Molecular Neuroscience Flashcards
Why is the brain considered a non-vital organ?
The body can live even if brain-dead
What are promoter studies?
Looking at DNA promotor sequences and gene expression
Why is it useful to identify mouse mutants?
Changes in DNA can change behaviour
What is studied in cDNAs, PCR and in-situ hybridisation?
Cloning genes, gene expression levels around tissues, molecule positioning
What is involved in gene profiling?
Microassays, RNAseq, relative expression of genes, regulation by activity
What is studied in antibody staining (Western blotting / immunohistochemistry)?
Function generated by protein, regulation of synthesis, oligomerisation
What is the major excitatory neurotransmitter in the brain?
Glutamate
What is the major inhibitory neurotransmitter in the brain?
GABA
What does glutamic acid decarboxylase (GAD) do?
Turns glutamate into GABA
Where are GAD genes selectively expressed?
GABA neurones
What feature of processes remins unchanged?
Polarity
What features of processes are very dynamic?
Shape and length
What are the cytoskeletal elements of processes?
Microtubules, actin filaments and intermediate fibres
What are F-actin filaments composed of?
G-actin monomers
What is the microtubule orientation in axons?
(-) Cell body, (+) pre-synaptic terminal
What is the microtubule orientation in dendrites?
Can face either way
What is kinesin?
Motor protein for protein transport
How was kinesin discovered?
Reproduced giant squid axon cytoplasm with beads
What is the molecular weight of kinesin?
120kD
How does kinesin move proteins?
Binds to microtubules and cargo, walks along using ATP activity
What are the intracellular and extracellular concentrations of Na+?
Intracellular 10mM, extracellular 142mM
What are the intracellular and extracellular concentrations of K+?
Intracellular 140mM, extracellular 4mM
What are the intracellular and extracellular concentrations of Cl-?
Intracellular 4mM, extracellular 130mM
What are the intracellular and extracellular concentrations of Ca(2-)?
Intracellular 100mM, extracellular 2mM
What does Na/K ATPase do?
Pumps 3Na+ out and 2K+ in
What property of neurones allows intercellular communcation?
Process polarity
What net movement of ions excites the neuronal membrane?
Positive ions in
What net movement of ions inhibits excitation of the neuronal membrane?
Negative ions in or positive ions out
What is the mechanical linkage of neurones?
Gap junction channels forming electrical synapses
What are the activation and inactivation thresholds for Na+ channels?
Activation 50mV, inactivation 0mV
What are the activation and inactivation thresholds for K+ channels?
Activation 0mV, inactivation 50mV
What is the general structure of a Na+ channel?
Homo-tetramer
What is the general structure of a K+ channel?
Hetero-tetramer
What occurs in an electrical synapse transmission?
Signal passed directly between cells using Na+ and K+ channels
Which synaptic receptors have intrinsic ion channel activity?
Selective receptors on post-synaptic membrane
What are the two ways to turn a chemical signal off?
Diffusion of neurotransmitter, reuptake into pre-synaptic terminal (uptake 1)
What causes Ca(2+) to enter the presynaptic nerve terminal?
Neurone stimulation
What does synaptotagmin do?
Recognises Ca(2+) and changes conformation to facilitate SNARE
What do SNARE protein do?
Promote fusion of synaptic vesicles with the membrane
Which ion mediates neurotransmitter release?
Ca(2+)
What are the two types of SNARE proteins?
Vesicle and membrane SNAREs which complex together
What does a positive postsynaptic signal cause?
Membrane depolarisation, excitation
What does a negative postsynaptic signal cause?
Membrane hyperpolarisation, inhibition
In the brain, where do major excitatory neurones synapse?
Dendrite (axo-dendritic synapse)
Which neurotransmitter is commonly released into axo-dendritic synapses in the brain?
Glutamate
In the brain, where do major inhibitory neurones synapse?
Cell body (axo-somatic synapse)
Which neurotransmitters are commonly released into axo-somatic synapses in the brain?
GABA and glycine
Which transporter releases the neurotransmitter at glutamatergic synpases?
Vesicle glutamate transporter (VGT)
Which transporter releases the neurotransmitter at GABA/glycine synapses?
Inhibitor amino acid vesicle transporter (IAAT)
What is the general structure of the glutamate receptor?
Cation channel tetramer
What is caused by activation of glutamate receptors?
Flux of Na+ and Ca(2+)
What is bound by glutamate receptors intracellularly?
PSD-95
What is the general structure of the glycine receptor?
Anion channel pentamer
What is caused by the activation of glycine receptors?
Flux of Cl-
What is bound by glycine receptors intracellularly?
Gephyrin
Where in the brain are thick specialisation proteins and cytoskeleton found?
Post-glutamatergic-synaptic cell
Where in the brain are thin specialisation proteins and cytoskeleton found?
Post-glycinergic-synaptic cell
What is the role of multi-domain molecules in molecule organisation?
Assist with segregation
What is the role of neurexins?
Presynaptic tagging
What is the role of neuroligin 1?
Glutamatergic postsynaptic tagging
What is the role of neuroligin 2?
Glycinergic postsynaptic tagging
What are the drug targets for glutamate receptors?
Activators act against cognitive decline, inhibitors act against over-excitation
What does PSD-95 do?
Organise excitation of neurones in the brain
What is hyperekplexia?
Increased startle response
What causes hyperekplexia?
Mutation reducing function of glycine receptors
What does gephyrin do?
Organise inhibition of neurones in the brain
What causes stiffness syndrome?
Auto-antibodies against gephyrin
What can be used to treat stiffness syndrome?
Intravenous introduction of IgG
How are neurexins and neuroligins linked to autism?
Mutations affect synapse development
