Chapter 7 - Studying the Brain Flashcards
What was the silver lining of the “frozen” addicts case during the 70s?
- Development for animal models of Parkinson disease for study
- Barry Kidston accidentally synthesized MPTP but wanted MPPP
- This isomer broke down into MPP+ which is toxic
- Ended up killing a bunch of dopaminergic neurons in the substantia nigra
What’s histology?
- Branch of biology which studies the microscopic anatomy of biological tissues
What was learned during the contextual learning rat study?
- Discovered that the dentate gyrus neurons are necessary for contextual learning
What were the Morris swimming tasks?
- Rats must navigate a swimming pool to find hidden platform
- There were different variations to test specific types of spatial memory: (a) place learning task (b) matching-to-place task (c) landmark learning task
What was the purpose of the skilled reaching task?
- Wanted to assess deficits and recovery in animal models of stroke
- Rats ability to reach into slot and retrieve food
- Researchers would break down their movements and score them
What’s a stereotaxic apparatus?
- A surgical instrument permitting researchers/neurosurgeons to target a specific area of the brain
- Head is held in a fixed position, allowing for precise positioning of all brain regions relative to each other.
What was informative about Phineas Gage’s experience?
- Provided insight into the functions of the frontal lobe
Who was the first to use electrical stimulation to the brain?
- Canadian neurosurgeon Wilder Penfield during the 1950s
- Did it first on the cerebral cortex of humans with untreatable epilepsy
- Done on live patients cause brain has no pain receptors
- Able to do some brain mapping
What’s deep brain stimulation? Advantages/disadvantages?
- Electrodes implanted deep in brain to stimulate a targeted area with a low-voltage electrical current to facilitate behaviour
- Used for PD, depression, schizophrenia, OCD, epilepsy Etc.
- Disadvantages: May damage other tissues, and electrodes heat up
What’s transcranial magnetic stimulation (TMS)? Advantages/disadvantages?
- Advantages: Non-invasive, not super expensive
- Disadvantages: Doesn’t penetrate super deep
- Magnetic coil is placed over the skull to stimulate the underlying brain
- Used either to induce behaviour or to disrupt ongoing behaviour
- Magnetic field lines pull on ions and induce a current in the brain
What are the advantages/disadvantages of using drugs as a form of brain stimulation?
- Disadvantages: Must either pass through BBB or be administered through an indwelling cannula; poor temporal resolution
- Advantages: Can influence activity of specific neurons. Because drugs wear off over time, can study drug effects on learned behaviours (animal is its own control)
What effects do the drugs haloperidol and amphetamine have on rats?
- Haloperidol = reduce dopaminergic neuron functioning
- Amphetamine = increases dopamine activity
Genetic knock-outs vs. knock-ins?
- Knock-outs = loss of function via gene deletion or inactivation
- Knock-ins = gain of function via inserting or activating a gene
What’s CRISPR-Cas9?
- Bacterial defence mechanism for fending off viruses
- Acts as an all-purpose tool for cutting DNA in any cell
- Can be used for both gene inactivation and insertions, or to repair a mutated gene
- Cas9 is the protein that acts as a nuclease (enzyme that cuts DNA)
- Start with a strand of RNA that is complimentary to the gene of interest
What is optogenetics?
- Transgenic technique that combines genetics and light to control targeted cells in living tissues
- Works by expressing light-sensitive ion channels or pumps in specific target cells
- Selected neurons respond immediately when exposed to light
What are the opsins derived from microorganisms used in optogenetics?
- Channelrhodopsin-2 (chR2) = depolarizes membrane when exposed to blue-light via an ion channel
- Halorhodopsin (NpHR) = hyperpolarizes membrane when exposed to green-yellow light via an active pump
- Chloride must be actively pumped since the inside of the cell is already at its resting potential of -70mV
What are the advantages/disadvantages of optogenetics?
- Advantages: Very high spatial and temporal resolution
- Disadvantages: It’s irreversible
What’s electrophysiology?
- Measuring activity with microelectrodes
- Can be done intracellularly or extracellularly
What are the advantages/disadvantages of extracellular recordings?
- Advantages - Can record groups of neurons, requires less expertise, can be done on live animals
- Disadvantages - Less info yielded
What are the advantages/disadvantages of intracellular recordings?
- Advantages - can get info from a single neuron, high temporal and spatial resolution
- Disadvantages - harmful to cells, confine neurons to growing in dishes or slices of brain tissue
What’s an EEG?
- Measures brain activity by recording graded potentials from thousands of cells from electrodes on scalp
- Simple, non-invasive procedure
What features is an EEG able to detect?
1) The EEG changes as behaviour changes
2) An EEG recorded from the cortex displays an array of patterns, some being rhythmical
3) The living brain’s electrical activity is never silent even when person is asleep or comatose
What are event-related potentials (ERPs)?
- Complex EEG waveforms produced in response to a discrete sensory stimulus
- Since electrical “noise” is a problem (since electrodes are placed on scalp), a computer generates an average from raw EEG data
- A positive excitatory response is recorded from a dip in the EEG graphs since electrodes are measuring activity that is occurring outside the synapses which end up being negative ions
What are the advantages and disadvantages of ERPs?
- Advantages - Temporal resolution, non-invasive, relatively cheap
- Disadvantages - poor spatial resolution, limited depth
How does a CT (computed tomography) scan work?
- Narrow X-ray beams are passed through the brain at many different angles
- Images are combined with the use of computing and mathematical techniques to create a static 3D image of the brain
- Tomo- is Greek for slice
- high density tissue absorbs a lot of radiation, so lighter colours indicate high-density regions (filled with lots of water)
How does an MRI (magnetic resonance imaging) work?
- Produces a static, 3D image by passing:
1) A strong magnetic field through brain
2) This is then followed by a radio wave
3) Then the radiation that is re-emitted by the protons in the brain is measured - Images based on density of H protons in different brain regions. Also able to map water densities because of this
- H atoms behave like tiny bar magnets that can be aligned by a magnetic field
What are the advantages of an MRI?
- Can identify differences between white and grey matter
- Identify ventricles
- Spatial resolution
- Less harmful (not radiation)
What does functional brain imaging signify?
- Able to indirectly track brain activity through means such as the amount of blood, oxygen, and glucose flowing into the regions while brain is active
How does an fMRI work?
- When human brain activity increases, the increase in oxygen produced by increased blood flow exceeds the tissue’s need for oxygen (overcompensation occurs)
- Oxygen-rich hemoglobin is less magnetic than oxygen-poor hemoglobin (binds to/shields iron)
- Deoxygenated blood distorts surrounding magnetic fields, reducing the signal of protons in the near vicinity
- Causes less radiation to be re-emitted.
What are the advantages/disadvantages of fMRI?
- Advantages: Good spatial resolution
- Disadvantages: High cost and expertise required
How does a PET (positron emission photography) scan work
- Used to detect changes in blood flow by measuring changes in the uptake of radiolabelled compounds such as water or glucose.
- Radioactive “tracers” are injected, which collect in active tissues
- The positrons emitted from radioactively tagged water or glucose molecules are attracted to and collide with electrons in tissue, which produces gamma rays (high energy photons)
- This is followed by a PET subtraction procedure: Stimulation - control = difference remaining
What are the advantages/disadvantages of PET scans?
- Advantages: Good spatial resolution, can do multiple tracers at one time, more versatile than fMRI, relatively safe
- Disadvantages: Poor temporal resolution, high cost.
