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Transcript
An Introduction to Neurotransmission
William Wisden
Dept of Clinical Neurobiology
INF 364
[email protected]
Fundamental Neuroscience - second edition
Squire, Bloom, McConnell, Roberts, Spitzer, Zigmond
Academic Press, 2003
http://www.indstate.edu/thcme/mwking/home.html
http://www.indstate.edu/thcme/mwking/nerves.html
http://faculty.washington.edu/chudler/neurok.html
http://faculty.washington.edu/chudler/chnt1.html
Explore the Brain and Spinal Cord
The Neuron
A neuron
The action potential
Hodgkin & Huxley, 1939
Rate of action potential firing is information
The dendrite
Differences between axons and dendrites
Axons
Dendrites
Take information away from the cell body
Bring information to the cell body
Smooth Surface
Rough Surface (dendritic spines)
Generally only 1 axon per cell
Usually many dendrites per cell
No ribosomes
Have ribosomes
Can have myelin
No myelin insulation
Branch further from the cell body
Branch near the cell body
Dendrites constitute a kind of neural
microchip for complex computations
Rate of action potential firing is information
Frequency code of impulses within the axons
Place/topological code depending on which axons are active
Chemical synapse
Axon-dendrite
Axo-axonic
Axon-soma
Passing information between neurons
Gap junctions -electrical transmission
fast
both directions
Chemical transmission
slower - unidirectional
integrative
amplifies and regenerates the signal
The synapse
IN
OUT
Calcium entry is excitatory
Calcium is a second messenger which binds to target proteins
e.g. Calmodulin
Electrical Trigger for Neurotransmission
Ca2+
Action potential
Axon Terminal
Neurotransmitter Mobilization and Release
Diffusion of Neurotransmitters Across the Synaptic Cleft
Spine
Dendrite
Action potential
Depolarization
Ca2+
Electrical properties
How is the action potential generated?
http://faculty.washington.edu/chudler/ap.html
OUT
EXCITATORY +
IN
INHIBITORY -
INHIBITORY -
Look at the animation!
http://faculty.washington.edu/chudler/ap.html
Neurotransmitters
Excitatory
Excitatory
Inhibitory
Simple transmitters: g-aminobutyric acid (GABA)
glutamic acid (glutamate)
acetylcholine (Ach)
OUT
Cl-
Na+
Na+
Cl-
Na+
Na+
GABAA receptor
Inhibition
IN
Glutamate/AMPA
receptor
Acetylcholine
receptor
Excitation
Neurons and glial cells
The process of chemical neurotransmission can be
divided into five steps
1. Synthesis of the neurotransmitter in the presynaptic neuron
2. Storage of the neurotransmitter and/or its precursor in the
presynaptic nerve terminal
3. Release of the neurotransmitter into the synaptic cleft
4. Binding and recognition of the neurotransmitter by target receptors
5. Termination of the action of the released transmitter
Life cycle of a neurotransmitter
An excitatory (glutamatergic)
synapse
A synapse using g-aminobutyric acid (GABA)
A synapse that uses acetylcholine (ACh)
Simple circuits
Feed-forward inhibition
Negative feedback
Feedback inhibition
Neocortex
Interneuron - uses GABA
Pyramidal neuron
- uses glutamate
Ionotropic and metabotropic receptors
Fast
Slow
Ion flow in/out
Second messenger cascades
milliseconds
seconds
Ionotropic
Metabotropic
OUT
Cl-
Na+
Cl-
Na+
GABAA receptor
Inhibition
IN
Glutamate/AMPA
receptor
Excitation
Neuromodulators
Slow synaptic transmission