Transmission in the CNS
WHY CONNECTIVITY MATTERS
Cognitive ability is not determined by neuron number
Human brain power arises from:
o connectivity
o circuit organisation
o dynamic communication between neurons
Brain function emerges from circuits, not individual neurons
o movement
o cognition
o emotion
o psychiatric and neurological disease
Neuropharmacology aims to:
o use drugs as tools to probe circuits
o use drugs as treatments to correct dysfunctional signalling
LEVELS OF ANALYSIS IN NEUROPHARMACOLOGY
Neuropharmacology spans multiple levels:
Molecular
o receptors, ion channels, transporters, enzymes
Cellular
o synaptic integration, membrane excitability
Circuit
o patterned neuronal activity
Whole-system
o behaviour, cognition, disease states
Drug effects emerge at the system level, even if the target is molecular.
THE MYTH OF 1:1 NEUROTRANSMISSION
Classical model:
one neuron → one neuron
one synapse
one neurotransmitter
one postsynaptic effect
Reality:
Neurons receive thousands of synaptic inputs
Neurons integrate multiple simultaneous signals into one output
Signalling is dynamic, not hard-wired - is modulated
Feedback exists - retrograde signals
Context (location, timing, neighbouring receptors) all influence
, Neurons compute, they don’t relay.
STRUCTURAL REALITY OF THE BRAIN
Brain tissue is densely packed
o no empty “white space”
Electron microscopy shows:
o dendrites, axons, synapses tightly interwoven
Implications:
o neurotransmitters can diffuse
o neighbouring synapses can influence each other
o extrasynaptic signalling becomes possible
SYNAPTIC INPUT DIVERSITY
A single neuron receives:
o inputs from many neurons
o different neurotransmitters
Therefore, postsynaptic neurons express:
o multiple receptor types
Integration depends on:
o which inputs are active
o where they are located on the neuron
WHAT IS A NEUROTRANSMITTER?
Classical definition (historical):
synthesised in neuron
released at synapse
binds receptors
action terminated
Modern reality:
many signalling molecules do not fit neatly
disagreement led to term “neuromodulator”
o neurotransmitter = on/off
o neuromodulator = dimmer
Current consensus:
distinction is unhelpful
focus on function, not labels
most signalling molecules are now grouped as neurotransmitters
WHY CONNECTIVITY MATTERS
Cognitive ability is not determined by neuron number
Human brain power arises from:
o connectivity
o circuit organisation
o dynamic communication between neurons
Brain function emerges from circuits, not individual neurons
o movement
o cognition
o emotion
o psychiatric and neurological disease
Neuropharmacology aims to:
o use drugs as tools to probe circuits
o use drugs as treatments to correct dysfunctional signalling
LEVELS OF ANALYSIS IN NEUROPHARMACOLOGY
Neuropharmacology spans multiple levels:
Molecular
o receptors, ion channels, transporters, enzymes
Cellular
o synaptic integration, membrane excitability
Circuit
o patterned neuronal activity
Whole-system
o behaviour, cognition, disease states
Drug effects emerge at the system level, even if the target is molecular.
THE MYTH OF 1:1 NEUROTRANSMISSION
Classical model:
one neuron → one neuron
one synapse
one neurotransmitter
one postsynaptic effect
Reality:
Neurons receive thousands of synaptic inputs
Neurons integrate multiple simultaneous signals into one output
Signalling is dynamic, not hard-wired - is modulated
Feedback exists - retrograde signals
Context (location, timing, neighbouring receptors) all influence
, Neurons compute, they don’t relay.
STRUCTURAL REALITY OF THE BRAIN
Brain tissue is densely packed
o no empty “white space”
Electron microscopy shows:
o dendrites, axons, synapses tightly interwoven
Implications:
o neurotransmitters can diffuse
o neighbouring synapses can influence each other
o extrasynaptic signalling becomes possible
SYNAPTIC INPUT DIVERSITY
A single neuron receives:
o inputs from many neurons
o different neurotransmitters
Therefore, postsynaptic neurons express:
o multiple receptor types
Integration depends on:
o which inputs are active
o where they are located on the neuron
WHAT IS A NEUROTRANSMITTER?
Classical definition (historical):
synthesised in neuron
released at synapse
binds receptors
action terminated
Modern reality:
many signalling molecules do not fit neatly
disagreement led to term “neuromodulator”
o neurotransmitter = on/off
o neuromodulator = dimmer
Current consensus:
distinction is unhelpful
focus on function, not labels
most signalling molecules are now grouped as neurotransmitters
