L08 Flashcards

1
Q

What is experimental ablation (lesion study)?

A

Experimental ablation involves the removal or destruction of a portion of the brain. Presumably, the functions that can no longer be performed following the surgery are the ones the brain region normally controls.

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2
Q

What is an excitotoxic lesion?

A

Brain lesion produced by intracerebral injection of a glutamate receptor agonist, such as kainic acid. These drugs cause so much excitation (and calcium influx) that the affected neurons often undergo apoptosis, while axons passing through (fibers of passage) are usually spread.

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3
Q

What is a sham lesion?

A

“Placebo” procedure that duplicates all steps of producing brain lesion except for one that actually causes extensive brain damage.

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4
Q

What is a reversible lesion?

A

“Placebo” procedure that duplicates all steps of producing brain lesion except for one that actually causes extensive brain damage.

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5
Q

What is reversible lesion?

A

A temporary brain “lesion” can be achieved by injecting drugs that block or reduce neural activity in a given region. Common drugs include…
-Voltage-gated sodium channel blockers (stops all action potentials)
-GABA receptor agonists (which hyperpolarize cell bodies)

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6
Q

What are microelectrodes?

A

Thin metal wires with a fine tip that can record the electrical activity of individual neurons (known as single-unit recordings).

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7
Q

What does electric stimulation?

A

Electric stimulation involves passing an electrical current through a wire inserted into the brain. This will affect everything in the area (cell bodies and fibers of passage). Some electrical stimulation patterns (often very high frequencies), counterintuitively, tend to produce the same behavioral effects as lesioning the brain area.

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8
Q

What is chemical stimulation?

A

Chemical stimulation is achieved with drugs. In rodents, drugs are often administered through a guide cannula (hollow tube) implanted in a particular brain region. Anesthetics can be injected to shut down all neural activity. Alternatively, receptor agonist/antagonist can be used, which should not affect fibers of passage (i.e., axons just passing through the area), since there are no neurotransmitter receptors on the membrane in the middle of an axon.

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9
Q

What are optogenetics?

A

The use of light to control neurons which have been made sensitive to light through the introduction of foreign DNA. This foreign DNA encodes light-sensitive proteins known as opsins. Opsins are proteins that are sensitive to light.
The opsins we have in our eye are metabotropic receptors that operate with a 30-millisecond delay. The opsins we use for optogenetics are often ion channels that open and close instantly in response to light. The original ones were discovered in bacteria in different parts of the world. Recently people have started to intelligently design and modify opsins for research purposes.

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10
Q

What does retrograde labeling trace?

A

Afferent neurons.
What brain areas send their axons here? Retrograde labeling is used to label the cells that innervate (project to) a given region.

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11
Q

What does anterograde labeling trace?

A

Efferent neurons.
Where do the axons from these cells go? Anterograde labeling is used to label where axons from a particular location go to.

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12
Q

What is an example of a chemical used for retrograde labeling?

A

Fluorogold.
Fluorogold molecules are taken up by axon terminals and transported back to the cell body

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13
Q

What is an example of a chemical used for anterograde labeling?

A

PHA-L
PHA-L molecules are taken up by cell bodies and transported down to axon terminals.

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14
Q

What is stereotaxic surgery?

A

A surgical intervention that uses a stereotaxic apparatus. This is a device that permits a surgeon to put something into a very specific part of the brain.
It is used to inject things into the brain, such as drugs, viruses, or tracer molecules (dyes).
It is also used to permanently implant things, like cannula, electrodes, or fiber optic cable.

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15
Q

What is the bregma?

A

The junction where pieces of skull fuse together. Bregma is often used as a reference point for stereotaxic brain surgery.

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16
Q

Stereotaxic surgery is commonly used for one time injections of drug or virus to do what?

A
  1. Lesion a brain area (e.g. excitotoxic lesion)
  2. Lesion a specific type of cell in a particular brain area (e.g. inject a compound that specifically kills dopamine neurons)
  3. To change gene expression (e.g. to remove a gene needed for serotonin synthesis or to deliver DNA that encodes a foreign protein). This is typically accomplished with viral-mediated gene delivery.
17
Q

Other than injections, what is stereotaxic surgery used for?

A
  1. Implant guide cannula (hollow tubes)
    to allow for later infusions of drugs.
    Ex: Temporary (or reversible) lesions can be made by infusing a local anaesthetic (ex: lidocaine) which blocks action potentials.
  2. Implant microelectrodes for stimulation or recording experiments.
  3. Implant fiber optic cables to allow for imaging or stimulation using optogenetic techniques.
18
Q

How do we measure fluctuations in neurotransmitter levels in behaving animals?

A

Microdialysis

19
Q

What is an electroencephalogram (EEG)?

A

A measure of electrical activity in the brain that uses macroelectrodes (metal discs) attached to the scalp.
It records the summed population-level activity of millions of neurons.
It can be used as a diagnostic tool, since specific patterns of EEG activity are associated with different states of consciousness, stages of sleep, and types of cerebral atrophy.

20
Q

What is Diffusion Tensor Imaging (DTI)?

A

An MRI technique that measures the direction and speed of the diffusion of water molecules. It is used to identify axon tracts. The colors indicate the direction of water molecule diffusion

21
Q

What is a Computerised Tomography (CT) scan?

A

A computer assisted X-ray procedure used to take a “photograph” of the brain. The patient lies with his head positioned in the centre of a large cylinder, and an X-ray beam (i.e., high energy electromagnetic radiation) is projected through the head to an X-ray detector. The X-ray beam is delivered from all angles. A computer translates the information received from the X-ray detector into a series of pictures of the skull and brain. The procedure is relatively cheap and fast, but the resolution is not great for soft tissue like brain.

22
Q

What is Magnetic Resonance Imaging (MRI)?

A

MRI uses strong magnetic fields (instead of X-rays). The patient lies in the centre of a large cylinder.
When a strong magnetic field is applied to the body, the spin of every hydrogen atom proton assumes a particular direction inline with the magnetic field. (The direction of a proton’s spin is inconsequential for the chemical reactions of life.)
Then, radiofrequency waves (i.e., low energy electromagnetic radiation) are administered to the body. This energy is absorbed by protons, changing the direction of their spin. These protons then emit their own radio waves when their spin immediately flips back to that determined by the magnet.
By triangulating where the emitted radio waves came from, the scanner can provide an estimate of the relative density of protons (hydrogen atoms) in each area of the body. (Hydrogen atoms are most prevalent in fat and water.) The result is a high spatial resolution, three-dimensional image of the brain.
Normal MRI scans primarily reveal the density of lipid molecules. This is because the settings of the magnet and the radiofrequencies delivered to the brain are optimized to detect the hydrogen atom protons of lipid molecules.

23
Q

What is Functional Magnetic Resonance Imaging (fMRI)?

A

fMRI uses a rapid series of MRI scans.
The amount of oxygen in blood distorts the local magnetic field.
With a series of MRI scans, it is possible to detect changes in blood oxygenation, which reflects blood flow and correlates with neural activity.
When a brain area is active, blood flow to that region quickly increases (~5s lag).
fMRI is popular because it doesn’t involve needles, surgery, or radioactivity. It provides both structural and functional information with decent spatial resolution (1 to 5 mm) and temporal resolution (several seconds).
Researchers are now trying to modify the fMRI technique to measure fluctuations in neurotransmitter signaling. This approach uses “enzyme-activated magnetic resonance contrast agents,” which are molecules that distort the magnetic field differently when they bind to neurotransmitter.

24
Q

What are Positron Emission Tomography (PET) scans?

A

PET scans involve injecting a person with a radioactive compound. Radioactive sugar molecules (like 2-DG) are commonly used to detect changes in energy use in the brain.
2-DG is similar to glucose, in that it is taken up by energy consuming cells in the body. However 2-DG is not broken down as easily as sugar is, so it stays around for hours.
The scanner identifies where radioactive 2-DG molecules are located over time.
The main disadvantage of PET scanners is their operating costs. For safety reasons, the radioactive molecules are designed to decay rapidly (over hours), thus they have to be made on site the morning of the experiment.
The PET approach of using 2-DG as a general measure of neural activity has been superseded by fMRI, but researchers still use PET with other radioactive tracers, like L-Dopa.
PET is also used to measure changes in the expression levels of neurotransmitter receptors across weeks. These studies use radioactive agonists/antagonists.

25
Q

What are radiofrequency lesions?

A

Small lesions that can be made by passing radiofrequency current through a metal wire that is insulated everywhere but the tip.
This electric current produces heat that burns cells around the tip of the wire.
The size and shape of the lesion is determined by the duration and intensity of the current.
A downside to this approach is that axons just passing through will also be burned.