Chapter 1 Flashcards
Historical Overview Scientific Method Research Ethics
Neuroscience:
Multidisciplinary study of the nervous system
Behavioral Neuroscience:
Branch of psychology that studies the relationship between the brain and behavior
List the 8 Interconnected Levels of Analysis
Social, organ, neural system, brain region, circuit, cellular, synapse, and molecular levels
Trepanation
Trepanning, also known as trephination, trephining or making a burr hole, is a surgical intervention in which a hole is drilled or scraped into the human skull, exposing the dura mater to treat health problems related to intracranial diseases. It may also refer to any “burr” hole created through other body surfaces, including nail beds. It is often used to relieve pressure beneath a surface. A trephine is an instrument used for cutting out a round piece of skull bone.
Name the oldest known medical writing
Edwin Smith Surgical Papyrus (Ancient Egyptians)
Hippocrates quote from On the Sacred Disease
Men ought to know that from nothing less but the brain comes joys, delights, laughter, sorrows, grief, despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear …And by the same organ we become mad and delirious, and fears and terrors assail us…All these things we endure from the brain when it is not healthy.
Galen
(130-200 AD)
Performed animal dissections and studied gladiator injuries.
Believed that the nervous system was a network of fluid-filled, interconnected tubes and chambers. Fluid in ventricles plays important role in transmitting messages to and from the brain.
Luigi Galvani
(1737-1798)
Showed that the nervous system operated by electrical transmission, disproving the pineal gland ventricle ideas.(1780)
Stimulated frog’s legs using electricity
Emil du Bois-Reymond (1818-1896)
(1818-1896)
Electricity and the nervous system
Emil du Bois-Reymond was a German physician and physiologist, the discoverer of nerve action potential, and the father of experimental electrophysiology.
Studied Spinal Reflexes
–Francois Magendie: 1783-1855
–Charles Bell: 1774-1842
Spinal cord has two parallel pathways
–Sensory Nerves
–Motor Nerves
Camillo Golgi’s Neuron theory
nervous system consists of vast interconnected web of continuous fibers
Santiago Ramon y Cajal’s Neuron theory
nervous system composed of array of separate independent cells. Cajal won (mostly). Established the Neuron Doctrine. Not proven until development of Electron Microscope in the 1950s.
Phrenology
–Franz Josef Gall
–Johann Casper Spurzheim
Deducing brain function and personality through analization of the bumps on the skull.
Pseudoscience
Localization of Function
Phineas Gage
Gage’s Personality Before the Accident that damaged his Frontal Lobe:
- responsible
- intelligent
- socially well-adapted
Gage’s Personality After the Accident (1848):
- intelligence, speech, learning, movement intact
- no sense of responsibility
- no respect for social conventions
- profane
- irreverent
“The equilibrium between his intellectual faculty and animal propensities had been destroyed.”
- Gage’s physician
“Gage was no longer Gage.” - Gage’s friends
Localization of function.
Localization of Function
Phineas Gage (1848)
Broca (1861) localization of language, “Broca’s area”
Fritsch and Hitzig (1870) localization of motor function in the cortex
Fritsch and Hitzig
localization of motor function in the cortex (1870)
Did experiments on live animals; would electrically stimulate part of the brain to see what its function was.
Broca
localization of language, “Broca’s area” (1861) Producing speech (but not understanding it)
Empiricism
use direct observation.
The philosophical theory that all knowledge is derived from sense-experience.
Stimulated by the rise of experimental science, it developed in the 17th and 18th centuries, expounded in particular by John Locke, George Berkeley, and David Hume.
What is Science?
Method of acquiring knowledge
“If it were not for observation, there would be little reason for choosing between scientific theories and fictional accounts, between science and pseudoscience, between warranted assertions and fanciful hopes.” -(Martin, 1972)
The 4 Types of Observation
- Naturalistic observation
- Case study
- Survey
- Experiment
Theory
integrates and interprets many observations to explain a phenomenon.
No “Final Answers”
Hypothesis
Testable (yes/no) prediction that is used to guide further research.
No “Final Answers”
Correlational Studies
Systematic research design that does not manipulate but rather observes whether two variables are connected
Confounding Variable
an extraneous variable in a statistical model that correlates with both the dependent variable and the independent variable.
refers to a variable which the researcher cannot control or eliminate so that it does not damage the internal validity of an experiment.
Experimental Group:
Receives the manipulation
Control Group:
Does not receive the manipulation
What is an Experiment?
Research Design characterized by:
–Random Assignment
–Control of extraneous/confounding variables
–Manipulation of a condition
–Measurement of changes from the manipulation
–Independent variable (IV) • manipulation of a condition •e.g. exercise –Dependent variable (DV) •measurement of changes from the manipulation •e.g. weight loss
Experimental Designs
- Unlike correlational designs, they permit cause and effect inferences
- May lack generalizability from lab to real world
Research with Human Participants
- Must minimize pain, discomfort, risk
- Informed Consent
- Deception only if necessary
- Debriefing
- Institutional Oversight (IRB)
Reasons for Using Animals in Research
- Controlled environment
- Homogenous history
- Briefer development and lifespan
- Some experiments cannot ethically be completed in people
“Virtually every advance in medical science in the twentieth century, from antibiotics and vaccines to anti-depressant drugs and organ transplants, has been achieved either directly or indirectly through the use of animals in laboratory experiments” —American Medical Association (1992)
Animal Research Guidelines
- Institutional Oversight (IACUC)
- As few subjects as possible
- Humane Housing
- Careful attention to health & welfare
- Minimization of discomfort and stress
Neuroscience Research Focus
Structure:
How is it built?
How is it connected?
What does it look like?
Function:
How does it work?
What does it do?
Why is it important?
Computerized Tomography (CT)
•Uses multiple x-rays to construct a 3D image
•X-ray penetrates body and absorbed by various “radiopaque” tissues
•Digital reconstruction within plane of slice
Forms 3D image of brain by combining X-rays of cross sections of brain; images structure and damage
Good Temporal Resolution and Spatial Resolution
Positron Emission Tomography (PET)
•Injection of a radioactive substance
(2-deoxyglucose) into the bloodstream,
which is taken up by parts of the brain according
to how active they are.
•Baseline measure subtracted from activity during task
Image produced by emissions from injected substances that have been made radioactive; tracks changing activity, detects receptors, etc.
Horrible Temporal Resolution.
A little painful because of the injection.
Magnetic Resonance Imaging (MRI)
Magnetic field and radio waves used to produce high-resolution structural images of the brain
Measures variations in hydrogen concentrations in brain tissue; images structure and damage
Functional Magnetic Resonance Imaging (fMRI)
•Changes in blood flow and blood oxygenation in the brain (i.e., hemodynamics) are closely linked to neural activity
•Ratio of oxyhemoglobin to deoxyhemoglobin determines areas of brain activation
•Measures brain activation by detecting increases in oxygenenated blood directed at active neural structures
•BOLD: blood-oxygen-level-dependent signal
Detects increases in oxygen levels during neural activity; tracks changing activity
BOLD
blood-oxygen-level-dependent signal
List the 4 Brain Recording Methods
- Electroencephalography (EEG)
- Event Related Potential (ERP)
- Magnetoencephaolgraphy (MEG)
- Single cell recording
Electroencephalogram (EEG)
•Scalp electrodes provide information about the activity of large populations of neurons
•Used to study sleep and diagnose seizures
Sums electrical activity of neurons between two electrodes; detects fast-changing brain activity but is poor at localizing it
Great Temporal Resolution; Horrible Spatial Resolution
Event Related Potential (ERP)
- Series of EEG responses to environmental stimuli
* Useful in studies of perception, cognitive processes
Magnetoencephalography (MEG)
Brain’s magnetic output is assessed
Skull is transparent to magnetism, not electricity, making MEG less distorted than EEG
Localization of activity is possible
Neurophysiology: Extracellular Recording
- In vivo recording of electrical activity of one or more neurons
- Electrode located near, not within, neuron
- Correlate with behavioral/cognitive events
Neurophysiology: Intracellular Recording
–Brain slice ~0.5 mm wide
–Inject current, depolarizing neuron, causing Action Potential
Optogenetics
Optogenetics (from the Greek optos, meaning “visible”) is a neuromodulation technique employed in neuroscience that uses a combination of techniques from optics and genetics to control and monitor the activities of individual neurons in living tissue—even within freely-moving animals—and to precisely measure the effects of those manipulations in real-time. The key reagents used in optogenetics are light-sensitive proteins. Spatially-precise neuronal control is achieved using optogenetic actuators like channelrhodopsin and archaerhodopsin, while temporally-precise recordings can be made with the help of optogenetic sensors like Clomeleon and Mermaid.
Optogenetics is the combination of genetics and optics to control well-defined events within specific cells of living tissue. It includes the discovery and insertion into cells of genes that confer light responsiveness; it also includes the associated technologies for delivering light deep into organisms as complex as freely moving mammals, for targeting light-sensitivity to cells of interest, and for assessing specific readouts, or effects, of this optical control.
List the 3 Brain Manipulation Methods
- Brain stimulation
- Transcranial Magnetic Stimulation (TMS)
- Lesions
Brain Stimulation
- Delineate functional properties of neural tissue
- Olds & Milner: pleasure pathways
- “Ratbots” respond to stimulation by changing direction
Transcranial Magnetic Stimulation (TMS)
Applies strong and quickly changing magnetic fields to surface of skull that can interrupt
brain function
rTMS successfully used to temporarily change brain activity immediately below stimulation site
- Schizophrenia
- Depression
List 6 Types of Human Lesions
–Trauma –Strokes –Tumors –Infection –Toxins –Neurological disease
List 4 Types of Animal Lesions
– Ablation
– Heat / Electrolytic: kills both neurons and axons
– Neurotoxic: kills neurons but not axons
– Cooling (reversible inactivation)
Stereotaxic Surgery
Used to localize function
The 2 Brain Structure Methods
- Histology
* Tract tracing
Histology
Study of microscopic structure and tissue
Describe the 5 Steps of Histology
- Fixed by freezing or formaldehyde.
- Sliced thinly by a vibrating microtome or cryostat.
- Mounted on microscope slides.
- Stains applied to highlight structures of interest.
- Viewed with a microscope (e.g., Light, Confocal, Electron)
Nissl stain
Stains just the cell bodies of all neurons
Example: Cresyl Violet
Golgi stain
Stains single cells completely, Darkly stains full neuron, Randomly stains ~5% of neurons
Myelin stain
Stains myelin that wraps and insulates axons, Identifies neural pathways
Tract Tracing
•Anterograde
−“Moving forward”,
−Finding where a pathway ends
•Retrograde
−“Moving backward”
−Finding where a pathway begins
Diffusion Tensor Imaging
DTI allows direct in vivo examination of aspects of the tissue microstructure. DTI takes advantage of diffusion anisotropy to provide excellent details of the brain—e.g., it enables mapping of the orientation of the white-matter tracts.
List the 3 Neurochemical Methods
- Neuropharmacology
- Microdialysis
- Immunocytochemistry
Drugs
chemical substances that alter biochemical functioning
Receptor Antagonists
Inhibitors of neurotransmitter receptors
Receptor Agonists
Mimic actions of naturally occurring neurotransmitters
Neuropharmacology
In animals, drug infusion can be localized through use of guide cannula
Microdialysis
Procedure for analyzing chemicals (e.g., drugs, neurotransmitters) present in the extracellular fluid
–Small piece of tubing made of semipermeable membrane implanted in the brain, allowing CSF from subject to flow into probe for collection and analysis
Immunocytochemistry Involves What Proteins?
Immunocytochemistry uses antibodies attached to a dye to identify the presence of particular proteins, including: –Receptors –Neurotransmitters –Hormones –Enzymes
Antibody Binding: Immunocytochemistry
antibody attaches to antigen in fixed, mounted, brain tissue
Describe the 4 Steps of Immunocytochemistry
- Protein injected into animal to make antibodies.
- Blood containing antibodies removed.
- Antibody applied to tissue slices and tagged to make visible.
- Only neurons containing antigen are labeled.
The 2 Genetic Methods
- Twin studies
* Genetically modified animals
Twin Studies
Compare variable of interest between identical (monozygotic) and fraternal (dizygotic) twins.
Contribution of heredity is stated as concordance rate.
Genetically Modified Animals
Knockout or knockin genes
- Protein production blocked or added
In Vivi
vs.
In Vitro
In vivo (Latin for “within the living,”) is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro (“within the glass”, i.e., in a test tube or petri dish) controlled environment. Animal testing and clinical trials are 2 forms of in vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject.
François Magendie
1783-1855
Made great contributions to experimental physiology, pharmacology and pathology.
His pioneer studies of the effects of drugs on various parts of the body led to the scientific introduction into medical practice of such compounds as strychnine and morphine. In 1817 along with Pierre Joseph Pelletier, he isolated emetine. In 1822 he confirmed and elaborated the observation by the Scottish anatomist Sir Charles Bell (1811) that the anterior roots of the spinal nerves are motor in function, while the posterior roots serve to communicate sensory impulses. In 1825 he gave one of the earliest descriptions of the cerebrospinal fluid.
Sir Charles Bell
(1774-1842)
Scottish anatomist whose New Idea of Anatomy of the Brain (1811) has been called the “Magna Carta of neurology.” He received a medal from the Royal Society; he was knighted. He returned to Edinburgh in 1836 to accept the chair of surgery at the university.
Bell’s research on the anatomy of the brain resulted in an expanded volume, entitled The Nervous System of the Human Body (1830). Bell distinguished between sensory nerves that conduct impulses to the central nervous system and motor nerves that convey impulses from the brain or from other nerve centers to a peripheral organ of response. He announced that the anterior roots of the spinal nerves are motor in function, while the posterior roots are sensory—an observation that was experimentally confirmed and more fully elaborated 11 years later by François Magendie.
Functional
Changing over time
Structural Methods
CT and MRI
