Brain Bee Chapter 16 - Kinds of Research

histology

study of how cells form tissues

histological techniques → coloring a thin brain slice and observing it under a microscope
reveals density changes or molecule presence

ex: showed that acetlycholinase (enzyme that breaks down acetylcholine) is associated with Alzheimer’s
ex: showed that Parkinson’s patients have death of dopaminergic neurons

electron microscopy

produces detailed images of cellular structures by directing beam of electrons through thin slices of tissue

revealed that neurons are individual cells and not physically interconnected cell bodies (physically continuous)

radioactive tracers

map the signaling of pathways
used to map complex pathways for visual input (eyes→ visual cortex)

MRI

magnetic resonance imaging
uses radio waves & strong magnets to display water distribution in brain tissue → differentiate gray matter, white matter, cerebrospinal fluid

electrophysiology

measures changes in electrical charge of individual neurons

thin glass electrode is inserted into a neuron, measuring voltage
for rats & mice, too invasive for humans

can also be done in an isolated petri-dish neuron → for drug effects

revealed synaptic plasticity

EEG

electroencephalography

records human brain activity without invasive procedures

20 thing metal discs are placed on the scalp → records activity of neurons near the brain’s surface

helped understand epilepsy and sleep stages → no individual neuron information

genetic linkage studies

use known chromosomal location of a linked trait to better narrow down the likely location of a gene of interest

DNA chips / microarrays

used to identify variations in copy number of genes
DNA is arrayed in rows and columns on surface of chip, with each spot having a known DNA sequence → grab onto corresponding bits of analyzed genome

ex: Huntington’s Disease → HTT gene has 100+ repeats of DNA stretch, compared to the normal dozen (12)

→ can compare 2 DNA samples from different people, helps researchers determine if patient has chromosomal translocation

Human Genome Project

made most of human genome sequence public

CRISPR

clustered regularly interspaced palindromic repeats

evolved bacterial immune system that allows DNA-cutting enzymes or new bits of DNA to be inserted into animal models

ex: mimic Alzheimer’s disease in rodents, observe mutations that cause autism, Parkinson’s, etc. in petri dishes

optogenetics

use genetic modification to have a lab animal’s neurons produce light-responsive protein → optical fibers inserted into brain, either silencing or activating neurons

allowed better understanding of how neurons work together in circuits, used to control animal behaviors like sleep and drug addiction

epigenetics

parts of the genome that are not genes, but regulators of gene activity

study of this has helped clarify role of gene regulation in brain development and learning / how mutations in regulatory regions cause disease

Lissencephaly

brain malformation where surface of brain is smooth
babies have spasms, develop drug-resistant epilepsy and severe intellectual and motor disabilities

70% of patients have mutation in LIS1 gene
other mutations also associated with the condition

Kabuki syndrome

symptoms: intellectual disability, distinctive facial appearance, slow infancy growth, physical problems

patients may have mutation in KMT2D gene / other similar genes

Fragile X syndrome

most common form of congenital intellectual disability in males

caused by excessive number of DNA sequence (CGG) repeats within FMR1 gene

some with elevated repeats may be unaffected, but are carriers with risk of passing it on to their children

Aplysia

sea slug

only 10,000 neurons, with some being visible to the naked eye
exhibits simple behaviors that can be modified with training

helped reveal principles of learning and memory → timing of training sessions in learning, molecules that strengthen synapse

Drosophila

fruit fly

used to study how genes control behavior

foraging gene → roam or sit while eating
timeless gene → non-normal circadian rhythms

rats

used to study addiction related behavior and genetics of more resistant breeds

microdialysis

thin tubes are inserted into brain to collect tiny volumes of liquid and analyze it

used for identifying neurotransmitters and molecules that are important for a certain process

used for delivering compounds to brain for studying drugs

pharmacology

study of effect of drugs → uses microdialysis

mass spectrometry

compounds in a sample are ionized (given electrical charge) and sent through electric or magnetic field

behavior of each molecule indicates its mass → provides clues for identifying a molecule

used to identify location of brain where a side effect (involuntary movements, other severe side effects) of Parkinson’s treatment acts

fMRI

functional MRI

uses MRI to detect differences in oxygen-rich vs oxygen-poor blood, showing brain activity in fairly small regions (active regions need more oxygen full blood)

indirect view of neuron activity, but can pinpoint brain activity to fairly small regions

good spatial resolution
not as good temporal resolution compared to MEG

MEG

magnetoencephalography

detects actual electrical currents coursing through groups of neurons (synchronized = detectable magnetic fields)
uses helmet-shaped device

good temporal resolution (detecting rapid changes)
bad spatial resolution (precise location of those changes)

NIRS

near-infrared spectroscopy

similar to fMRI by monitoring flow of oxygenated blood for estimating neuron activity BUT NIRS is only useful for measuring activity near the surface of the brain

much less expensive than fMRI and portable

individual wears cap with wiring hooked to it that transmits laser beams, cap detects light after it travels through brain

used to monitor oxygen levels of patients under anesthesia, determine extent of brain injuries, and for studying brain activity during tasks not possible in an MRI machine

PET

positron emission tomography

detects short-lived radioactive compounds injected in the bloodstream

can indicate blood flow, regions affected by a certain neurotransmitter, or amyloid plaques

good temporal resolution (like MEG), poor spatial resolution (unlike MRI)

TMS

transcranial magnetic stimulation

coil that generated magnetic field is placed near head, temporarily activating or silencing regions of cortex

used to treat psych disorders (anxiety, depression, PTSD), option for medication-resistant patients

computational neuroscience

researchers develop theories or models about how brain processes information, and then tests these models against real-world data