Synaptic transmission
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Transcript of Synaptic transmission
Synaptic transmission
Chapter 6
pages 156 - 169
Information transmission
Action potentials (APs) initiated by depolarizing stimulus
Two general sources of depolarizing stimulus in neurons Receptor potentials from sensory transduction Information transmission between neurons
APs are intracellular events that encode information Limited to individual cells by the cell membrane
Information transmission
Transmission of information usually requires multiple cells Convergence - multiple cells with a single target Divergence - single cell with multiple targets
Need mechanism to “inform” target cells of APs Two types of mechanisms for transmitting
information encoded by APs Direct electrical coupling Release of chemical messengers
Electrical coupling
Cells are connected by ion channels that span two lipid bilayers
AP in one cell creates a voltage difference Ions flow down voltage gradient and depolarize second cell Advantages
Very rapid transmission of information
Disadvantages Does not reflect all-or-none nature of APs (any depolarization is
transmitted) Effects on target cell limited to depolarization or hyperpolarization
Electrical coupling
Electrical coupling
Used to coordinate contraction in cardiac and smooth muscle Coordinated contraction of heart to optimize blood flow Coordinated contraction of smooth muscle lining digestive
system and other organs Recently found to have important role in some
areas of the brain Synchronizes oscillatory activity in small networks of
interneurons May be important for timing or gating of information
transmission
Chemical coupling
AP can lead to release of chemical messenger Hormones Neurotransmitters
Advantages Ligand release coupled to APs Can evoke a variety of responses in target cell One way communication
Disadvantages Slower than electrical coupling
Juxtaposition of chemical release and target receptors reduces transmission delay
By far most common method of information transmission in body Neuron → neuron Neuron → muscle Neuron → gland or organ
Which of the following is an advantage of electrical coupling?
1 2 3 4 5
20% 20% 20%20%20%1. Signal initiated only in response to APs
2. Faster than chemical coupling
3. Produces a variety of postsynaptic effects
4. Maintains one way communication
5. All of the above
Synapse structure
Presynaptic – transmitting information Postsynaptic – receiving information Synaptic terminal protrudes from axon of presynaptic cell
Usually small size (100 – 500 nm across) Contains vesicles of neurotransmitter ligand Postsynaptic density on postsynaptic cell dendrite contains
neurotransmitter receptors Ionotropic (change ions) receptors are ligand-gated ion channels Metabotropic (change metabolism) receptors initiate intracellular
signaling cascades Presynaptic terminal and postsynaptic density separated by
very small (10 – 20 nm) synaptic cleft This minimizes transmission time from presynaptic → postsynaptic
The Synapse
Presynaptic release of neurotransmitter
Neurotransmitter release initiated by AP propagating into presynaptic terminal
Large transient depolarization of presynaptic terminal opens voltage-gated Ca2+ channels
Increase in intracellular free Ca2+ initiates a cascade of events that result in exocytosis of vesicles containing neurotransmitter Vesicle membranes contain specialized Ca2+ binding proteins SNARE proteins facilitate docking of vesicles on inner surface of
plasma membrane Ca2+ binding protein synaptotagmin initiates fusion of vesicle and
plasma membrane for exocytosis
Presynaptic release of neurotransmitter
Higher presynaptic [Ca2+]i increases rate of exocytosis until saturation [Ca2+]i increases with number and rate of APs traveling toward
presynaptic terminal Neurotransmitter ligand diffuses across synaptic cleft and
binds to postsynaptic receptors Ligand binding is terminated by enzymatic breakdown within
cleft or active reuptake of neurotransmitter molecules by neighboring cells
Many psychiatric and psychotropic drugs function to prevent neurotransmitter uptake or breakdown Prolongs ligand - receptor binding by maintaining ligand
concentration in synaptic cleft
How does a depolarization from a presynaptic AP lead to the release of neurotransmitter?
1 2 3 4
25% 25%25%25%1. Ca2+ influx through voltage-gated Ca2+ channels
2. K+ influx through voltage-gated K+ channels
3. Na+ influx through voltage-gated Na+ channels
4. Vesicle docking proteins are voltage-gated
Postsynaptic potentials
Neurotransmitter binding can open ligand-gated ion channel on postsynaptic density
Resulting ionic flux can be depolarizing or hyperpolarizing depending on ionic species that permeates open channels
EPSP – excitatory postsynaptic potential Depolarization due to opening of Na+ or Ca2+ permeant
ligand-gated ion channels Termed “excitatory” since Vm of postsynaptic cell is
pushed closer to AP threshold
Postsynaptic potentials
IPSP – inhibitory postsynaptic potential Hyperpolarization due to opening of K+ or Cl- permeant ligand-gated
ion channels Termed “inhibitory” since Vm of postsynaptic cell is pushed farther
from AP threshold
PSPs – general term for both EPSPs and IPSPs Characteristic time course due to diffusion, binding and
unbinding of neurotransmitter ligand Desensitization - closing of ligand-gated ion channel while
ligand is still bound to receptor Similar to inactivation of voltage-gated Na+ channel during
depolarization Requires removal of ligand before channel can open again
A neurotransmitter activates a ligand-gated K+ channel. This should produce:
1 2 3 4
25% 25%25%25%1. An EPSP
2. An IPSP
3. Both
4. Neither
Synaptic integration
In most neurons, a single EPSP will not drive postsynaptic Vm past AP threshold
Postsynaptic APs are typically evoked by simultaneous synaptic inputs from convergent sources
Temporal summation – rapid EPSPs from same presynaptic terminal Example: repetitive activation of terminal labeled “A”
Spatial summation – simultaneous EPSPs from different presynaptic terminals Example: simultaneous activation of terminals labeled “A” and “B”
IPSPs will serve to negate EPSPs or drive Vm below AP threshold
Synaptic strength
Unlike APs, PSPs are graded and can vary in amplitude and time course
Presynaptic factors affecting PSP amplitude and time course Rate of neurotransmitter synthesis Amount of neurotransmitter per vesicle Amount of Ca2+ entry per presynaptic AP Number of vesicles Up or down regulation of neurotransmitter release via intracellular signaling
molecules Synaptic cleft factors affecting PSP amplitude and time course
Cleft geometry and neurotransmitter diffusion Uptake or breakdown of neurotransmitters
Postsynaptic factors affecting PSP amplitude and time course Spatial or temporal summation of PSPs Number of neurotransmitter receptors Up or down regulation of neurotransmitter receptors via intracellular
messengers
Possible Actions of Drugs on a Synapse
Synaptic strength
Many drugs called neuromodulators act to modulate neurotransmitter release
Other neuromodulators prevent activation of neurotransmitter receptor by ligand
Many presynaptic terminals have axo-axonic synapses to modulate neurotransmitter release
Many presynaptic terminals have autoreceptors that bind to transmitters released from same terminal Serves as negative feedback to prevent excess release of neurotransmitter
Many diseases affect synaptic transmission Tetanus – bacterial toxin that destroys proteins involved in inhibitory
neurotransmitter release Most toxins from venomous species are potent antagonists of voltage-
and ligand-gated ion channels Paralyze or kill prey by preventing APs or synaptic transmission
Presynaptic (axo-axonic) synapse
A drug increases an EPSP produced by a pre-synaptic input. This drug could be acting by:
1 2 3 4
25% 25%25%25%1. Increased reuptake of the neurotransmitter
2. Increased Ca2+ influx through voltage-gated Ca2+ channel
3. Presynaptic autoreceptor that decreases vesicle docking
4. Postsynaptic GPCR that decreases response of ligand-gated ion channel
Neurotransmitters
-ergic refers to the type of neurotransmitter a neuron releases Acetylcholine (ACh) and cholinergic neurotransmission
Primary excitatory neurotransmitter in PNS Used by somatic and preganglionic autonomic neurons Degraded by enzyme acetylcholinesterase Nerve gas Sarin inhibits acetylcholinesterase
Catecholamines – derivatives of tyrosine Includes dopamine and epinephrine Broken down by monoamine oxidase (MAO) MAO inhibitors used to treat psychiatric disorders Dopamine linked to Parkinson’s disease Epinephrine (adrenaline) and norepinephrine (noradrenaline)
regulate heart rate and blood pressure
Neurotransmitters
Other biogenic amines Called biogenic amines due to synthesis from amino acid precursors Serotonin or 5-hydroxytryptophan (5-HT) associated with alertness,
appetite, emotional state Prozac blocks 5-HT uptake, LSD blocks 5-HT receptors Histamine associated with immune and injury responses Antihistamines to prevent cold symptoms and inflammation
Amino acids Major source of excitatory and inhibitory neurotransmitters in brain Glutamate receptors (GluRs) are majority of excitatory ligand-gated
ion channels in brain Glycine and GABA (-amino butyric acid) are majority of inhibitory
ligand-gated ion channels in brain Many drugs including barbiturates and benzodiazepines (Valium) act
at GABA receptors
Neurotransmitters
Neuropeptides – small polypeptides Mainly involved in pain sensation and analgesia Opiate receptors target of morphine and codeine
Other neurotransmitters ATP can act as neuromodulator Diffusable gases nitric oxide and carbon monoxide act at
intracellular receptors Not classical neurotransmitter because they don’t require
vesicles to be released Release is of nitric oxide and carbon monoxide is driven
by presynaptic production