Synaptic transmission Flashcards
what structure is considered the ‘trigger zone’ that must reach threshold potential to achieve action potential?
the axon hillock
what are the two main inhibitory neurotransmitters
GABA and glycine
how is GABA synthesised
by removal of the carboxyl group from glutamate using glutamate decarboxylase
how many neurons and synapses are in the human brain
86 billion neurons and 100 trillion synapses
what is the main excitatory neurotransmitter in the central nervous system
glutamate
transcriptional regulation of what gene causes GABA synthesis
GAD1
what type of synapse is primarily associated with excitatory neurons
axo- dendritic synapse
how do excitatory and inhibitory synapses look different (molecular distinctions)
excitatory synapses - often asymmetric (due to thick specialisation of organiser proteins and cytoskeleton), more obvious accumulation of NT vesicles near the active zone release site
inhibitory synapses - are symmetric (thin specialisation of organiser proteins and cytoskeleton)
what ion flux during excitatory transmission
sodium and calcium
what ion s flux during inhibitory transmission
chlorine
what tools can be used to investigate DNA molecular neuroscience
promoter studies, identifying mouse mutants, disease forming mutations in humans
what tools can be used to investigate RNA molecular neuroscience
cDNAs, PCR and in-situ hybridization Gene profiling (e.g. microarrays, RNAseq).
what tools can be used to investigate protein molecular neuroscience
Antibody staining (western blotting or immunocytochemistry).
what molecular component causes variation in neuronal morphology
cytoskeleton - actin filaments, intermediate filaments, microtubules
where is the actin cytoskeleton often associated
in a cortical network enriched in terminal regions
where are the microtubules in neurons and how are they orientated
Microtubules orientated unidirectionally in the axon compartment but bi-directionally in the dendrite
what regulatory proteins are associated with microtubules
Tau and MAP2
whats the main function on microtubules in neurons
makes tracks for transport
how do microtubules aid transport of things inside neurons
kinesin (+end directed motor protein) binds one end to cargo the other to the microtubule, and walks (from soma) along the microtubule by hydrolysing ATP
what is the main orientation of inhibitory synapses
axo-somatic synapes
what is the common inhibitory NT vesicle transporter protein
Inhibitory amino acid vesicle transporter IAAT
what is the structure of voltage-gated sodium channels
one protein sequence that contains 4 domains each of which has a voltage sensor and 1/4 of the pore. each domain is made up of six alpha-helical transmembrane segments + reentrant loop (between S5 & S6)
what is the structure of voltage-gated potassium ion channels
made up of one protein sequence making up one domain of 6 alpha helical transmembrane loops. has a voltage sensor in the form of +ve K amino acids in the 4th segment. the reentrant loop between S5 & S6 makes up the pore
what senses voltage in voltage gated sodium and potassium ion channels
+ve amino acids K and R in the fourth transmembrane segment of each domain
what makes up the pore of voltage gated ion channels
the reentrant loop between the 5th and 6th transmebrane segments
what are the thresholds for activation and inactivation of voltage-gated sodium ion channels
for activation about -50 mV
for inactivation about 0 mv
what are the thresholds for activation and inactivation of voltage-gated potassium ion channels
activation about 0mV
inactivation about +50mV
what are the two ways of bridging the synaptic gap
electrical synapse and chemical synapse
what is the structure of electrical synapses
pre and postsynaptic membranes are in close proximity so gap junctions can form (6 subunit hemi dimers on each membrane join) for continual access
what two ways can you turn off a chemical synaptic signal
reuptake and diffusion away
enzymatic degradation in the case of acetylcholine
what does excitatory stimulation cause in the post synaptic cell
depolarisation
what does inhibitory stimulation cause in the post synaptic cell
hyperpolarisation
where is the major inhibitory input on the neuron
onto the soma
what is synaptotagmin and its role in synaptic transmission
a protein that binds calcium and changes its conformation to allow storage NT vesicles to see the calcium signal and collaborate with SNARE proteins to drive fusion
what are SNARE proteins and what is their role in synaptic transmission
Proteins on both NT vesicle and plasma membranes (with complementary domains) that come together to allow fusion and release of neurotransmitters into the synaptic cleft. (trigger by synaptotagmin)
what is the brief structure of glutamate receptors on the post synaptic membrane
four subunits with glutamate binding sites on the outside allowing cation flux
what organising protein is associated with excitatory synapses
PSD-95
what organising protein is associated with inhibitory post synaptic cells
gephrin
what is the brief structure of glycine receptors
five subunits make the ion channel with glycine binding on the outside allowing anion flux
what do organising proteins like PSD-95 and gephrin do to help synaptic segregation
selectively recruit tags (neurexins and neuroligins) that allow organising of synapses
what molecules are tags for pre synaptic neurons
neurexins
what molecules tag post synaptic neurons
neuroligins
which neuroligins tag inhibitory neurons and which tag excitatory ones
glutaminergic = neuroligins 1, 3 and 4 glycinergic = neuroligin 2
what is temporal summation
successive synaptic inputs before the neuron has time to recover can sum together to produce a greater overall effect
what is spatial summation
multiple synaptic inputs to different parts of the neuron can sum together produce=ing a greater overall effect
how is action potential intensity coded
by number of action potentials - AP frequency roughly proportional to the log of stimulus intensity up to a maximum
how is action potential modality coded
by which axon is activated
what is synaptic plasticity
activity-dependent changes to synaptic strength
which structure is more sensitive to long term potentiation
hippocampus
which structure shows long term depression but not much long term potentiation
cerebellum
what is long term depression of neurons
an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus (low frequency -> smaller response)
what is long term potentiation of neurons
a process by which synaptic connections between neurons become stronger with frequent activation (high frequency -> larger response)
what is metaplasticity
Metaplasticity refers to neural changes that are induced by activity at one point in time and that persist and affect subsequently induced LTP or LTD
how is metaplasticity different from synaptic plasticity
The ‘meta’ part of the term reflects the higher-order nature of the plasticity — that is, the plasticity of synaptic plasticity.
Essentially, metaplasticity entails a change in the physiological or biochemical state of neurons or synapses that alters their ability to generate synaptic plasticity
what is the chemistry of glutamate clearance
In astrocytes glutamate is converted into glutamine by glutamine synthetase (GS), released into the extracellular space, taken up by neurons and converted back into glutamate by phosphate activated glutaminase (GA).
what are the main target receptors for glutamate
Kainate receptors, metabotropic glutamate receptors (mGluRs), and especially NMDA receptors
