Transcript C! **D!**E!**F! - Amherst College

AMHERST COLLEGE
INTRODUCTION TO NEUROSCIENCE
WEDNESDAY, JANUARY 30, 2008
Chen, Sandi S.
Coombs, Angela A.
Guha, Pallabi
Gutierrez, Christina
Hopkins, Christina C.
Howard, Clare E.
Kativhu, Chido L.
Kim, Daniel W.
LaMontagne, Laurel
Mattison, Jamie E.
Montgomery, Tracy
Navarro, Yasmin
Rivera, Ashley M.
Salgado, Sanjay M.
Thein, Thuzar
Tsareva, Alina
Zhang, Wen
Zhu, Victor
Wednesday lab
Reading: Chapter 1 & 2
Friday: Chapter 7: 168-180;
193-199; 205-235
Chapter 15 (490-497)
Tuesday lab
HOW WE STUDY BRAIN & BEHAVIOR (CONT.)
Anderson, Nicolle
Cai, Sophia L
Cameron, Rachel
Dalton, Elizabeth D.
Dier, Kirsten N.
Gladstone, Alexandra
Glick, Michelle S.
Hartley, Iris R.
Holaday, Eric J.
Jeppson, Pamela
Jiang, Debbie C.
Kundu, Surya
Lim, Tiffany M.
Ludwig, Susannah W.
Moin, Emily E.
O'Loughlin, Kerry
Romanowicz, Jennifer
Waskom, Michael L
Neuroscience definition & history –
• Neuroscience: The
study of1behavior and the
Chapter
mind through the study of the nervous system.
• Mind and brain:
– “Today, some people still believe that there is a
‘mind-brain problem,’ that somehow the human mind
is distinct from the brain. However, as we shall
see…, modern neuroscience research supports
another conclusion: The mind has a physical basis,
which is the brain.”
– Combustion of gasoline is the physical basis of a
car’s movement, but the car’s movement is distinct
from the combustion of gasoline.
Chapter 1 questions
• Before it was understood that nerves signal using electricity,
what mode of signalling was attributed to nerves?
• What is the earliest experiment (as distinct from observation)
cited in Chapter 1?
• What are the arguments that experiments on animals such as
rats can be relevant to understanding human behavior, human
mental life, and human brain diseases?
What is the brain made of?
•
•
•
•
Cells: individual or syncytium?
Cell types
Extracellular space in brain tissue
Ventricles
How we study…
A. Nerve cell structure
B. Neurons in isolation
C. Connections between different parts of the
nervous system
D. Electrical activity
E. Chemical signalling between neurons
F. Relation between brain activity and behavior
A. Nerve cell structure: 1. Nissl and other
traditional stains
100 m
2. Golgi method
Dendrites
Silver or mercury salts, precipitate within neurons
Axon
-Camilo Golgi, 1870s
-used by Santiago Ramon y Cajal, 1880s-1920s Soma
(cell body)
The “Neuron Doctrine”
3. Fluorescence labelling
Neurons vs. glia
Fused neurons
(University of Florida)
(Institute of Biophysics, Beijing)
…with computer processing
4. Electron microscopy
Shorter wavelength = higher resolution
1 m
Cell membrane
Neurons: a composite picture
The neuron: your
typical cell, and
more!
Text Fig. 2.7
B. Studying living nerve cells in isolation
from their normal surroundings
• Gray vs. white matter – are axons a separate
type of cell?
• Cell and tissue culture
– Invented by Ross Harrison in 1909 to study this
question
C. Tracing connections between different
parts of the nervous system
Pathway tracing:
• Dye transport along axons, e.g. Fast Blue
• Lesion + degeneration-specific staining
• Radioactive tracers (3H-proline)
Inject into one eye,
observe in visual cortex
Text, Fig. 22.18
• Other chemical tracing: horseradish
peroxidase (anterograde or retrograde)
Horseradish peroxidase
HRP is a plant enzyme. It is transported down
nerve axons, and it creates colored product
when tissue exposed to hydrogen peroxide
(H2O2)
(H2O2
H2O + O, O + chromogen
color)
Inject HRP
into left eye
From: Kay Fite, UMass
D. Studying the electrical activity of neurons
“Electrophysiology:”
• Surface recording – evoked potentials, EEG
– Populations of neurons
– Can be done in humans
• Single neuron recording
• Patch clamp recording
Single neuron recording: intracellular
Glass micropipette:
- Tip diameter 0.5 um
- Filled with salt solution
- Records electrical
difference across the
cell membrane
Fig. 3.11
Single neuron recording: extracellular
Sharpened metal probe, tip diameter 1 – 5 um
Records electrical currents flowing outside neurons
Voltage
Time
E. Studying chemical signalling:
Pharmacology
• How can chemicals have effects in the body
at very low concentrations?
• Concepts:
–
–
–
–
Receptors
Specific binding
Multiple subtypes for a single neurotransmitter
Agonists, antagonists
Measuring chemicals and chemical signals
(1) Immunological methods
– Antibody to specific protein, e.g.
receptor
– Single brain section:
Immunohistochemistry
– Piece of brain tissue: Western
blotting – ‘gel’
(2) Receptor autoradiography
- Radioactively labelled
neurotransmitter (or chemical analog
of the transmitter molecule) binds to
receptor
C-fos immunohistochemistry
(3) In situ hybridization – radioactively labelled nucleic acid “probe”
detects specific messenger RNAs
F. Studying the relationship between
behavior and brain activity
• Observe brain correlates of behavior
(electrical activity, fMRI, 2-deoxyglucose)
• Change brain activity and see effect on
behavior
– Decrease activity: lesions, chemical block
– Increase activity: electrical or chemical stimulation
• Need for animal experiments:
– Electroencephalogram vs. single neuron recording
– Accidental vs. experimental lesions
Brain imaging
• CAT (CT) scan – computed tomography
• Magnetic Resonance imaging
– Spin of atomic nuclei perturbed by a pulse of
strong magnetic field; when the nuclei return
to normal spin they send a signal
– Regular MRI: Regions of different water
composition give a different signal
– Functional MRI: detects metabolic
differences (hemoglobin when
oxygenated vs. unoxygenated)
From: Scott Rauch ’80
(MGH)
Example 1: 2-deoxyglucose
• Radioactively labelled 2DG is taken up by
cells as glucose is, but isn’t metabolized.
– Highly active cells take up lots of 2DG
– After desired stimulation or behavioral
observation, look for labelled regions
Example 2: lesions
• Cut, freeze, heat (via high electrical frequency), toxic
chemical (as in our lab later this semester)
• Problems:
• Not always precisely specific to desired region
• Fibers of passage
Example 3: Brain injections of
neurochemicals
• Neuropeptide-Y (NPY) and Melanin Concentrating
Hormone (MCH) both increase food intake.
• NPY neurons project to MCH neurons.
– Hypothesis: MCH neurons mediate the downstream effects
or “commands” of NPY on feeding.