BIO 132BIO 132NeurophysiologyNeurophysiology

Lecture 34Lecture 34

Diffuse Modulatory Diffuse Modulatory SystemSystem

Lecture Goals:Lecture Goals:

Understanding the advantage of Understanding the advantage of having a diffuse modulatory systemhaving a diffuse modulatory system

Understanding the differences Understanding the differences between the four diffuse modulatory between the four diffuse modulatory systemssystems

We will discuss four different diffuse modulatory systems in the brain:We will discuss four different diffuse modulatory systems in the brain: NoradrenergicNoradrenergic CholinergicCholinergic DopaminergicDopaminergic SerotonergicSerotonergic

Each has a different function but they all have certain common principles.Each has a different function but they all have certain common principles.

Diffuse Modulatory Systems

Each system has a small core of neurons (only a Each system has a small core of neurons (only a few thousand)few thousand)

Most of the cores are found in the central core of Most of the cores are found in the central core of the brain and brain stemthe brain and brain stem

Each neuron from the core can influence more than Each neuron from the core can influence more than 100,000 postsynaptic neurons spread all over the 100,000 postsynaptic neurons spread all over the brainbrain

The synapses are not terminal but rather run along The synapses are not terminal but rather run along axons (called boutons en passant)axons (called boutons en passant)

Each system only modulates the actions of other Each system only modulates the actions of other neurons and does not turn them on or off.neurons and does not turn them on or off. Like adjusting the volume on a radio instead of the powerLike adjusting the volume on a radio instead of the power

Commonalities of the Diffuse Modulatory Systems

Boutons en passant is a French term Boutons en passant is a French term meaning “buttons in passing”.meaning “buttons in passing”.

An axon terminal (“terminal bouton”) is An axon terminal (“terminal bouton”) is what we normally think of as having the what we normally think of as having the voltage-gated calcium channels and voltage-gated calcium channels and secretory vesicles but some neurons can secretory vesicles but some neurons can have these areas strung along their axons have these areas strung along their axons like a string of pearls.like a string of pearls.

The synapses are not terminal but rather The synapses are not terminal but rather run along axons (called boutons en passant)run along axons (called boutons en passant)

Boutons en Passant

Neurons from the core meander through Neurons from the core meander through the brain, and when activated, release the brain, and when activated, release neurotransmitter from thousands of sites neurotransmitter from thousands of sites along the axon.along the axon.

Any neuron in close proximity is affected.Any neuron in close proximity is affected.

Boutons en Passant

Axon terminal(terminal bouton)

Boutons en passants

Cell body/dendrites

Neurons from this system release norepinephrine Neurons from this system release norepinephrine (NE)(NE)

The core of this system is called the locus coeruleus The core of this system is called the locus coeruleus (meaning “blue spot”) and is located in the pons.(meaning “blue spot”) and is located in the pons. Each locus coeruleus (there is one on each side) contains Each locus coeruleus (there is one on each side) contains

~12,000 neurons.~12,000 neurons.

The Noradrenergic System

Destination: Nearly Destination: Nearly everywhere in brain (Cerebral everywhere in brain (Cerebral cortex, cerebellum, thalamus, cortex, cerebellum, thalamus, hypothalamus, spinal cord, hypothalamus, spinal cord, etc)etc) A single neuron from this A single neuron from this

system can make connections system can make connections with over 250,000 neurons.with over 250,000 neurons.

Stimulus: Novel, unexpected, non-Stimulus: Novel, unexpected, non-painful stimuli (has low activity painful stimuli (has low activity while sitting quietly)while sitting quietly)

Effect: Thought to make neuronal Effect: Thought to make neuronal signalling and processing faster and signalling and processing faster and more efficient (increases the signal more efficient (increases the signal to noise ratio)to noise ratio)

Noradrenergic System

Neurons from this system release Neurons from this system release serotonin (5-HT)serotonin (5-HT)

This system cores are located in the nine This system cores are located in the nine Raphe nuclei (located in the brain stem).Raphe nuclei (located in the brain stem).

The Serotonergic System

Destination: Everywhere Destination: Everywhere in the central nervous in the central nervous systemsystem Superior Raphe project up Superior Raphe project up

to the cortexto the cortex Inferior Raphe project down Inferior Raphe project down

the spinal cordthe spinal cord

Stimulus: Most active during active Stimulus: Most active during active awake statesawake states

Effects:Effects: Superior Raphe seem to be involved in Superior Raphe seem to be involved in

regulating sleep/wake states. They have regulating sleep/wake states. They have also been implicated in altering mood also been implicated in altering mood and certain emotional behaviors.and certain emotional behaviors.

Inferior Raphe inhibit nocioception in the Inferior Raphe inhibit nocioception in the spinal cord.spinal cord.

Serotonergic System

Neurons from this system release dopamine (DA)Neurons from this system release dopamine (DA) This system has two cores: Substantia nigra (SN) and the This system has two cores: Substantia nigra (SN) and the

Ventral tegmental area (VTA).Ventral tegmental area (VTA).

Destinations:Destinations: SN projects to the Basal gangliaSN projects to the Basal ganglia VTA projects to the Frontal cortexVTA projects to the Frontal cortex

The Dopaminergic System

Effects:Effects: The Substantia nigra seems to facilitate The Substantia nigra seems to facilitate

the initiation of motor responses by the initiation of motor responses by environmental stimuli.environmental stimuli.

The VTA seems to be involved in The VTA seems to be involved in “rewarding” behavior. Note this is not “rewarding” behavior. Note this is not the same as feeling pleasure. The VTA the same as feeling pleasure. The VTA pairs behavior or sensation with a pairs behavior or sensation with a feeling of satisfaction.feeling of satisfaction.

Dopaminergic System

Neurons from this system release Acytelcholine (ACh)Neurons from this system release Acytelcholine (ACh) This system has three cores: Medial septal nucleus (MSN), the Basal This system has three cores: Medial septal nucleus (MSN), the Basal

nucleus of Meynert (BNM), and the Pontomesencephalotegemtal nucleus of Meynert (BNM), and the Pontomesencephalotegemtal complex (PC).complex (PC).

Destinations:Destinations: MSN projects to the HippocampusMSN projects to the Hippocampus BNM projects to the cerebral cortexBNM projects to the cerebral cortex PC projects to the thalamusPC projects to the thalamus

The Cholinergic System

Effects:Effects: The effects of the MSN and BNM are The effects of the MSN and BNM are

unclear but there is evidence that they unclear but there is evidence that they are involved in the laying down of are involved in the laying down of memoriesmemories Damaged to these areas linked to Damaged to these areas linked to

Alzheimer’s diseaseAlzheimer’s disease The PC seems to be involved in sensory The PC seems to be involved in sensory

filtering by the thalamus.filtering by the thalamus.

Cholinergic System

Hallucinogens (e.g. LSD)Hallucinogens (e.g. LSD) Thought to stimulate the Serotonergic system.Thought to stimulate the Serotonergic system.

Stimulants (e.g. cocaine, amphetamines):Stimulants (e.g. cocaine, amphetamines): Feelings of heightened awareness.Feelings of heightened awareness. Evidence shows these drugs inhibit the Evidence shows these drugs inhibit the

reuptake of NE and DA, causing prolonged reuptake of NE and DA, causing prolonged exposure of receptors to these exposure of receptors to these neurotransmitters.neurotransmitters.

In the case of DA, this can reward drug use In the case of DA, this can reward drug use behavior.behavior.

Effects of Drugs on Diffuse Modulatory Systems

Effects of Drugs on Diffuse Modulatory Systems