Neurotechniques 2: structural exploration of the brain

Question 1

What is cranial trepanation?

Answer 1

• Boring holes in a skull
• Evidence goes back as early as 7000 years ago
• Purpose unclear: healing and/or ritual
• Some individuals survived multiple skull surgeries

Question 2

What is experimental ablation?

Answer 2

Consists of lesioning/ destroying a specific part of the brain to study its function

Question 3

How did scientists use experimental ablation to test shoaling behaviour in goldfish?

Answer 3

scientists tested in telencephalon was involved:
 Control group
 Group in which telencephalon was ablated
 Fish with ablated telencephalon did not swim with the rest and stood alone in a corner

Question 4

What is a stereotaxic atlas used to do?

Answer 4

Locate specific brain regions

Question 5

How does stereotaxic surgery take place?

Answer 5

• Head of animal held in place
• Electrode: electrical current used to destroy brain regions – produces heat that kill cells around the tip of electrode – not very specific
• Cannula: excitatory amino acids (e.g. kainic acid). Amino acid injected into region of brain. Amino acid then destroys neurones. More specific – only affects neurones in the region
• Sham lesion: a ‘placebo’ procedure that duplicates all the steps of producing a brain lesion except for the one that actually causes the brain damage

Question 6

What are histological methods?

Answer 6

a group of procedures (including fixing, slicing, staining and examining the brain) that aim to observe the location of the lesion

Question 7

What is the case of Phineas Gage?

Answer 7

• He was a railroad construction foreman in the US
• His employer regarded him as the most efficient and capable foreman in their employ
• He was preparing an explosive charge with a tamping iron when the powder exploded and propelled the tamping iron straight through his head
• The tamping iron penetrated his left cheek, ripped into his brain and exited through his skull
• He survived and remained conscious
• His employer did not take him back after the accident. He uttered ‘the grossest profanity’ and showed ‘little deference for his fellows’. He became violent and ‘uncontrollable’
• Neuroscience’s most famous patient because his case was the first to suggest a link between brain trauma and personality change

Question 8

What did Wilder Penfield do?

Answer 8

• Used electrical brain stimulation on awake patients for the treatment of epilepsy
• Penfield recorded the patient’s reaction when stimulating certain brain areas
• Using the information gained during many hundreds of brain operations to create functional maps of the cortex (surface) of the brain
• Dr. Penfield’s experiments in stimulating the cortex enabled him to develop a complete map of the motor cortex, known as the ‘motor homunculus’ (areas of hands and face on the cortex are large because we use them very often)

Question 9

What are electrical recording/ stimulation techniques?

Answer 9

• Electrophysiology: single/multiple cells
• Electroencephalogram
• Deep brain stimulation (DBS)

Question 10

What are brain imaging techniques?

Answer 10

• Computerised tomography (CT) – X-rays
• Positron Emission Tomography (PET) – radioactivity
• Magnetic Resonance imaging (MRI) – magnetic fields

Question 11

What is deep brain stimulation and what does it do?

Answer 11

• Involves implanting electrodes within certain areas of the brain
• The amount of stimulation is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects this device to the electrodes in your brain
• These electrodes produce electrical impulses that
  a) Regulate abnormal impulses
  b) Affect certain cells and chemicals within the brain, but specific therapeutic mechanisms still unclear (lead to brain release of ATP -> build up of adenosine -> activating adenosine receptors reduces tremors – helped to treat Parkinson’s ect.)

Question 12

What is deep brain stimulation approved to treat?

Answer 12

 Dystonia
 Essential tremor 
 Parkinson’s disease 
 OCD
 Epilepsy 
 Only if they can’t be controlled in other ways

Question 13

What is DBS being studies as a potential treatment for?

Answer 13

 Addiction 
 Chronic pain 
 Cluster headache 
 Dementia 
 Depression (major) 
 Huntington’s disease 
 Multiple sclerosis 
 Stroke recovery 
 Tourette syndrome 
 Traumatic brain injury

Question 14

What does a CT scan do?

Answer 14

combines a series of X-ray images taken from different angles and uses computer processing to create cross-sectional images

Question 15

What is a CT scan used to do?

Answer 15

• quickly examine people with internal injuries from accidents or trauma
• Pinpoint the location of a tumour, infection or blood clot
• Guide procedures such as surgery, biopsy and radiation therapy
• Detect and monitor diseases such as cancer
• Monitor treatment effectiveness

Question 16

What is a Position emission tomography (PET) scan and what is it useful for?

Answer 16

• A PET scan uses a radioactive drug (tracer) to show brain activity
• Useful in revealing or evaluating tumours and other brain disorders such as AD and seizures
• Can be combined with CT and MRI
• Tracer may be injected, swallowed or inhaled depending on which organ or tissue being studied. Tracer collects in areas of body with higher activity which often correspond to areas of disease.

Question 17

What is an MRI and what is it used for?

Answer 17

• MRI uses a magnetic field and radio waves to create detailed images of the brain
• MRI is the most frequently used imaging test of the brain and spinal cord
• It is used to diagnose: aneurysms, disorders of the eye and inner ear, MS, spinal cord injuries, stroke, tumours, brain injury from trauma

Question 18

What does a function MRI (fMRI) do and what is it used for?

Answer 18

• fMRI measures metabolic changes within the brain
• Can be used to examine brain anatomy in people being considered for brain surgery
• It can also be used to assess damage from head injury or from disorders such as AD

Question 19

What does gene therapy involve and what are the approaches to it?

Answer 19

• Gene therapy involves altering the genes inside your body’s cells to treat or stop disease, instead of using drugs or surgery
• Several approaches
   Replacing a mutated gene that causes disease with a healthy copy of the gene
   Inactivating or ‘knocking out’ a mutated gene that is functioning improperly
   Introducing a new gene into the body to help fight disease

Question 20

How can gene therapy be achieved and what are commonly used viral vectors?

Answer 20

 Ex vivo gene transfer (insertion of genetically modified cells)
 Direct in vivo injection of viral vectors into the target tissue (simple, efficient and requires less surgical intervention than Ex vivo
 Commonly used viral vectors:
 Retroviral and lentiviral (Lv)
 Adenovirus (AdV) and adeno-associated virus (AAV)
 Herpes simplex virus (HSV)

Question 21

How does direct in vivo injection of a viral vector work?

Answer 21

• New gene is inserted into vector
• Vector enters target cells
• New gene is delivered into nucleus
• New gene then transferred to mRNA

Question 22

In humans what does gene therapy make use of?

Answer 22

intraparenchymal administration: straight into the brain to bypass the blood-brain barrier

Question 23

What do stem cells provide and what are their unique properties?

Answer 23

• Stem cells provide new cells for the body as it grows, and replace specialised cells that are damaged or lost
• Unique properties
   Self-renewal (divide over and over again)
   Change into other types of cell

Question 24

What are the three main types of stem cell?

Answer 24

 Embryonic stem cells
 Adult stem cells (multipotent – can only change into some cells in the body)
 Induced pluripotent stem cells (scientists make these in the lab – they are pluripotent)

Question 25

What are neural stem cells and what have they been considered for?

Answer 25

- Neural stem cells are a self-renewing population that generates the neurons and glia of the developing brain - They can be isolated, proliferated, genetically manipulated and differentiated in vitro and reintroduced into a developing adult or pathologically altered CNS - Neural stem cells have been considered for use in cell replacement therapies in various neurodegenerative diseases (e.g. AD, PD)

Question 26

How has neural stem cell therapy been used with mice?

Answer 26

- Used to treat mice with hyposmia - Stem cells delivered intranasally engraft to produce olfactory neurons - New neurons project to the brain olfactory bulb - Sense of smell was recovered