Neuro Lab Week 2 - Kinds of Research

Histology (anatomy)

-study of how cells form tissues

-can reveal changes in density of cell types or presence of molecules that can suggest a particular disease

-helped show brain changes underlying some neurodegenerative disorders

-pass visible light through tissues

Alzheimer’s

-associated with enzyme breaking down acetylcholine shown by histological methods

electron microscopy

-produces detailed images of cell structures magnified 100,000s of times

-directs beam of e- through thin tissue slices and enlarges/focuses image with electromagnetic lenses

-revealed that neurons are individual cells

injecting radioactive molecules/tracers

-method for mapping signaling pathways in neural networks

-monitor radioactive movement down axon

MRI

-view detailed image of brain structure

-uses radio waves & magnets to create images based on distribution of water in tissues

-tell difference btwn gray & white matter

electrophysiology

-measure changes in electrical charge of individual neurons (=firing)

-thin glass electrode placed inside a neuron to measure voltage across cell membrane

-measure neuron activity in lab animals or keep slice of brain “alive” in proper environment

-invasive

synaptic plasticity

-big discoveries from electrophysiology

-capacity of synapse to strengthen or weaken in response to sensory inputs

EEG

-record activity of neurons near brain surface

-non invasive

-discs on scalp

-useful for understanding epilepsy & sleep stages

-no info on individual neurons

two-photon microscopy

-look at individual neurons in brain

-lab animal genetically modified so some neurons produce protein that glows when laser beam shines

-understand changes in brain during normal processes & diseases

genetic linkage studies

-map gene locations

-ID another trait with a known location that tends to be linked with trait of interest

-helps ID genetic basis of disorders

Huntington’s Disease

-overabundance of copies/repeats of a stretch of DNA

-HTT gene

DNA chips/microarrays

-used to ID variations in DNA copy number

-array of spots on surface of chip; each spot contains known DNA sequence/gene & can grab onto corresponding bits of genome being analyzed

-compare DNA repetition btwn people

-can help determine chromosomal translocation

CRISPR

-evolved as bacterial immune system that targets viral invaders

-gathered its components to focus on specific DNA sequences

-recreate mutations or insert new bits of DNA by tethering DNA-cutting enzymes to this targeting system

-can mimic Alzheimer’s in rodents

-used to study mutated human neurons in Petri dishes

Optogenetics

-control brain activity with flashes of light

-genetically modify animal so neurons produce a light-responsive protein

-optical fibers then inserted into brain to allow light to shine on neurons, activating or silencing them

-helps show how neurons work tg in circuits

-helps control behavior

-discovered that green algae detect light using proteins/ion channels called channelrhodopsins, similar to those found in retina

-light can open these channels to excite neurons

-turn neurons on by shining a light & map neural circuits

-can also turn neurons off with light-activated pump (found in a bacteria)

non-genetic DNA sequences/regulatory regions

-regulate gene activity

-help det. conditions a gene is expressed or repressed

-these epigenetic changes occur when chemical tags are placed on regulatory region & influence whether genes will turn on or off

Lissencephaly

-brain malformation where surface of brain is smooth

-affects development

• spasms

• epilepsy

• intellectual & motor disabilities

-most patients have mutation in LIS1 gene, but other mutations are associated with condition

Kabuki syndrome

-intellectual disabilities

-distinctive face

-slow growth in infancy

-hard to diagnose bc symptoms range in severity

-most have mutations in KMT2D gene

Fragile X Syndrome

-excessive number of DNA sequence (CGG) repeats in FMR1 gene (synapse function)

-most common intellectual disability in males

-can have this mutation with no outward signs

Aplysia

-animal (slug) with relatively few neurons, but some are large enough to see with naked eye

-exhibit simple behaviors that can be modified with training

-helped scientists uncover many principles of learning and memory

• how timing of training sessions affect learning

• ID molecules that strengthen synapses so neural response is greater

Drosophila

-fruit fly used to study behavior/how genes control behavior

-mutations have been ID that affect full range of behaviors

Microdialysis

-monitor neurotransmitters in action

-insert thin tubes into brain, then collect & analyze liquid from just outside neurons

-can also be used to deliver compounds to brain

mass spectrometry

-ionizes compounds of a sample, then sent through an electric or magnetic field

-behavior of each molecule in the field indicates its mass

-useful in exploring neurodegenerative disorders (ID location of side effects)

fMRI

-detects blood flow & differences in oxygen-rich (more active) vs. oxygen-poor blood

-more active regions of brain need more oxygen & nutrients

-indirect view of neuron activity

magnetoencephalography (MEG)

-detects electrical currents coursing through groups of neurons

-synchronized neuron activities produce weak magnetic fields MEG equipment can detect

-helmet shaped device

-useful for temporal resolution, but not good spatial resolution

-can combine MEG high speed readings with fMRI anatomical data

NIRS (near-infrared spectroscopy)

-monitors flow of oxygenated blood to estimate neuron activity (like fMRI)
-differences:

• only useful for activity near surface of brain

• not as detailed

• less expensive

• more comfortable & convenient/portable (cap with wires)

-used to det. extent of brain injuries & monitor oxygen levels of patients under anesthesia

PET

-detects/traces short lived radioactive compounds (oxygen, glucose, neurotransmitter) that have been injected into bloodstream

-can detect amyloid plaques that are a hallmark of Alzheimer’s

-good temporal resolution, lacks spatial resolution

temporal resolution

detect rapid changes in brain activity

spatial resolution

detect precise location of brain activity

TMS

-coil generating a magnetic field placed near person’s head

-psychiatric disorders

EEG

-shows diff brain regions have diff rhythms

-generations of these patterns at level of neural circuits is not well understood

computational neuroscience

-helps bridge findings from microscopic to whole-brain level

-develop theories/models about how brain processes info, then tests models against real-world data

neurological/psychiatric disease afflict

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