• discrete structural
entity
• functionally discrete Action
in space and time potential
Ca2+ Ca2+
Enzyme or
fast re-
uptake
Synaptic
Ligand-gated
cleft
receptor
Na+
NEUROMODULATION IN THE CNS
“setting” the activity level of neural pathways
Behaviour
• arousal – eg. sleep, appetite, locomotory
activity; raised/lowered thresholds
• learning and memory – alterations in the
effectiveness of specific transmission
pathways
“Classical” Synaptic Transmission
•Fast - for rapid signal transmission
e.g. ACh on
•Short-lived (msec) skeletal muscle -
excitation
•Ligand-gated (ionotropic) ion channels
Local Neuromodulation
•Slower
e.g. ACh on
•Longer-lived (sec) cardiac muscle –
slows heart rate
•Metabotropic receptors
B e.g.Serotonin 5HT
receptor (cAMP)
enzyme Receptor modulation
Protein
Second messenger cascade phosphorylation →
other cell processes
Second messenger pathways
G-Protein
Noradrenaline or cAMP
Noradrenaline → cAMP →
closes K+ channels in
postsynaptic membrane
mV
ms
post
Glutamate (ionotropic
via Ca2+ channels) pre
K+
An example of
‘postsynaptic
neuromodulation’
Presynaptic inhibition and facilitation
Selective regulation of synaptic efficacy
Change in
effectiveness/efficacy
of synapse
Neurotransmitter
Neuromodulator
Presynaptic Inhibition
GABA reduces
synaptic
transmission at a
specific synapse
Presynaptic Facilitation
An example of short/long term neuromodulation –
“presynaptic facilitation”
Increased neurotransmitter release from Aplysia sensory neurons
- underlies associative learning
5-HT
Voltage-gated
K channels