AA

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