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