REVISION Flashcards
Engrailed gene
Segmentation of epidermis in drosophila - homologous gene in other animals affects cerebellar and limb development in other animals
Pax 6/eyeless
Eye-ness and limb-ness
PCA - principal components analysis
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
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?
Macro (whole brain connectivity)
Meso (connectivity between regions of neurons)
Micro (synaptic connectivity)
Numerosity interacts with language and spatial representation to make
Maths
Numerosity interacts with sensitivity to frequency (prosody) in language to make
Language of sound in terms of spatial and temporal freq relations (music)
Cellular automata (CA)
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.
Two dimensions of pain
- Sensory-discriminative: location, intensity, duration of the pain
- Motivational-affective: unpleasant feelings (e.g. fear) associated with pain
How does NGF act to increase peripheral sensitization?
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.
3 Types of Pain
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
3 Types of dorsal horn neurons
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
What does IL1Beta released by vascular endothelial cells do?
Induce COX-2 on neurons
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?
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)
Spinothalamict tract aka anterolateral system aka ventrolateral system - what info does ant and lat pathway convey? When does pathway decussate?
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
Intensity theory/Convergence vs Specificity theory
Strong activation of unspecialised neurons
Specialised LTh and HTh neurons
Maladaptive pain - 2 classes
1) Neuropathic - lesion
2) Dysfunctional - idiopathic, no lesion- e.g. CGRP
Erythromelalgia - what is it? Treatment? What mutation causes it?
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)
Endogenous opioids have a specific a.acid sequence they begin with - what is it?
Tyr-Gly-Gly-Phe
Does A-beta terminate in the superficial or deep dorsal horn?
Deep
*Their presynaptic terminals are among the most complex in the CNS
Drug treatment
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
Genetic mutations in the __ signalling system, decreasing amount of it increase/decrease likelihood of anxiety
5-HT, increase
Low 5-HT expression increases vulnerability to adverse experiences but also? How did mice studies show that 5HTT polymorphism is a vulnerability mutation?
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
Can we inherit our parents environment?
Grandparenqts experience can impact on your health via germlines by epigenetic modifiers MAINLY FEMALES NOT MALES
After analysing sperm of stressed fathers (which lead to anxious children), what differences was found that might be passed down from father to children?
MicroRNA - Small, sticky, stops translation
Abstinence vs relapse circuit
Relapse circuit
-Prelimbic cortex to NAc core
Abstinence/extinction circuit
-Infralimbic cortex to Nac shell
Glu levels in extracellular space are regulated by transporters in astrocyte called?
GLT1 aka EAAT2 takes Glu into cell
AND
Xc- is putting Glu into extracellular space
In relapse vs drug withdrawal condition, what is shown at the Glu synapse between prelimbic cortex and nucleus accumbens?
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
How can we reverse the altered glutamate homeostasis in addiction?
N-Acetylcysteine mechanism - also makes rats less prone to relapse
In social drinkers, what brain areas are activated? What about heavy drinkers?
VS and PFC
Heavy drinkers - shifts from VS to Dorsal Striatum activation (much more involved in habits)
More than a ventral to dorsal shift in the striatum but within DS, there is a ____ to ____ shift as drug taking becomes habitual
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
What drug can rescue adolescent deficit in cue extinction?
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
