13A. Kinds of Research

Question 1

When were we first able to observe neurons, and how?

Answer 1

Late 19th century. Used histological techniques that start with a very thin slice of brain tissue to which stains area applied to add contrast or colour. Tissue is then viewed with a light microscope

Question 2

Histology

Answer 2

Study of how cells form tissues. Histological techniques can reveal changes in density of cell types or presence of molecules that suggest a disease. Have helped illuminate brain changes underlying disorders. E.g., showed that an enzyme that breaks down acetylcholine is associated with Alzheimer’s. In Parkinson’s, revealed the death of neurons that normally control movements through dopamine signalling

Question 3

When and how was it discovered that neurons are individual cells?

Answer 3

1950s using electron microscopy

Question 4

What technique was used to map the pathways by which information travels from the eyes to the visual cortex?

Answer 4

Radioactive tracers

Question 5

MRI

Answer 5

Magnetic resonance imaging: developed in 1980s. Uses radio waves and strong magnets to create images of brain based on distribution of water within its tissues. Can tell the difference between grey and white matter. Grey matter consists of cell bodies, dendrites, and synapses of neurons, white matter mostly contains axons wrapped in myelin. Based on distribution of water, MRI images clearly differentiate between cerebrospinal fluid, water-rich cells of grey matter, and fatty white matter

Question 6

Electrophysiology

Answer 6

Measure changes in electrical charge of individual neurons. Thin glass electrode placed in a neuron to measure voltage across membrane. Can be used on live animals or a slice of brain kept alive in a Petri dish. Used to make discoveries about synaptic plasticity (capacity of synapse to become stronger or weaker in response to sensory inputs). E.g., repeatedly stimulating a neuron by training an animal in a task or by electrical stimulation increases synaptic strength and chance that a downstream neuron will react to the incoming signal

Question 7

Disadvantage of electrophysiology and an alternative technique

Answer 7

Invasive. Alternative: EEGs

Question 8

EEG

Answer 8

Electroencephalography. 20 thin metal disks are placed on the scalp, each disk is connected by wires to a machine that records activity of neurons close to brain surface. Used to understand epilepsy and stages of sleep, but does not provide information at level of individual neurons

Question 9

Two-photon microscopy

Answer 9

Lab animal is genetically modified so that some of its neurons produce a protein that glows when a laser beam shines on them. Used to look at individual neurons in a living brain

Question 10

Mapping gene locations

Answer 10

Another trait with a known location that tend to be linked to the trait of interest must be identified. Narrows down the target gene’s location

Question 11

Identification of variations in copy number

Answer 11

Use DNA chips or microarrays. Each spot on array contains a known gene, which can grab onto corresponding bits of the genome being analyzed. Can be used to compare DNA samples of two people, one healthy and one with a disorder, to see if certain pieces are repeated more. Another type of microarray helps researchers determine if a patient has a chromosomal translocation. Useful in Huntington’s disease

Question 12

CRISPR

Answer 12

Clustered regularly interspaced short palindromic repeats

Question 13

Optogenetics

Answer 13

Controls brain activity with flashes of light. Genetically modify an animal so that its neurons produce a light-responsive protein. Optical fibres inserted into brain allow light to shine on those neurons, either activating or silencing them. Used to understand how neurons work together in circuits. Used to control behaviours ranging from sleep to addiction.

Question 14

Lissencephaly

Answer 14

Brain malformation, surface of brain is smooth. Babies start having spasms and develop drug-resistant epilepsy and severe intellectual + motor disabilities. 70% of these patients have mutations in L1S1 gene

Question 15

Kabuki syndrome

Answer 15

Intellectual disabilities, distinctive facial appearance, slow growth. Most have mutations in KMT2D gene

Question 16

Fragile X syndrome

Answer 16

Most common form of congenital intellectual disability in males. Caused by excessive number of CGG repeats in FMR1 gene. Not everyone exhibits symptoms, but they are carriers

Question 17

3 notable animal models

Answer 17

Aplysia (sea slug): used to study learning and memory

Fruit fly (drosophila): used to study how genes control behaviour

Mice: used to study addiction

Question 18

Microdialysis

Answer 18

Monitor neurotransmitters in action. Tiny tubes inserted into brain, collect liquid from just outside neurons and analyze it. E.g., analyze liquids captured during learning to identify molecules involved in the process. Can also be used to deliver compounds to brain.

Question 19

fMRI

Answer 19

Detects blood flow and differences in oxygen-rich vs oxygen-poor blood based on idea that more active regions need more oxygen/nutrients. Indirect view of neuron activity

Question 20

MEG

Answer 20

Magnetoencephalography. Detects electrical currents coursing through groups of neurons. When neuron activities are synchronized, their electrical currents produce weak magnetic fields that MEG can detect. Useful for detecting rapid changes in brain activity but doesn’t provide precise location of that activity. Can be combined with fMRI

Question 21

NIRS

Answer 21

Near-infrared spectroscopy. Like fMRI, monitors flow of oxygenated blood. Only useful for measuring activity near surface of brain and isn’t as detailed. But it’s cheaper, more portable, and more comfortable for subject. Setup is just wearing a cap with wiring. Some wires transmit laser beams into brain while others detect light after it travels through brain. Can be used to determine extent of injuries or to monitor oxygen levels of patients under anesthesia.

Question 22

PET

Answer 22

Positron emission tomography. Tracers injected into blood. Could be oxygen, glucose, or a neurotransmitter. Tells you where the compound goes. Can detect amyloid plaques of Alzheimer’s

Question 23

TMS

Answer 23

Transcranial magnetic stimulation. Coil that generates magnetic field placed near head. Field can penetrate skull, temporarily activating or silencing a region of the cortex. Used to treat depression, anxiety, PTSD.

Question 24

Computational neuroscience

Answer 24

Branch of neuroscience that develops theories or models about how the brain processes information then tests those models against real-world data. E.g., examine data from EEG or fMRI, develop mathematical models to explain neuron activity.