Lectures Flashcards
What features do synaptic number and strength underlie?
Processing sensory information
Motor circuits
Memory formation
Synaptic plasticity
According to what features can neurones be grouped?
Shape Electrical activity Gene expression profile Neurotransmitter Connectivity
Cells that wrap myelin sheath around neuron
Oligodendrocytes
Cells that act like the immune cells of the brain
Microglia
Maintain neural energy balance, buffer and provide nutrition
Astrocytes
Line ventricles of the brain and secrete CSF
Epindymal cells
Glue. Provide tropic support, modulate electrical output of neurones and protect them from external factors
Glia
What are the components of a tripartite synapse?
Presynaptic terminal, post synaptic spine and astrocyte process (glia)
What is the role of astrocytes in the tripartite synapse?
Neurotransmitter recycling, release of gliotransmitters eg d serine or ATP and to ensheath
Which cells carry out synaptic pruning and how?
Microglia
They remodel dendritic spines, changing the cell input
What process to robo and slit control?
Midline crossing
What ligand binds robo?
Slit ligand (chemorepellant)
What direction do axons expressing high robo grow and why?
Grow longitudinally as there repelled by slit
Which direction do axons expressing low robo grow and why?
They cross the midline as they are attracted to it
What happens after axons cross the midline?
Robo is upregulated and they continue to grow longitudinally on the contralateral side
What morphagen allows development of the dorso ventral axis?
Sonic hedgehog
What structure secretes sonic hedgehog?
The notochord
What does a reduced production of Shh by the notochord lead to?
More dorsal interneurons form further from the notochord
What determines the formation of the anterio posterior axis?
Hox gene expression
What is the brainstem said to be divided into (physical segmentation)?
Rhombomeres
What controls peripheral axon projection?
Neurophilin receptors and semaphorin ligands
What is repelled by semaphorin ligands?
Dorsal root ganglia
What binds NRP1?
SEMA 3A
What binds NRP2?
SEMA 3F
What ligand binds EPh receptors?
Ephrin
What two things are expressed in complementary gradients in the retina and tectum, showing complimentary gradients of guidance cues?
EPh receptors and ephrin ligands
Where are axons from the temporal retina directed?
Anterior tectum
Where are axons from the nasal retina directed?
Posterior tectum
What is the complementary gradients of guidance cues between the retina and tectum an example of?
Topographic mapping within the nervous system
What are the advantages of phase contrast microscopy?
Only requires low illumination
No labelling required
Cheap
What are the disadvantages of phase contrast microscopy?
Can’t automate image analysis
Can only distinguish between structures with high contrast
What are the advantages of fluorescent wide field microscopy?
Increased discrimination and temporal resolution when compared to phase contrast
What are the disadvantages of wide field fluorescent microscopy?
High illumination required.
Limited depth of information
What are the advantages of confocal fluorescent microscopy?
3D image
Even higher discrimination than phase contrast and wide field fluorescent microscopy
Allows image analysis
Can be done in living cell
What are the disadvantages of confocal fluorescent microscopy?
Expensive
High illumination and long acquisition time required
How can mouse models be used in neuroscience?
Their cortex forms layers like ours, meaning that higher brain function can be studied
How can frogs be used as animal models in neuroscience?
Can be used to study robo/ slit guidance cues.
This is a good model to show the brain stem and early projections
How can flies be used as animal models in neuroscience?
Drosophila have many common neurotransmitters with humans, and can be used to study how the nervous system is wired up and modelling of human diseases.
How can chick embryos be used as animal models in neuroscience?
You don’t require a home office license to work with chick embryos, as it is considered ethical.
Minimal husbandry costs and good for modelling early neuronal development, as this is highly conserved.
Also good for studying visual system for the same reason, and that they have large eyes
What is an agonist?
A drug that binds the receptor keeping it in the R* state/ has a higher affinity for R* state
What is an inverse agonist?
Has a higher affinity for the R state than the R* state
What is an antagonist?
Doesn’t directly have higher/ lower affinity for the R/R* state, but binds to the receptor in competition with the agonist/ inverse agonist, reducing its effect
What type of drug allows full receptor saturation?
Full agonist
What type of drug binds to the receptor but won’t cause full saturation?
Partial agonist
What type of drug competes with the agonist to prevent binding but has no downstream effect?
Neutral antagonist
What type of drug has a higher affinity for the R state, reducing the number of receptors in the active fraction?
Inverse agonist
What type of binds do irreversible antagonists form?
Covalent
By what mechanism does an irreversible antagonist prevent agonist binding?
Causes a conformational change. It is capable of lowering receptor efficacy, as the antagonist remains bound until the receptor is internalised and recycled
How well the drug binds the receptor
Affinity
How well the drug, once bound to the receptor elicits a response
Efficacy
A measure of the amount of drug required to elicit a response of a give intensity
Potency
What is an allosteric modulator?
Drug that binds alternative (allosteric) site & alters signalling
What is the role of a positive allosteric modulator?
Binds to the allosteric site and enhances signalling by increasing binding or efficacy of the orthosteric agonist
What is the role of a negative allosteric modulator?
Binds to the allosteric site reducing signalling by decreasing agonist binding or efficacy at the orthosteric site
What is the role of a neutral allosteric modulator?
Bids the allosteric site but leads to unaltered signalling
How do allosteric modulators modulate drug efficacy?
They can alter conformation of the receptor
How do allosteric modulators alter the drug affinity for the receptor?
They make binding more or less difficult
Define a neurotransmitter
Biochemical that mediates fast acting direct communication between 2 neurones - pre and post synaptic
Define neuromodulator
Biochemical that modulates activity of neurones and neuronal networks by changing the ability of neurones to respond to neurotransmitters.
Can act at sites remote from where they’re synthesised
True or false some neurotransmitters can act as neuromodulators
True
Name some examples of amino acid neurotransmitters
Glutamate (+)
Aspartate (+)
GABA (-)
Glycine (+/-)
What type of receptors are NMDA, AMPA and kainate receptors?
Ionotropic glutamate receptors
GABAa, nicotinic AChR and 5HT3 are examples of what type of receptor?
Ligand gated ion channels (ionotropic)
Which two receptors are allosterically modulated by an Mg2+ block?
NMDA and GABAa
How are group 1, 2 and 3 GPCRs coupled?
Group 1 = Gq
Group 2 = Gi/Go
Group 3 = Gi/Go
What are the members of the group 1 GPCRS
mGlu1 and mGlu5
What are the members of Group 2 GPCRS
mGlu2 and mGlu3
What are the members of group 3 GPCRS
mGlu4 and mGlu6-8
What is the subunit composition of NMDA, AMPA and Kainate receptors respectively?
Tetramers of GluN 1-3
Tetramers of GluA 1-4
Tetramers of GluK 1-5
Are NMDA receptors located pre or post synaptically?
Post synaptically
Are AMPA receptors located pre or post synaptically?
Presynaptically
ARE Kainate receptors located pre or post synaptically?
Pre and post synaptically
What is an example of a kinase linked receptor?
Cytokine receptors
What is an example of nuclear (hormone) receptors?
Glucocorticoid receptor
Oestrogen receptor
What are the three ways reduced signalling can occur, leading to receptor desensitisation?
Uncoupling of agonist binding from signalling
Internalisation of receptor
Reduction of receptor expression, due to reduced synthesis or degradation
Define tachyphylaxis
Acute, sudden decrease in response to drug after administration
Define tolerance
Decrease response to drug after chronic use
Define addiction
Behavioural manifestation of tolerance