Transcript Methods for Studying Brain/Behavior Relationships

Experimental Approaches to
Studying Brain/Behavior
Relationships
Chapter 5 Supplement
Copyright 2001 Michael A. Bozarth
Overview of Various Experimental Methods
Used to Study Brain/Behavior Relationships
manipulation
measurement
other
stimulation
electrical
chemical
local anesthetic
inhibition
reversible
spreading
depression
electrical
irreversible
lesion
chemical
single-unit
recording
neuroimaging
autoradiography PET fMRI
2-deoxy-D-glucose
knife cut ablation
chemical
multiple-unit
recording
cfos (The New 2DG)
vacuum
substance specific
evoked potential
electrolytic & cell-body
radiofrequency specific
neurotransmitter
specific
regional assay
EEG
postmortem analysis
micropunch assay
real-time in vivo analysis
in vivo microdialysis
in vivo voltametry
Copyright 2001 Michael A. Bozarth
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Copyright 2001 Michael A. Bozarth
Experimental Manipulations Used to
Study Brain/Behavioral Relationships
• Manipulation
– Stimulation: involves activating select brain
area and determining if the behavior occurs
when it would normally be absent (e.g., eating
in food-satiated subjects)
– Inhibition: involves disrupting the neural
activity of select brain area and determining if
the behavior fails to occur when the eliciting
stimulus is present (e.g., eating in foodreturn to overview
deprived subjects)
Copyright 2001 Michael A. Bozarth
Stimulation of Brain Activity
• Electrical: involves stimulating neurons by
delivering brief pulses of electrical current
through surgically implanted
macroelectrodes
• Chemical: involves stimulating neurons by
microinjecting small quantities of
neurotransmitters or other substances
through surgically implanted cannula
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Copyright 2001 Michael A. Bozarth
Electrical Brain Stimulation
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Copyright 2001 Michael A. Bozarth
Inhibition of Brain Activity
• Reversible: involves temporarily disrupting
neural activity in discrete brain areas
• Irreversible: involves permanently
disrupting neural activity in discrete brain
areas
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Copyright 2001 Michael A. Bozarth
Experimental Measurements Used to
Study Brain/Behavioral Relationships
• Measurement
– Electrophysiological activity: studies changes
in electrical activity associated with behavior
– Neurochemical changes: studies changes in
neurochemical activity associated with behavior
– Neuroimaging: uses special markers (e.g.,
glucose uptake, neurotransmitter-specific
‘tags’) to determine changes in neural activity
associated with behavior
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Copyright 2001 Michael A. Bozarth
Electrophysiological Recording
• Single-unit recording: studies the electrical
activity of individual neurons
• Multiple-unit recording: studies the
composite electrical activity of groups of
neurons (e.g., fiber pathway)
• EEG recording: studies the low frequency,
composite electrical activity of unspecified
origin at select brain regions
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Copyright 2001 Michael A. Bozarth
Reversible Inhibition of Brain Activity
• Local anesthetic microinjection : lidocaine
can be used to disrupt neural activity by
blocking voltage-gated Na+ channels
• Spreading depression: KCl can be applied
to inactivate large cerebral regions
• Other techniques have been tried with limited
success, e.g., cryogenic probes slowing brain
activity by regional cooling
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Copyright 2001 Michael A. Bozarth
Irreversible Inhibition of Brain Activity
• Ablation
– chemical
– vacuum
• Knife cuts
• Lesions
– radio frequency
– electrolytic
– cell-body selective (i.e., excitatory amino acid
neurotoxins; e.g, kainic acid)
– neurotransmitter specific (e.g, catecholamines, 6-OHDA)
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Copyright 2001 Michael A. Bozarth
Neurochemical Analysis
• Postmortem analysis: determination of
various brain chemicals in sacrificed subject
after the behavior has been observed
• Real-time in vivo analysis: determination
of various brain chemicals during the
behavior under study
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Copyright 2001 Michael A. Bozarth
Neuroimaging Techniques
• Autoradiography: determines the
distribution of various radio-labeled
substances in brain slices (sacrificed subjects)
• Positron Emission Tomography (PET):
determines the distribution of radio-labeled
substance using computer tomography
• Functional Magnetic Resonance Imaging
(fMRI): determines brain activity from
oxygen utilization during MRI
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Copyright 2001 Michael A. Bozarth
Radio-Labeled Tags/Tracers
• Virtually any organic substance can be
labeled with a radioactive atom
• Commonly used isotopes are H3 and C14
• Radioactive particles (either beta or gamma
particles) darken x-ray film in proportion to
their specific activity (i.e., more H3
produces darker image)
• Special radiation detectors can also be used
with computer-aided reconstruction
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Copyright 2001 Michael A. Bozarth
Computer Tomography (CT)
• Computer-driven scanning x-ray that
permits two-dimensional reconstruction at
all levels through the brain
• Used to visualize pathological brain and
identify locus of damage or abnormality
• Relatively inexpensive procedure
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Copyright 2001 Michael A. Bozarth
Magnetic Resonance Imaging (MRI)
• Images formed by the interaction of radio
waves with hydrogen in a strong magnetic field
• Provides very detailed reconstruction based on
the variable hydrogen content of different
tissues
• More costly procedure than CT but has much
greater capabilities (e.g., not limited to
horizontal plane
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Copyright 2001 Michael A. Bozarth
Other Methods of Measuring
Neurotransmitter-Related Substances
• Two methods are widely employed for localizing
proteins related to brain function (e.g., enzymes)
– only detects proteins (and thus not neurotransmitters!)
– most valuable for determining long-term changes in
protein synthesis related to altered neural activity
– can be used for visualization and for quantification
• Immunocytochemistry: localizes proteins through
dye-labeled antibody
• In situ hybridization: localizes mRNA directing
protein synthesis through radio-labeled cRNA
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Copyright 2001 Michael A. Bozarth