment (m)
m= I, I-1, …-I 2I+1 values of m
m=gIh/2p
g gyromagnetic ratio

17. Slide 3: Neuronal Structure
Remind the student that pathways are made up of neurons. Describe the anatomy of a neuron (soma, dendrites and axon are marked with text). State that this neuron is real - as viewed through a microscope. Explain the normal direction of impulse flow. Dendrites and soma receive chemical information from neighboring neuronal axons. The chemical information is converted to electrical currents which travel toward and converge on the soma. A major impulse is produced (the action potential) and travels down the axon toward the terminal. Point to the terminal.

18. Action Potentials and Single Channels

19. What are the consequences of the charge imbalance?
The “Na+ pump” splits ATP to make a Na+ and K+ concentration gradient
What are the consequences of the charge imbalance?
A transporter protein moves a few ions for each conformational change

20. Na pump = current source
very large = = E
very large

21. V
pump
channel

22. V
pump
channel
ATP

23. V + pump channel DV = IR ATP -
The Na pump drives the membrane potential
more negative
(the cell “hyperpolarizes”)
DV = IR
ATP -

24. Major Roles for Ion Channels
actually, DE
electric field
open
closed
electrical transmission in
axons:
Monday:
[neurotransmitter]
open
closed
chemical transmission at
synapses:

25. Little Alberts Fig 12-30

26. action potential
noun Date: : a momentary change in electrical potential (as between the inside of a nerve cell and the extracellular medium) that occurs when a cell or tissue has been activated by a stimulus.

27. The frequency of impulses represents signaling among cells in the nervous system.
-from sense organs to the brain
-within the brain
-from the brain to muscles
-even in a muscle or in the heart
-even in the pancreas

28. The synapse is a point of information processing
Slide 6: Impulse flow
Explain the normal direction of the flow of information (electrical and chemical). An electrical impulse (the action potential) travels down the axon toward the terminal. Point to the terminal. The terminal makes a connection with the dendrite of neighboring neuron, where it passes on chemical information. The area of connection is called the synapse. While the synapse between a terminal and a dendrite (shown here) is quite typical, other types of synapses exist as well--for example a synapse can occur between a terminal and a soma or axon.
An adult human brain contains ~ 1011 neurons , and each of these might receive 103 synapses apiece, for a total of 1014 synapses. Most of these synapses form during the first 2 yr of life.
Thus 1014 synapses/108 s = 106 synapses/s form in a fetus and infant!

29. Synapses

30. Cerebral cortex
Axons
Dendrites
Synapses
Synaptic vesicles (volleyballs), mitochondria (watermelons)
1. Movements do not occur in 1 ms; vesicles are already “docked”.
2. Neurotransmitter diffuses across the synaptic cleft in a few ms
3. “Slight” errors cause mental illness? Unproven!
(But single-codon mutations do cause some neuroscience diseases)

31. cytosol cell body presynaptic terminal kinesin 50 nm Neurotransmitter
and
ATP
~ 20 distinct proteins
vesicle transport;
pumping protons;
pumping neurotransmitter;
docking;
fusion;
recycling.
cytosol

32. ATP-driven proton pump cytosolH+
ATP-driven proton pump
cytosol
proton-coupled
neurotransmitter pump
Neurotransmitter
and
ATP
(1,000 to 10,000 molecules
of each)
cytosol
cytosol
~ isotonic!

33. Electricity, then chemistry triggers synaptic vesicle fusion
docked vesicle
neurotransmitter
nerve impulse
voltage-gated
Ca2+ channel

34. Electricity, then chemistry triggers synaptic vesicle fusion
docked vesicle
neurotransmitter
Ca2+
nerve impulse
voltage-gated
Ca2+ channel

35. Electricity, then chemistry triggers synaptic vesicle fusion
fused vesicle
Ca2+
neurotransmitter

36. The heavy chain of botulinum toxin is an enzyme
that cleaves synaptic vesicle fusion proteins

37. Receptors and Ion Channels as
What is a Receptor?
Receptors and Ion Channels as
Examples of Proteins

38. Most drug receptors are proteins.
a molecule on the cell surface or in the cell interior that has an affinity for a specific molecule (the ligand).
Latin,
“to tie”
Most drug receptors are proteins.
Greek, “first”

39. Chemistry is a language of the nervous system, for instance at synapses
Slide 7: The synapse and synaptic neurotransmission
Describe the synapse and the process of chemical neurotransmission. As an electrical impulse arrives at the terminal, it triggers vesicles containing a neurotransmitter, such as dopamine (in blue), to move toward the terminal membrane . The vesicles fuse with the terminal membrane to release their contents (in this case, dopamine). Once inside the synaptic cleft (the space between the 2 neurons) the dopamine can bind to specific proteins called dopamine receptors (in pink) on the membrane of a neighboring neuron. This is illustrated in more detail on the next slide.

40. Na+-coupled
cell membrane
serotonin
transporter
dopamine
cytosol
synaptic
cleft
cytosol
postsynaptic
G protein-coupled
serotonin
receptor
dopamine

41. a a b b g g Drugs act on the G protein pathway. How fast?
100 ms to 10 s
How far?
Probably less 1 mm
Neurotransmitter or hormone
binds to receptor
activates
G protein
Effector:
enzyme or channel
outside a b g a b g
inside
GTP
GDP + Pi
Effector