Ch 3. Synapses and Synaptic Transmission Flashcards
Where does neural communication occur?
at synapses
What can be interfered with in diseases that disrupt synaptic communication?
neural function
Where do most drugs that affect the CNS act at?
the synapse
What is a synapse?
A specialized site where a neuron communicates with another neuron or effector cell
What 2 cells are involved in synapses?
presynaptic
postsynaptic
What are presynaptic cells?
The neuron conducting the electrical signal toward the synapse
What are presynaptic terminals?
Located at the end of the axon of the presynaptic cell
Vesicles containing neurotransmitters are located here
Site of neurotransmitters release
What are postsynaptic cells?
The cell which receives the signal from the presynaptic cell
What is a postsynaptic terminal?
The membrane region of the postsynaptic cell (the receiving cell) that contains receptors for neurotransmitters
What is the synaptic cleft (gap)?
A narrow space filled with interstitial fluid that separates presynaptic cell and postsynaptic cell
What is the neuromuscular junction?
A synapse between a neuron and a muscle cell
What is a Neuroglandular Junction?
A synapse between a neuron and a gland
What are the steps of events that occur at the synapse?
- An AP reaches presynaptic terminal
- Presynaptic terminal depolarizes causing voltage-gated Ca+ channels in presynaptic terminal to open
- Ca+ enter presynaptic terminal
- Ca+ triggers movement of synaptic vesicles, containing neurotransmitters, toward a release site in the presynaptic terminal
- Synaptic vesicles fuse with presynaptic membrane and release neurotransmitter into the synaptic cleft
- The neurotransmitter crosses the synaptic cleft
- The neurotransmitter binds to its specific receptor on a membrane protein which contains a chemical-gated ion channel in the postsynaptic membrane
- The membrane protein changes shape which will either:
a. Open the ion channel associated with the membrane protein receptor, or
b. Activate intracellular messengers associated with the membrane receptor
Does the binding of a neurotransmitter on the Postsynaptic Receptor open an ion channel directly or indirectly?
either
What can binding of a neurotransmitter on the Postsynaptic Receptor activate?
intracellular messengers associated with
the membrane receptor
What are the types of synapses based on?
which parts of the pre- and post-synaptic membrane form the synapse
What is an axodendritic synapse?
connection between axon to dendrite
What is an axosomatic synapse?
connection between axon to cell body
What is an axoaxonic synapse?
connection between axon to axon
How many synaptic inputs can a single neuron have?
A single neuron can have multiple synaptic inputs in each region
What 3 things are postsynaptic cells affected by?
The total number of action potentials reaching the presynaptic axon terminal
Strength of the stimulus to the presynaptic cell
Duration of the stimulus to the presynaptic cell
What is postsynaptic potential?
An electrical change in the postsynaptic membrane
It is a graded, nonpropagated electrical signal
What is postsynaptic potential the result of?
Local changes in ion concentration across the postsynaptic membrane
The effect of the stimulus in terms of postsynaptic potential can either do what?
Depolarization of the postsynaptic membrane: An Excitatory Postsynaptic Potential (EPSP)
Hyperpolarization of the postsynaptic membrane: An Inhibitory Postsynaptic Potential (IPSP)
Is a neurotransmitter that
depolarizes the Postsynaptic Membrane excitatory or inhibitory?
Excitatory because it brings the membrane potential closer to the threshold for generating an action potential
Is a neurotransmitter that
hyperpolarizes the Postsynaptic Membrane excitatory or inhibitory?
Inhibitory because it brings the membrane potential away from the threshold for generating an action potential
What is an Inhibitory Postsynaptic Potential (IPSP)?
a local neurotransmitter that hyperpolarizes the Postsynaptic Membrane
What is an Excitatory Postsynaptic Potential (EPSP)?
a local neurotransmitter that depolarizes the Postsynaptic Membrane
When does an EPSP occur?
when neurotransmitters bind to postsynaptic membrane receptors that open chemical-gated ion channels
In an EPSP when a chemical-gated ion channels open what happens next?
Leads to an influx of positively charged ions into the cell
This depolarizes the postsynaptic cell membrane
Creates an EPSP
What occurs in a summation of EPSPs vs an individual EPSP?
An individual EPSP has only a small effect on membrane potential
Summation of EPSPs can lead to generation of an action potential
When does an IPSP occur?
when neurotransmitters bind to postsynaptic membrane receptors that open chemical-gated ion channels
In an IPSP when a chemical-gated ion channels open what happens next?
Leads to the flow of Cl– into or K+ out of the postsynaptic membrane
This hyperpolarizes (more negative) the postsynaptic cell membrane and creates an IPSP
This can inhibit the generation of an action potential
What happens if EPSPs coincide with IPSPs?
Summation of EPSPs and IPSPs determines whether the postsynaptic membrane is Depolarized (Excited) or
Hyperpolarized (Inhibited)
An AP will occur only when what is sufficient?
Only if depolarization is sufficient to reach membrane threshold
What occurs in spatial summation of ESPSs and IPSPs?
changes in membrane potential can cancel each other out
What are presynaptic facilitation and inhibition?
synaptic mechanisms by which neurons may affect the activity of other neurons
What is the function of presynaptic facilitation and inhibition?
Regulate the ability of the presynaptic cell to release neurotransmitters
Can either increase (facilitate) or decrease (inhibit) the rate of neurotransmitter release at the presynaptic membrane
What structures are involved in presynaptic facilitation and inhibition?
3 Neurons
An Axoaxonic Synapse
What does an interneuron do?
Releases neurotransmitters that bind to receptors on the axon terminal of the presynaptic neuron
What are the two possible actions of the binding of the neurotransmitter released from interneurons?
Increase (facilitate) the amount of Ca2+ that enters the presynaptic terminal
Decrease (inhibit) the amount of Ca2+ that enters the presynaptic terminal
When neurotransmitters from interneurons increase the amount of Ca2+ entering the presynaptic terminal what will this lead to?
This will lead to an increase in the amount of neurotransmitter that will be released by the presynaptic neuron
Results in increased stimulation (facilitated) of postsynaptic neuron
Increasing both the Degree of Depolarization and Likelihood of an Action Potential
When neurotransmitters from interneurons decrease the amount of Ca2+ entering the presynaptic terminal what will this lead to?
This will lead to a decrease in the amount of neurotransmitter that will be released by the presynaptic neuron
Results in decreased stimulation (inhibited) of postsynaptic neuron
Decreasing both the Degree of Depolarization and Likelihood of an Action Potential
What are the steps in Presynaptic Facilitation?
- AP arrives in interneuron
- serotonin release at interneuron
- activation of calcium channels at presynaptic terminal
- AP arrives at presynaptic terminal
- More calcium enters presynaptic terminal
- More neurotransmitter released at presynaptic terminal
- increased effect on postsynaptic membrane
What are the steps in Presynaptic Inhibition?
- AP arrives in interneuron
- GABA release at interneuron
- inactivation of calcium channels at presynaptic terminal
- AP arrives at presynaptic terminal
- Less calcium enters presynaptic terminal
- Less neurotransmitter released at presynaptic terminal
- Reduced effect on postsynaptic membrane
What are the four major categories of neurotransmitters?
Biogenic amines (monoamines)
Amino acids
Neuropeptides
Dissolved Gases
Name the Biogenic Amines (Monoamines)
Catecholamines
- Epinephrine
- Norepinephrine
- Dopamine
Serotonin(5-hydroxytryptamine; 5-HT)
Histamine(Only recognized in the CNS as a neurotransmitter)
Name the Amino Acids
Glutamate
Aspartate
GABA
Glycine
Name the Neuropeptides
Substance P
OpioidPeptides
- Endorphins
- Enkephalins
- Dynorphin
Name the dissolved gases
Carbon Monoxide
Nitric Oxide
Define neurotransmitter
chemicals released by synaptic terminals for the purpose of transmitting information from the presynaptic cell to a postsynaptic cell
What is Neurotransmitter Synthesis?
Some neurotransmitters are synthesized in the:
- Neuron cell body and transported to the axon terminal (e.g., neuropeptides such as Substance P)
- Axon terminal (e.g., ACh)
Where are neurotransmitters released from?
the axon terminal of a presynaptic neuron
What happens with neurotransmitters at the postsynaptic cell?
Bind onto receptors located on the membrane of a postsynaptic cell to cause a direct response in the postsynaptic cell
An excitatory or inhibitory response by a neurotransmitter on the postsynaptic membrane depends on what?
Specific neurotransmitter
Receptor on the postsynaptic membrane
How do neurotransmitters directly affect the postsynaptic cell?
By binding to an Ionotropic Receptor and directly activating a membrane channel
How do neurotransmitters indirectly affect the postsynaptic cell?
By binding to a Metabotropic Receptor and activating proteins inside the postsynaptic cell that stimulate
- The opening of a membrane channel or
- Changes inside the cell
What are Neuromodulators?
Signaling compounds that are released from axon terminals and are capable of modulating (enhance or suppress) synaptic transmission by modulating effects of neurotransmitters at the synapse
Can affect the response of a neuron to other neurotransmitters
How do neuromodulators react with presynaptic receptors?
They bind to receptors on a presynaptic neuron and can alter the rate of neurotransmitter release by a presynaptic neuron
How do neuromodulators react with postsynaptic receptors?
They bind to receptors on a postsynaptic neuron and can change the postsynaptic cell’s response to the neurotransmitter
They can producing slower or longer lasting changes in membrane excitability
Neuromodulators resulting in either excitatory or inhibitory actions depends on what?
the postsynaptic receptor
Which major category of neurotransmitters are neuromodulators typically fall into?
neuropeptides
Can chemicals be both a Neurotransmitter and Neuromodulator?
yes
How do the effects of neuromodulators compare with those of neurotransmitters?
Neuromodulator effects manifest slower than those of neurotransmitters
Neuromodulators effects usually last longer than those of neurotransmitters
What is the span of release for Neuromodulators?
May be:
- Local
- Widespread: Can diffuse throughout an area and act at distance from the site of release so they can affect groups of neurons or effector cells
What are Neuropeptides?
a distinct class of chemical signaling molecules
Where are neuropeptides synthesized and subsequently transported to?
synthesized in the neuron cell body and transported to the axon terminal
What do neuropeptides function as?
Neurotransmitters
Neurohormones (e.g., ADH, Oxytocin)
Neuromodulators
Name the 2 neuropeptides
Substance P: Acts as a neurotransmitter and neuromodulator
OpioidPeptides
- Endorphins
- Enkephalins
- Dynorphin
What is Acetylcholine (ACh)?
An excitatory neurotransmitter
Where do neurons release Acetylcholine (ACh)?
In the Autonomic Nervous System
At the skeletal neuromuscular junction
In the brain
What is Glutamate?
An excitatory neurotransmitter in the CNS
Important in Learning and Memory
What happens if there is excessive release of glutamate and when would this occur?
May contribute to neuron death following CNS damage (e.g., stroke)
Name the amino acid neurotransmitters
Glutamate
Aspartate
GABA
Glycine
What is glycine?
Mainly acts as an inhibitory neurotransmitter primarily in the Brainstem and Spinal Cord
Inhibits the postsynaptic membrane
What is GABA (Gamma-aminobutyric Acid)?
The major inhibitory neurotransmitter in the CNS particularly with interneurons in the spinal cord
What is GABA essential for?
the overall balance between neuronal excitation and inhibition that is vital to normal brain function
What are low levels of GABA associated with?
seizures
Name the catecholamines
Epinephrine
Norepinephrine
Dopamine
What is dopamine?
Usually an inhibitory neurotransmitter
Can be excitatory neurotransmitter
Where is dopamine produced?
Produced by neurons in the substantia nigra (midbrain)
What are the functions of dopamine?
Plays an essential role in the control of movement
Cognition
Behavior
Affects the ability to experience pleasure and reward (therefore, affects behavior)
What are low levels of dopamine associated with?
Depression
Loss of motor control (Parkinson’s Disease)
What are elevated levels of dopamine associated with?
Schizophrenia
Anxiety
Which drugs affect dopamine and how?
-cocaine and amphetamines: inhibit the re-uptake ofdopamine into the presynaptic neuron which prolongs dopamine activity, by allowing it to continueto bind and activate receptors-
Leads to the euphoria associated with cocaine use
-Amphetamines: Increase the release of dopamine and block dopamine and NE reuptake
What is norepinephrine?
Usually an excitatory neurotransmitter
Can be inhibitory neurotransmitter
Where is norepinephrine released in the CNS and PNS?
CNS
- Brainstem
- Thalamus
- Hypothalamus
PNS
- Postganglionic Sympathetic Fibers
- Adrenal Medullae
What are the functions of norepinephrine?
Involved in the “fight-or-flight” response
Increased arousal and alertness
Increased blood pressure
Increased heart rate
Breakdown of glycogen
What are elevated levels of norepinephrine associated with?
Fear and panic
Increased sympathetic nervous system activity
Increased panic attacks and stress in individuals with PTSD
What are low levels of norepinephrine associated with?
Fatigue
Depression
ADHD
Decreased sympathetic nervous system activity
Is Serotonin excitatory or inhibitory?
Mainly acts as an inhibitory neurotransmitter
What is serotonin released by?
Neurons in the CNS
Neurons in the enteric nervous system
Enterochromaffin cells of the gastrointestinal mucosa
What are the functions of serotonin?
Improved Mood
Pain Regulation
Decreased Appetite
Sleep
Inhibits Gastric Acid Secretion
Modulation of GI Motility
What are low levels of serotonin associated with?
Depression
Suicidal Behavior
What are elevated levels of serotonin associated with?
Agitation
Rapid Heart Rate
What is histamine?
A compound released from Mast Cells and Basophils
Recognized as an Excitatory and Inhibitory neurotransmitter only in the CNS
Where are histamine released from?
from neurons with cell bodies in the hypothalamus
What roles do histamine play in the CNS?
Learning and Memory
Sleep-wake Cycle
Name the neuropeptides
Substance P
OpioidPeptides
- Endorphins
- Enkephalins
- Dynorphin
What does substance P act as?
Acts as a neurotransmitter and neuromodulator
What are the functions of Substance P?
It enhances the perception of pain
In the brain it acts as a neuromodulator to produces long-duration excitation of postsynaptic cells
Can assist in the immune response
What is the mechanism of pain involved with Substance P?
Tissue injury causes the release of various inflammatory mediators from the damaged tissue
- Cytokines
- Serotonin
- Prostaglandins
- Bradykinin
- H+
These mediators can stimulate nociceptors directly
What are nociceptors?
The free nerve endings of primary afferent Aδ (A Delta) and C Fibers
What happens when nociceptors are stimulated?
They transmit an action potential that results in the release of Substance P from the afferent terminal endings of the neuron fibers in the
- Dorsal Gray Horn
- Skin
- Muscle
- Joints
What happens when Nociceptor-related primary afferent fibers synapsing in the dorsal gray horn of the spinal cord
release Substance P?
stimulates a 2nd Order Neuron to transmit pain signals upward to the brain
What is Peripheral Sensitization?
Substance P acts to reduce the activation threshold of nociceptors so less stimulation is required to trigger an action potential
What do Endogenous Opioids
act as?
Neurotransmitters
Neuromodulators
Endogenous Opioids bind to the same receptors as what?
exogenous opioid drugs
What is the function of endogenous opioids?
Inhibit neurons in the CNS that are involved in the perception of pain
Alter the rate of neurotransmitter release by the presynaptic neuron
Change the postsynaptic cell’s response to neurotransmitters
What are the 3 main families of endogenous opioids the body synthesizes to help control pain?
Endorphins
Enkephalins
Dynorphins
What is Nitric Oxide?
A lipid-soluble gas that acts as a diffusible neurotransmitter
What releases nitric oxide?
Released by neurons that innervate smooth muscle of blood vessels in the PNS and Brain
What kind of receptor does nitric oxide bind to?
Does not require a receptor on the plasma membrane to bind for activation
Diffuses through the plasma membrane and acts on a messenger system in the postsynaptic cell
What does nitric oxide cause?
vasodilation
When neurotransmitters are released into the synaptic cleft what must happen for them to have an effect?
Must bind to a specific receptor
What determines the effect of the neurotransmitter?
Effect is based on the receptor, not the neurotransmitter
There are numerous receptor subtypes for any neurotransmitter
Where are neurotransmitter receptors located?
Presynaptic Neurons
Postsynaptic Neurons
What are Presynaptic Neuron Receptors also known as?
autoreceptors
What is the function of Presynaptic Neuron Receptors (autoreceptors)?
release-regulating receptors that help monitor the amount of neurotransmitter so when its being released, they monitor if there are proper levels in the synapse and when there are enough, they slow process down
What are Presynaptic Neuron Receptors (autoreceptors) sensitive to?
the neuron’s own Chemical Signaling Molecules (e.g., neurotransmitters, neuromodulators, neurohormones)
What do Presynaptic Neuron Receptors (autoreceptors) serve as?
A negative feedback mechanism that can inhibit the release of a neuron’s own
- Neurotransmitter
- Neurohormone
- Neuromodulator
What are the 2 ways in which Neurotransmitter Postsynaptic Receptors can be classified?
Ionotropic Receptors (Ligand-gated Ion Channels)
Metabotropic Receptors (G Protein-Linked Receptors)
What do Ionotropic Receptors generally mediate in comparison to Metabotropic Receptors?
Ionotropic Receptors generally mediate rapid postsynaptic effects
Metabotropic Receptors typically produce much slower responses
What is the receptor coupled with in ionotropic receptors (Ligand-gated Ion Channels)?
an ion channel
What kind of effect do Neurotransmitters that bind to ionotropic receptors have?
Have a direct activation effect on the ion channel
What do membrane proteins on ionotropic receptors (Ligand-gated Ion Channels) act as?
Receptors (Ionotropic Receptors) and
Direct-acting Ion Channels
What are the ligand-gated channels like in the resting state?
they are closed which blocks the flow of ions through the channel
What happens when a ligand binds to its specific receptor?
The ion channel will change shape and open to allow specific ions to pass through the channel (cross the plasma membrane into or out of the cell)
How does the process of when a ligand binds to its specific receptor differ for Excitatory Neurotransmitters and Inhibitory Neurotransmitters?
The process is the same for both
What is the receptor coupled with in Metabotropic receptors (G Protein-Linked Receptors)?
The receptor is not coupled to an ion channel
The receptor is coupled to a G-protein
What kind of effect do Neurotransmitters that bind to Metabotropic Receptors (G Protein-Linked Receptors) have?
indirect activation of ion channels
When a neurotransmitter binds to the receptor the G-protein (an intracellular protein) can indirectly open ion channel
What happens when a neurotransmitter (First Messenger) binds to a Metabotropic Receptor (G Protein-Linked Receptor)?
activates the G Protein (an intracellular protein)
What are the two possible subsequent actions of an activated G protein?
Bind to a membrane ion channel causing the channel to open
or
Bind to and activate a membrane enzyme which then, through a series of steps a Second Messenger is formed. The a Second Messenger can: -Activate enzymes -Inhibit enzymes -Activate genes -Modulate Ca2+ levels in the cell
What is the general result of movement of ions across the plasma membrane?
Results in a change in the membrane potential
What is hyperpolarization?
A change in the transmembrane potential toward a more negative value than the resting membrane potential
What movements cause hyperpolarization?
Positive ions out of the cell
Negative ions into the cell
How does hyperpolarization affect neuronal activity?
Can cause inhibition of neuronal activity
How do EPSPs (excitatory postsynaptic potentials) occur in ionotropic receptors?
ion channels open and positive charges enter the postsynaptic neuron, causing an EPSP
How do IPSPs (inhibitory postsynaptic potentials) occur in ionotropic receptors?
ion channels open and the postsynaptic neuron gains negative charges or loses positive charges, causing an IPSP
Describe the Second Messenger System
- hormone (1st messenger) binds receptor
- receptor activates G protein
- G protein activates adenylate cyclase (enzyme)
- adenylate cyclase converts ATP to cAMP (2nd messenger)
- cAMP activates protein kinases
- active protein kinase triggers responses of target cell (activates enzymes, stimulates cellular secretion, opens ion channel, etc)
Continuous activation or continuous inhibition of cell receptors can affect what?
Receptor Sensitivity
- Receptor Desensitization (Inactivation)
- Receptor Supersensitivity (Hypersensitivity)
The Number of Cell Receptors
- Receptor Down-Regulation (Internalization)
- Receptor Up-Regulation (increase number of receptors)
What happens in Receptor Desensitization (Inactivation)?
When receptors are continuously stimulated the receptor can become less responsive (desensitized) due to modification of the receptor
The ligand-gated channel can close despite the continued presence of the ligand
How long does Receptor Desensitization (Inactivation) last?
Usually for just a brief period of time
Return of normal response occurs within a few minutes after the stimulus is removed
What is Receptor Supersensitivity (Hypersensitivity)?
A prolonged decrease in the stimulation of a receptor
What could Receptor Supersensitivity (Hypersensitivity) result in?
an increase in receptor sensitivity
