Chapter 9: Kinds of Research

In this Chapter…

• Animal Research
• Sample Research Methods
• Imaging
• Gene Diagnosis

Animal Research

• Many vertebrate animal species are genetically and biochemically similar to humans
  • Without rats or mice, the role of neurotransmitters in cell communication would not be discovered
  • Rabbits and cats were very important models for studying vision and other senses
  • Zebrafish have transparent fertilized eggs, so they’re good models for developmental neuroscience research
• Invertebrates were also used to learn more about the human nervous system
  • Fruit flies have a less complex nervous system, but humans and they share many features
  • Sea Slugs were important for studying learning and memory

Chemical Connections in the Nervous System

• Studies on rats and mice led to synapse-targeted treatments for Parkinson’s & ADHD
• Staining techniques helped scientists look at pathways and connections to make road maps of brain connections
  • These techniques were then used in rodents, monkeys, and dead humans to understand more about chemicals and pathways that can be affected by disease
• Parkinson’s
  • Arvid Carlsson discovered that Parkinson’s was caused by the depletion of dopamine using rabbits & mice
  • Scientists discovered that dopamine was most concentrated in basal ganglia with pigeons
  • Researchers concluded Parkinson’s causes cells in basal ganglia to die
  • Limits production of dopamine
  • Led to the discovery of Levodopa
    • Levodopa: a drug that gets converted to dopamine in the brain
• Studies with rats were helpful in discovering changes in the brain because of drug addiction
  • The first step was determining whether nonhuman species could be addicted to drugs
  • Experiments showed that when rats were given free access to the same drugs humans become addicted to, rats also take these drugs compulsively
• Other studies show that the part of the brain affected by drugs is the reward pathway
  • Especially the dopamine neurons of the ventral tegmental area (top of the brainstem)
  • Ventral tegmental area communicates with the nucleus accumbens (next to bottom of midbrain)
• The reward pathway is also activated by natural rewards (food, water, etc.)
  • Drugs can mimic or block the function of neurotransmitters in this pathway
  • Drugs can affect brain systems concerned with learning and memory

Learning and Memory

• Eric Kandel did work on learning and memory
  • Started investigations on mammals, but found that they were too complex
  • Then he turned to a simpler organism- the sea slug
• Certain stimuli resulted in a more robust protective reflex
  • This was a form of learning for sea slug
  • This strengthened reflex could remain in place for days & weeks as short-term memory
  • Additional work showed that stronger synapses were responsible for the retention of information
• Long-term memories form in a different way
  • Stronger stimuli activate genes resulting in an increase of some proteins and a decrease in others
  • This ultimately leads to the growth of new synapses
• After demonstrating that both short and long-term memory in sea slugs involve synapses, Kandel was able to show that same thing in mice and other mammals

Understanding Critical Periods

• Experiments with monkeys and cats determined treatment for amblyopia has the best outcome when started before age 8
  • Amblyopia: the vision of one eye is greatly reduced because the eyes do not work well together
• During the critical period, visual experiences guide the development of visual circuitry
• Mice are being used to understand what factors change after a certain age to prevent rewiring

Sample Research Methods

• Microdialysis: a research method used to measure the amount of a certain brain chemical found in a specific area of the brain
  • After the discovery of chemicals transported within neurons, methods have been developed to visualize brain activity and precisely track nerve fiber connections within an animal’s nervous system
  • This can be done by injecting radioactive amino acid into brain cells
  • This allows nervous system activities to show up on film
  • Another technique is the injection of horseradish peroxidase in nerve fibers
  • This can later can be identified under microscope
• Electrophysiology: the study of electrical properties of neurons
  • The discovery of action potentials, neuron communication, and long-term potentiation relied on this technique
  • It’s also used to diagnose some conditions
  • Hearing loss is assessed in infants through electrophysiological recordings of auditory brainstem responses to sound
    • Electrodes are placed on the head
    • They make recordings that are processed by computers
    • The computer makes analysis based on the time lapse between the stimulus and response
  • Electroencephalogram (EEG): electrodes are placed on the head and record the electrical activity of the brain in response to a variety of stimuli and activities

Imaging

Positron Emission Tomography (PET)

• Positron Emission Tomography (PET): a scanning technique based on the detection of radioactivity emitted when positrons undergo radioactive decay in the brain
  • Positrons: positively-charged anti-electrons
  • Small amounts of a radioisotope are introduced to the blood
  • The blood carries it to the brain
  • The radioisotope shows up in the brain in proportion to how hard local neurons are working
  • Computers make 3D images of changes in blood flow based on the amount of radiation emitted in a region of the brain
  • More brain activity produces a more vivid picture
• PET studies helped scientists understand more about how drugs affect the brain and what happens while people are working on different activities (learning, language)
  • PET scans are also helpful in understanding brain disorders (stroke, depression, Parkinson’s)
• PET allows scientists to measure the changes in the release of some neurotransmitters
  • Can be used to pinpoint the relationship between a particular neurotransmitter and behavior or cognitive process.
• SPECT (single photon emission computed tomography)
  • Less expensive but not as detailed
  • Tracers break down at a slower rate and do not require a nearby particle accelerator

Magnetic Resonance Imaging (MRI)

• Magnetic Resonance Imaging (MRI): a non-invasive scanning technique that provides a high-quality 3D image of organs and structures
  • Shows when structural abnormalities first appear in the course of disease & how they affect subsequent development
• The patient is exposed to a steady magnetic field
  • Different atoms in the brain resonate to different frequencies of magnetic field
• The background magnetic field lines up all the atoms in the brain
• A second magnetic field that is oriented differently from the background one is turned on and off many times a second at certain pulse rates
  • Particular atoms resonate to and line up with the second field
• Atoms swing back to the background field when the second one is switched off
  • This is picked up as a signal and converted into an image
  • Tissue with lots of water and fat looks bright white
  • Tissue with little to no water appears black
• Diffusion Tensor Imaging: takes advantage of diffusion rates of water and shows connections in the brain
• MRIs reveal the precise extent of tumors fast and vividly
  • They provide early evidence of potential damage from stroke

Magnetic Resonance Spectroscopy (MRS)

• Magnetic Resonance Spectroscopy (MRS): uses the same machinery as an MRI but measures the concentration of specific chemicals in different parts of brain
• Measures molecular and metabolic changes in the brain
• Provided new information about brain development, aging, Alzheimer’s, schizophrenia, autism, stroke
• This is a non-invasive technique

Functional Magnetic Resonance Imaging (fMRI)

• Functional Magnetic Resonance Imaging (fMRI): compares brain activity under resting and active conditions
• fMRI combines the standard MRI with a strategy for detecting increases in blood oxygen levels when brain activity brings fresh blood to a particular area of the brain
  • Increased blood oxygen in the area is directly correlated with neuronal activity
• This allows for more detailed maps of brain areas underlying mental activities
• fMRIs show detailed information about areas of brain activity while the individual is engaged in a particular task

Magnetoencephalography (MEG)

• Magnetoencephalography (MEG): reveals the source of weak magnetic fields emitted by neurons
• MEG can characterize changing patterns of neural activity down to milliseconds
  • By presenting stimuli at various rates, scientists can determine how long neural activation is sustained in brain areas that typically respond
• MEG can combine the information obtained from fMRI and MEG
  • MEG shows when certain areas become active while an individual is performing a task

Optical Imaging and Other Techniques

• Optical imaging: relies on shining weak lasers through the skull to see brain activity
  • Techniques are inexpensive, relatively portable, and silent
  • This can be used on infants
• Near-infrared spectroscopy (NIRS): shining lasers through the skull at near-Infrared frequencies
  • Renders the skull transparent
  • Blood with oxygen in it absorbs different frequencies of light than blood in which oxygen has been consumed
  • Observation of how much light reflected back shows blood flow
• Diffuse optical tomography: used to create brain activity maps
  • Event-related optical signal: records how light scatters in response to fast cellular changes that arise when neurons fire
• Transcranial magnetic stimulation (TMS): induces electrical impulses in brain by altering magnetic fields through an electromagnetic coil held against the scalp that emits powerful magnetic pulses
  • Repetitive TMS is used to investigate the role of specific brain regions during behavior
  • Information from TMS and fMRI can show the correlation between a brain region and behavior

Gene Diagnosis

• Genes: sections of DNA that code for a product
• DNA is made up of the bases Adenine (A), Cytosine (C), Guanine (G), and Thymine (T)
  • DNA strands are long, spiraling, double helixes arranged in 46 chromosomes
  • The entire genome is made of about 40,000-50,000 genes
  • We have one copy of every gene from mom and another one from dad
  • We pass down one copy to children and so on
• 7000+ disorders suspected to have genetic origins
  • Mutations: errors in the sequence and/or amount of DNA
  • Mutations prevent genes from functioning properly and can contribute to disease
• Chromosome microarrays: look carefully at the overall chromosome makeup of a person and find out if segments of chromosomes or missing or duplicated

Tracking Down Genes

• Early mapping techniques allowed scientists to track down genes responsible for many neurological conditions
• HTT: gene altered in Huntington’s patients
• RBI: gene that causes retinoblastoma
• DMD: gene thatcauses Duchenne muscular dystrophy
• FMRI: gene that is abnormal in those with fragile X syndrome
• 22q deletion syndrome: individuals are missing a part of chromosome 22
  • People with 22q deletion syndrome have a higher chance of developing mental illness
• Sometimes, genes passed to an infant can undergo changes in the infant
  • So the infant has a genetic alteration that was not found in either of the parents
• LIS1: helps to tell the brain how to grow
  • People with mutations in this gene have smoother brains than normal
  • May have seizures
  • Severe intellectual disability is common
  • Parents do not have mutations in the same gene
• TSC1 and TSC2: cause tuberous sclerosis complex
  • Tuberous sclerosis complex: a genetic disorder characterized by the growth of many benign tumors in the body
• MECP2: causes Rett Syndrome
  • Rett syndrome: a rare neurodevelopmental disorder that affects the way the brain develops
• Deletion of a portion of chromosome 16 can lead to many neurological symptoms
• “Next-generation” sequencing is expected to uncover the function & sequence of all 20,000+ genes (exome)
  • The other non-coding associated DNA is thought to influence or regulate genes
  • Exome + associated DNA= genome
• MLL2: causes Kabuki Syndrome
  • Kabuki syndrome- a rare, multi-system that is characterized by many different abnormalities including skeletal abnormalities, short stature, and varying levels of intellectual disability