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METHODS OF STUDYING THE NERVOUS SYSTEM Outline 1. Methods of Visualizing the Living Human Brain a. Contrast X-rays b. Computerized Axial Tomography c. Magnetic Resonance Imaging d. Positron Emission Tomography e. Functional MRI 2. Scalp Electroencephalography 3. Invasive Physiological and Pharmacological Methods a. Stereotaxic Surgery b. Lesion Methods c. Electrical Stimulation d. Pharmacological Methods CT scan of a man struck by lightning – basal ganglia damage PET Scan of Normal (left) and Alzheimer's Disease (right) Brains Intracellular unit recording Extracellular Unit recording Routes of administration Intragastric (IG) Intraperitoneal (IP) Intravenous (IV) Subcutaneous (SC) Intramuscular (IM) Many drugs cannot pass the blood-brain barrier Microinjection 6-hydroxydopamine (6-OHDA) Measuring the Chemical Activity of the Brain: 2-deoxyglucose autoradiography radioactive 2-DG is injected animal performs the behavior of interest animal is immediately killed its brain is removed and sliced the slices are coated with a photographic emulsion After a few days in the dark areas of the brain that were particularly active show up as dark spots of radioactivity in vivo cerebral microdialysis measurement of specific neurotransmitters in living/behaving animals Immunocytochemistry Finds Neurotransmitters and Receptors Takes advantage of the immune reaction. Antibodies attempt to destroy foreign substances (antigens) Often by attaching themselves to the antigen. Antibodies for peptide neurotransmitters and receptors have been created by cell biologists. The antibodies are labeled with a dye or radioactive element and then used to identify specific neuroproteins in slices of brain tissue Crayfish brain stained with anti-serotonin antibody Localization of postsynaptic proteins in a cultured neuron by immunocytochemistry. Antibodies to the NMDA receptor are labeled Yellow. Glutamate acts at NMDA receptors The NMDA receptors are concentrated in the yellow patches along the dendrites. In situ hybridization locates peptides and proteins in the brain All peptides and proteins (including enzymes) are synthesized according to information contained on the chromosomes. mRNA carries the code for a protein of peptide from the DNA in the nucleus to the ribosomes. In situ hybridization labeled hybrid RNA strands with a base sequence complementary (opposite) to the mRNA for synthesizing the target neuroprotein are created The labeled RNA will attract its complementary mRNA The hybrid RNA binds to the complementary mRNA in the target cells This tells us where the protein or peptide that we are interested in is being produced. Labeled neurons in the hypothalamus – The tissue was exposed to labeled RNA that binds with mRNA for the synthesis of vasopressin (a peptide). BEHAVIORAL RESEARCH METHODS OF BIOPSYCHOLOGY Outline 1. Neuropsychological Testing 2. Paradigms of Animal Behavior a. General Tests: The WAIS b. lateralization of Language c. Specific Tests of Memory d. Specific Tests of Frontal Lobe Function a. Analysis of Species-Common Behaviors b. Traditional Conditioning Paradigms c. Seminatural Animal Learning Paradigms 3. Conclusion: Converging Operations WAIS Most neuropsychological assessments begin with the Wechsler Adult Intelligence Scale (WAIS) It has 11 subtests 6 comprise the verbal scale (e.g., digit span, information, similarities) 5 comprise the performance scale (e.g., block design, object assembly) The information subtest and the digit span test are memory tests that comprise part of the WAIS however, these are notoriously bad measures of memory.