Copyright 2001 Michael A. Bozarth 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 manipulationmeasurement stimulationinhibition electricalchemicalreversibleirreversible electricalchemicalneuroimaging single-unit recording local anestheticspreading depression lesionablation electrolytic & radiofrequency cell-body specific neurotransmitter specific multiple-unit recording evoked potential PETfMRIautoradiography EEG knife cut 2-deoxy-D-glucose cfos (The New 2DG) in vivo microdialysisin vivo voltametry substance specific real-time in vivo analysispostmortem analysis micropunch assayregional assay chemical vacuum other
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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 food- deprived subjects) return to overview
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 return to overview
Copyright 2001 Michael A. Bozarth Electrical Brain Stimulation return to overview
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 return to overview
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 return to overview
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 return to overview
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 return to overview
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) return to overview
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 return to overview
Copyright 2001 Michael A. Bozarth Neuroimaging Techniques Autoradiography: determines the distribution of various radio-labeled substances in brain slices (sacrificed subjects)radio-labeled Positron Emission Tomography (PET): determines the distribution of radio-labeled substance using computer tomographycomputer tomography Functional Magnetic Resonance Imaging (fMRI): determines brain activity from oxygen utilization during MRIMRI return to overview
Copyright 2001 Michael A. Bozarth Radio-Labeled Tags/Tracers Virtually any organic substance can be labeled with a radioactive atom Commonly used isotopes are H 3 and C 14 Radioactive particles (either beta or gamma particles) darken x-ray film in proportion to their specific activity (i.e., more H 3 produces darker image) Special radiation detectors can also be used with computer-aided reconstruction return to overview
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 return to overview
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 return to overview
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 return to overview