1. BIO 132 Neurophysiology Lecture 34 Diffuse Modulatory System

2. Lecture Goals: Understanding the advantage of having a diffuse modulatory system Understanding the advantage of having a diffuse modulatory system Understanding the differences between the four diffuse modulatory systems Understanding the differences between the four diffuse modulatory systems

3. We will discuss four different diffuse modulatory systems in the brain: We will discuss four different diffuse modulatory systems in the brain: Noradrenergic Noradrenergic Cholinergic Cholinergic Dopaminergic Dopaminergic Serotonergic Serotonergic 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

4. Each system has a small core of neurons (only a few thousand) 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 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 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) 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. Each system only modulates the actions of other neurons and does not turn them on or off. Like adjusting the volume on a radio instead of the power Like adjusting the volume on a radio instead of the power Commonalities of the Diffuse Modulatory Systems

5. Boutons en passant is a French term meaning “buttons in passing”. 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 voltage-gated calcium channels and secretory vesicles but some neurons can have these areas strung along their axons like a string of pearls. An axon terminal (“terminal bouton”) is what we normally think of as having the voltage-gated 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) The synapses are not terminal but rather run along axons (called boutons en passant) Boutons en Passant

6. Neurons from the core meander through the brain, and when activated, release neurotransmitter from thousands of sites along the axon. 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. Any neuron in close proximity is affected. Boutons en Passant Axon terminal (terminal bouton) Boutons en passants Cell body/dendrites

7. Neurons from this system release norepinephrine (NE) 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. The core of this system is called the locus coeruleus (meaning “blue spot”) and is located in the pons. Each locus coeruleus (there is one on each side) contains ~12,000 neurons. Each locus coeruleus (there is one on each side) contains ~12,000 neurons. The Noradrenergic System Destination: Nearly everywhere in brain (Cerebral cortex, cerebellum, thalamus, hypothalamus, spinal cord, etc) Destination: Nearly everywhere in brain (Cerebral cortex, cerebellum, thalamus, hypothalamus, spinal cord, etc) A single neuron from this system can make connections with over 250,000 neurons. A single neuron from this system can make connections with over 250,000 neurons.

8. Stimulus: Novel, unexpected, non-painful stimuli (has low activity while sitting quietly) Stimulus: Novel, unexpected, non-painful stimuli (has low activity while sitting quietly) Effect: Thought to make neuronal signalling and processing faster and more efficient (increases the signal to noise ratio) Effect: Thought to make neuronal signalling and processing faster and more efficient (increases the signal to noise ratio) Noradrenergic System

9. Neurons from this system release serotonin (5-HT) Neurons from this system release serotonin (5-HT) This system cores are located in the nine Raphe nuclei (located in the brain stem). This system cores are located in the nine Raphe nuclei (located in the brain stem). The Serotonergic System Destination: Everywhere in the central nervous system Destination: Everywhere in the central nervous system Superior Raphe project up to the cortex Superior Raphe project up to the cortex Inferior Raphe project down the spinal cord Inferior Raphe project down the spinal cord

10. Stimulus: Most active during active awake states Stimulus: Most active during active awake states Effects: Effects: Superior Raphe seem to be involved in regulating sleep/wake states. They have also been implicated in altering mood and certain emotional behaviors. 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. Inferior Raphe inhibit nocioception in the spinal cord. Serotonergic System

11. Neurons from this system release dopamine (DA) Neurons from this system release dopamine (DA) This system has two cores: Substantia nigra (SN) and the Ventral tegmental area (VTA). This system has two cores: Substantia nigra (SN) and the Ventral tegmental area (VTA). Destinations: Destinations: SN projects to the Basal ganglia SN projects to the Basal ganglia VTA projects to the Frontal cortex VTA projects to the Frontal cortex The Dopaminergic System

12. Effects: Effects: The Substantia nigra seems to facilitate the initiation of motor responses by environmental stimuli. 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. 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. Dopaminergic System

13. 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 nucleus of Meynert (BNM), and the Pontomesencephalotegemtal complex (PC). This system has three cores: Medial septal nucleus (MSN), the Basal nucleus of Meynert (BNM), and the Pontomesencephalotegemtal complex (PC). Destinations: Destinations: MSN projects to the Hippocampus MSN projects to the Hippocampus BNM projects to the cerebral cortex BNM projects to the cerebral cortex PC projects to the thalamus PC projects to the thalamus The Cholinergic System

14. Effects: Effects: The effects of the MSN and BNM are unclear but there is evidence that they are involved in the laying down of memories The effects of the MSN and BNM are unclear but there is evidence that they are involved in the laying down of memories Damaged to these areas linked to Alzheimer’s disease Damaged to these areas linked to Alzheimer’s disease The PC seems to be involved in sensory filtering by the thalamus. The PC seems to be involved in sensory filtering by the thalamus. Cholinergic System

15. 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 reuptake of NE and DA, causing prolonged exposure of receptors to these neurotransmitters. Evidence shows these drugs inhibit the reuptake of NE and DA, causing prolonged exposure of receptors to these neurotransmitters. In the case of DA, this can reward drug use behavior. In the case of DA, this can reward drug use behavior. Effects of Drugs on Diffuse Modulatory Systems