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BIO 132
Neurophysiology
Lecture 34
Diffuse Modulatory
System
Lecture Goals:
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Understanding the advantage of having a diffuse
modulatory system
Understanding the differences between the four
diffuse modulatory systems
Diffuse Modulatory Systems
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We will discuss four different diffuse
modulatory systems in the brain:
Noradrenergic
 Cholinergic
 Dopaminergic
 Serotonergic
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Each has a different function but they all have
certain common principles.
Commonalities of the Diffuse Modulatory Systems
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Each system has a small core of neurons (only a few
thousand)
Most of the cores are found in the central core of the
brain and brain stem
Each neuron from the core can influence more than
100,000 postsynaptic neurons spread all over the brain
The synapses are not terminal but rather run along
axons (called boutons en passant)
Each system only modulates the actions of other
neurons and does not turn them on or off.
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Like adjusting the volume on a radio instead of the power
Boutons en Passant
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Boutons en passant is a French term meaning
“buttons in passing”.
An axon terminal (“terminal bouton”) is what
we normally think of as having the voltagegated calcium channels and secretory vesicles
but some neurons can have these areas strung
along their axons like a string of pearls.
The synapses are not terminal but rather run
along axons (called boutons en passant)
Boutons en Passant
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Neurons from the core meander through the brain, and
when activated, release neurotransmitter from
thousands of sites along the axon.
Any neuron in close proximity is affected.
Cell body/dendrites
Boutons en passants
Axon terminal
(terminal bouton)
The Noradrenergic System
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Neurons from this system release norepinephrine (NE)
The core of this system is called the locus coeruleus
(meaning “blue spot”) and is located in the pons.
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Each locus coeruleus (there is one on each side) contains
~12,000 neurons.
Destination: Nearly everywhere in
brain (Cerebral cortex, cerebellum,
thalamus, hypothalamus, spinal
cord, etc)
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A single neuron from this system can
make connections with over 250,000
neurons.
Noradrenergic System
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Stimulus: Novel, unexpected, non-painful stimuli
(has low activity while sitting quietly)
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Effect: Thought to make neuronal signalling and
processing faster and more efficient (increases
the signal to noise ratio)
The Serotonergic System
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Neurons from this system release serotonin (5-HT)
This system cores are located in the nine Raphe nuclei
(located in the brain stem).
Destination: Everywhere in the
central nervous system
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Superior Raphe project up to the
cortex
Inferior Raphe project down the
spinal cord
Serotonergic System
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Stimulus: Most active during active awake states
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Effects:
Superior Raphe seem to be involved in regulating
sleep/wake states. They have also been implicated in
altering mood and certain emotional behaviors.
 Inferior Raphe inhibit nocioception in the spinal
cord.
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The Dopaminergic System
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Neurons from this system release dopamine (DA)
This system has two cores: Substantia nigra (SN) and
the Ventral tegmental area (VTA).
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Destinations:
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SN projects to the Basal ganglia
VTA projects to the Frontal cortex
Dopaminergic System
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Effects:
The Substantia nigra seems to facilitate the initiation
of motor responses by environmental stimuli.
 The VTA seems to be involved in “rewarding”
behavior. Note this is not the same as feeling
pleasure. The VTA pairs behavior or sensation with
a feeling of satisfaction.
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The Cholinergic System
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Neurons from this system release Acytelcholine (ACh)
This system has three cores: Medial septal nucleus
(MSN), the Basal nucleus of Meynert (BNM), and the
Pontomesencephalotegemtal complex (PC).
Destinations:
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MSN projects to the Hippocampus
BNM projects to the cerebral cortex
PC projects to the thalamus
Cholinergic System
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Effects:
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The effects of the MSN and BNM are unclear but
there is evidence that they are involved in the laying
down of memories
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Damaged to these areas linked to Alzheimer’s disease
The PC seems to be involved in sensory filtering by
the thalamus.
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Effects of Drugs on Diffuse Modulatory
Systems
Hallucinogens (e.g. LSD)
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Thought to stimulate the Serotonergic system.
Stimulants (e.g. cocaine, amphetamines):
Feelings of heightened awareness.
 Evidence shows these drugs inhibit the reuptake of
NE and DA, causing prolonged exposure of
receptors to these neurotransmitters.
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In the case of DA, this can reward drug use behavior.
Effects of Drugs on Diffuse Modulatory
Systems