REVISION

Question 1

Engrailed gene

Answer 1

Segmentation of epidermis in drosophila - homologous gene in other animals affects cerebellar and limb development in other animals

Question 2

Pax 6/eyeless

Answer 2

Eye-ness and limb-ness

Question 3

PCA - principal components analysis

Answer 3

Convert possible correlated variables to linear uncorrelated variables called principal components. Emphasizes variation and brings out strong patterns - makes data easy to explore and visualise

Question 4

Given that there might be 1-^15 connections in the human brain, we might need to look at bigger less detailed pictures of connectivity. Scales to consider?

Answer 4

Macro (whole brain connectivity)
Meso (connectivity between regions of neurons)
Micro (synaptic connectivity)

Question 5

Numerosity interacts with language and spatial representation to make

Answer 5

Maths

Question 6

Numerosity interacts with sensitivity to frequency (prosody) in language to make

Answer 6

Language of sound in terms of spatial and temporal freq relations (music)

Question 7

Cellular automata (CA)

Answer 7

Cells in a grid and their interactions. It uses simple rules to generate complex patterns. It is analogous to formal systems, whose axioms and rules of inference are very simple, yet vast bodies of mathematical theory can be derived from the repeated (recursive) activity of the system.

Question 8

Two dimensions of pain

Answer 8

• Sensory-discriminative: location, intensity, duration of the pain
• Motivational-affective: unpleasant feelings (e.g. fear) associated with pain

Question 9

How does NGF act to increase peripheral sensitization?

Answer 9

Increasing TTX resistant Na+ (NaV1.8) - this would increase excitability of the nerve ending = more ready to generate AP

By stimulating the synthesis of TRPV1, Bradykinin receptors and Na+ channels - these changes contribute to maintaining the reduced threshold of nociceptors.

Question 10

3 Types of Pain

Answer 10

1) Nociceptive pain - acute pain arising from threatened or actual damage to non-neural tissue
2) Inflammatory pain
3) Neuropathic pain - caused by lesion or disease of the somatosensory NS

Question 11

3 Types of dorsal horn neurons

Answer 11

1) Low threshold neurons
Respond only to innocuous stimulation e.g. light touch, pressure

2) Nociceptor specific (high threshold) neurons
Respond only to noxious stimuli, hyperalgesia

3) Wide dynamic range neurons
Responds to both noxious and innocuous stimuli
-Allodynia and hyperalgesia
-receive signals from multiple tissues including skin, viscera, muscles and joints

Question 12

What does IL1Beta released by vascular endothelial cells do?

Answer 12

Induce COX-2 on neurons

Question 13

WIND UP

a) What is wind-up generated by?
b) What does it require? (Not central sensitisation but contributes to it)
c) Effect on A-delta fibres?
d) Out of the 3 types of dorsal horn neurons - which does it affect? Is it LT or ST sensitization of dorsal horn neurons?

Answer 13

a) Repeated activation of C-fibre nociceptors leading to a progressive increase in perceived pain (e.g. doesn’t lower threshold but generates greater activity for the same stimulus)
b) It requires high freq input arriving at more than 1 impulse every 3 seconds
c) Response to A-delta fibre inputs remain unchanged
d) Characteristic of wide-dynamic range neurons (affects them more than nociceptive neurons). Short term sensitization (mins to hours)

Question 14

Spinothalamict tract aka anterolateral system aka ventrolateral system - what info does ant and lat pathway convey? When does pathway decussate?

Answer 14

Anterior pathway - info about firm pressure and crude touch (sense that someone has touched you but you can’t localise where)

Lateral pathway - conveys pain and temperature

Decussates at the level of the spinal cord - hence is a contralateral pathway

Question 15

Intensity theory/Convergence vs Specificity theory

Answer 15

Strong activation of unspecialised neurons

Specialised LTh and HTh neurons

Question 16

Maladaptive pain - 2 classes

Answer 16

1) Neuropathic - lesion

2) Dysfunctional - idiopathic, no lesion- e.g. CGRP

Question 17

Erythromelalgia - what is it? Treatment? What mutation causes it?

Answer 17

Mild warmth induces intense, burning pain in affected extremities, severe redness (erythema), and increased skin temperature that may be episodic or almost continuous in nature.

Treatment - using cooling to decrease pain exacerbated by warmth

Two gain of function mutations in Nav1.8 voltage gated Na channel gene - channels are open for longer (activity of channel amplified) and threshold lower (quicker activation)

Question 18

Endogenous opioids have a specific a.acid sequence they begin with - what is it?

Answer 18

Tyr-Gly-Gly-Phe

Question 19

Does A-beta terminate in the superficial or deep dorsal horn?

Answer 19

Deep

*Their presynaptic terminals are among the most complex in the CNS

Question 20

Drug treatment

Answer 20

Pharm treatment of acute pain:

• Mild to mod: NSAIDS (paracetamol and ibuprofan)
• Moderate to severe: Morphine

Pharm treatment of chronic pain (in itself, it is a dissociation between nociception and pain)

• Mild to mod: Gabapentin, Tramadol (has opioid and antidepressant actions)
• Mod to severe: Morphine and relatives

Question 21

Genetic mutations in the __ signalling system, decreasing amount of it increase/decrease likelihood of anxiety

Answer 21

5-HT, increase

Question 22

Low 5-HT expression increases vulnerability to adverse experiences but also? How did mice studies show that 5HTT polymorphism is a vulnerability mutation?

Answer 22

Enhances susceptibility to beneficial experiences

5HTT KO mice don’t go into open areas BUT 5HTT KO enriched environment mice do
*Mice can be vulnerable to anxiety but also vulnerable to enriching environment

Question 23

Can we inherit our parents environment?

Answer 23

Grandparenqts experience can impact on your health via germlines by epigenetic modifiers MAINLY FEMALES NOT MALES

Question 24

After analysing sperm of stressed fathers (which lead to anxious children), what differences was found that might be passed down from father to children?

Answer 24

MicroRNA - Small, sticky, stops translation

Question 25

Abstinence vs relapse circuit

Answer 25

Relapse circuit
-Prelimbic cortex to NAc core

Abstinence/extinction circuit
-Infralimbic cortex to Nac shell

Question 26

Glu levels in extracellular space are regulated by transporters in astrocyte called?

Answer 26

GLT1 aka EAAT2 takes Glu into cell
AND
Xc- is putting Glu into extracellular space

Question 27

In relapse vs drug withdrawal condition, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?

Answer 27

Swelling of synaptic spine, increased amount of Glu in extracellular space as EAAT2 and MGluR2/3 autoreceptors are impaired

BUT for drug withdrawl - increased amounts of AMPA R on post syaptic terminal

Question 28

How can we reverse the altered glutamate homeostasis in addiction?

Answer 28

N-Acetylcysteine mechanism - also makes rats less prone to relapse

Question 29

In social drinkers, what brain areas are activated? What about heavy drinkers?

Answer 29

VS and PFC

Heavy drinkers - shifts from VS to Dorsal Striatum activation (much more involved in habits)

Question 30

More than a ventral to dorsal shift in the striatum but within DS, there is a ____ to ____ shift as drug taking becomes habitual

Answer 30

Medial to lateral

• Medial is goal orientated so when rat is punished, it stops taking cocaine
• Lateral are habitually responding, becoming insensitive to punishment as behaviour is more automatic

Question 31

What drug can rescue adolescent deficit in cue extinction?

Answer 31

Quinpirole - DA D2R agonist in the Infralimbic cortex

Aripiprazole (partial agonist) can also be used

*D2 signalling in infralimbic cortex (extinction pathway) increases extinction learning -protecting rats from relapse