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