THE CHALLENGE
Fast, small, dilute, and crowded
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Fast
A release event lasts about a millisecond, and clearance takes milliseconds to seconds
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Small
The cleft is tens of nanometers wide, and terminals are about a micrometer across
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Dilute
Baseline levels in the extracellular fluid are often in the nanomolar range
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Crowded
Many similar molecules are present at much higher levels
A sensor must be fast, tiny, sensitive, and selective at once.
TIME
Fast events, slower tools
Different methods follow changes at very different speeds, and the slower ones average over many events.
The method you choose sets the speed you can see.
TWO MODES
Tonic and phasic
Tonic
Slow background levels that drift over minutes
Phasic
Fast bursts lasting about a second or less, often tied to a stimulus or reward
Both matter
A good experiment may need to see both
Some methods see the baseline, others see the bursts.
SELECTIVITY
Look-alikes in the way
Ascorbic acid
Vitamin C is present in the extracellular fluid at hundreds of micromolar, far above dopamine, and can also be oxidized at an electrode
Metabolites
Breakdown products such as DOPAC are chemically similar
Close cousins
Dopamine, norepinephrine, and serotonin respond at similar voltages
A sensor has to pick one molecule out of a crowd.
THREE TOOLBOXES
How the rest of this course measures
Sample it
Collect fluid and analyze it, as in microdialysis
Oxidize it
Detect the current when it reacts at an electrode, as in voltammetry
Light or charge
Use fluorescent proteins or transistors that respond to binding
Each toolbox trades speed, selectivity, and convenience.
UNIT 14 STUDY COMPLETE
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Ready for the Fab Challenge?
You've seen why neurotransmitters are hard to measure and what a good sensor needs.