Lectures Flashcards by Alice Crocker

What features do synaptic number and strength underlie?

Processing sensory information
Motor circuits
Memory formation
Synaptic plasticity

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According to what features can neurones be grouped?

Shape
Electrical activity 
Gene expression profile
Neurotransmitter 
Connectivity

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Cells that wrap myelin sheath around neuron

Oligodendrocytes

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Cells that act like the immune cells of the brain

Microglia

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Maintain neural energy balance, buffer and provide nutrition

Astrocytes

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Line ventricles of the brain and secrete CSF

Epindymal cells

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Glue. Provide tropic support, modulate electrical output of neurones and protect them from external factors

Glia

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What are the components of a tripartite synapse?

Presynaptic terminal, post synaptic spine and astrocyte process (glia)

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What is the role of astrocytes in the tripartite synapse?

Neurotransmitter recycling, release of gliotransmitters eg d serine or ATP and to ensheath

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Which cells carry out synaptic pruning and how?

Microglia

They remodel dendritic spines, changing the cell input

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What process to robo and slit control?

Midline crossing

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What ligand binds robo?

Slit ligand (chemorepellant)

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What direction do axons expressing high robo grow and why?

Grow longitudinally as there repelled by slit

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Which direction do axons expressing low robo grow and why?

They cross the midline as they are attracted to it

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What happens after axons cross the midline?

Robo is upregulated and they continue to grow longitudinally on the contralateral side

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What morphagen allows development of the dorso ventral axis?

Sonic hedgehog

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What structure secretes sonic hedgehog?

The notochord

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What does a reduced production of Shh by the notochord lead to?

More dorsal interneurons form further from the notochord

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What determines the formation of the anterio posterior axis?

Hox gene expression

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What is the brainstem said to be divided into (physical segmentation)?

Rhombomeres

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What controls peripheral axon projection?

Neurophilin receptors and semaphorin ligands

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What is repelled by semaphorin ligands?

Dorsal root ganglia

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What binds NRP1?

SEMA 3A

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What binds NRP2?

SEMA 3F

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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