synapses I and II Flashcards
What are the two major categories of synapses? Briefly describe each.
Electrical: communication via gap junctions
Chemical: indirect communication via neurotransmitter release and post-synaptic receptor use
Describe the anatomical and physiological characteristics of gap junctions and
explain the features of electrical signaling
Presynaptic neuron and post synaptic membrane are connected via gap junctions. Vesicles and neurotransmitters are not needed, and ions can flow through the junction to propagate the electrical signal
What is the major benefit of electrical signaling? What is this major downside?
They’re fast, but they can’t propagate far
Describe the anatomical and physiological characteristics of chemical synapses.
A presynaptic and postsynaptic neuron are separated by a synaptic cleft. Neurotransmitters are released from the presynaptic neuron and bind to receptors on the post synaptic membrane. this influences channels that will impact ion channels in the post synaptic cell
what are the two major chemical receptor types?
Ionotropic: ligand gated ion channels
Metabotropic: alter metabolism in the postsynaptic cell via G protein signaling pathways
Describe the steps of synaptic transmission (chemical)
-AP invades the presynaptic terminal
-Depolarization of presynaptic terminal causes voltage gated calcium channels to open and influx of calcium into the bouton
-Calcium causes vesicles to fuse with presynaptic membrane
-Neurotransmitter is released into the synaptic cleft
-Postsynaptic channels open/close, and excitatory or inhibitory postsynaptic potential occurs
-Astrocytes/enzymatic degradation remove neurotransmitter
What is syntaxin?
A protein in the presynaptic membrane important for bringing the vesicle closer to the presynaptic membrane
What is synaptobrevin?
A protein in the vesicle important for bringing the vesicle closer to the presynaptic membrane
What is SNAP-25?
A protein in the vesicle important for bringing the vesicle closer to the presynaptic membrane
Describe how botulinum toxin impacts the successful synapse of neurotransmitters
Proteases that cleave the vesicle/membrane associated anchoring proteins, blocking the ability for calcium to allow fusion of the vesicle. Because of this, the neurotransmitter isn’t released. Primarily target Ach, limiting skeletal muscle movement
Describe how tetanus toxin impacts the successful synapse of neurotransmitters
Protease that cleaves synaptobrevin to prevent vesicle docking and priming; tends to impact inhibitory neurons in the spinal cord and causes uncontrolled skeletal muscle contraction
Describe how latrotoxin impacts the successful synapse of neurotransmitters
Binds to vesicle proteins and causes calcium independent vesicle fusion and neurotransmitter release
What is Lambert-Eaton syndrome?
Muscle weakness caused by auto-antibodies binding to calcium channels on motor axons
What is NMDA encephalitis?
Auto-antibodies binding to Glu1; associated with hallucination
What is the major excitatory neurotransmitter in the brain? What ion channels does it use?
Glutamate; sodium, potassium, and calcium
What is the major inhibitory neurotransmitter in the brain? What ion channels does it use?
GABA; chloride
Where are type I glutamate synapses found? what is their post-synaptic density?
Dendritic spines; they have prominent post-synaptic density
Where are type II GABA synapses found? what is their post-synaptic density?
The dendritic shafts, soma, or axon. They have small post-synaptic density
GABAa is a(n) ___ receptor, while GABAb is a(n) ___ receptor
ionotropic, metabotropic
Describe AMPA receptors
Ionotropic glutamate receptors. Fast kinetics and low calcium permeability; require high concentration of glutamate to be activated
Describe NMDA receptors
Ionotropic glutamate receptors. Slow kinetics and high calcium permeability; they require glycine in addition to glutamate for activation
Describe the cycle of moving glutamate between neurons and glia/other neurons
-Glutamine converts to glutamate in a presynaptic neuron
-Glutamate gets packaged into VGLUT transport vesicles, when is then released via exocytosis
-Transporters take up extracellular glutamate in the synaptic cleft
-Glutamine synthetase breaks glutamate to glutamine, which then gets shuttled between glia and neurons by SN1/SAT2
Describe GCPR receptors
Metabotropic glutamate receptors that activate intracellular signaling pathways.
Magnesium ion can block which receptor at resting membrane potential?
NMDA
Describe GABAa receptors: structure and function
GABAa: ionotropic. A pentameric structure surrounding an aqueous pore. The pore conducts chloride, typically entering the cell, hyperpolarizing the neuron and creating an IPSP. (The chloride can be leaving the cell via this method). Because of this, GABAa in adults is typically considered inhibitory. In infants, it is mildly stimulatory
Describe GABAb receptors
G protein coupled receptors that are metabotropic. They’re highly associated with GIRK channels, using the outward flow of potassium to hyperpolarize the cell. This receptor is slower than GABAa.
Describe how summation of IPSPs and EPSPs determines whether an action
potential is generated
Single EPSPs are typically subthreshold. If we stimulate multiple EPSPs closer together, we can reach action potential. This is also dependent on lower amounts of IPSPs, as those can decrease depolarization abilities of EPSP
Describe temporal summation
Two stimuli occurring closer together in time, making their combined effort more likely to cause an action potential
Describe spatial summation
Two stimuli occurring closer together in space, making their combined effort more likely to cause an action potential
Describe the actions of modulatory neurotransmitters
The presence of modulatory neurotransmitters can increase or decrease excitability. With the same stimulus, the presence of these neurotransmitters can greatly increase or decrease the output.
describe how excitability can be modulated presynaptically
Presynaptic: inhibit release calcium channels and SNARE proteins that allow for vesicle fusion and release of neurotransmitter
describe how excitability can be modulated postsynaptically
Postsynaptic: opens K+ channels to reduce excitability. GABAb is a good example.
Discuss the role of G proteins in the primary signaling pathways of neurotransmitter
A neurotransmitter binds to the G protein, causing the GDP on the subunit for exchange for GTP. The beta and gamma subunits then release and go on to impact signaling within the cell.
Describe G protein signaling with Gs
Stimulatory; activates adenyl cyclase, which activates cAMP, which then activates PKA. Typically associated with beta adrenergic receptors (both glutamate and GABA)
Describe G protein signaling with Gi
Inhibitory; deactivates adenalyl cyclase, prevents activation of PKA
Describe G protien signaling with Gq
Activates phospholipase c, which activates IP3 and DAG. IP3 opens ca channels and DAG activates PKC, both of which increase stimulatory actions. Typically associated with glutamate
describe nitric oxide as an unconventional neurotransmitter
generated when neuronal activity increases and calcium permeable channels are active. It can freely diffuse out of the axon and can have influence far from where it was made. It can also bind to iron heme groups (aguanyl cyclase), leading to generation of second messengers (cGMP) and activate PKG. it is a retrograde signaling method
describe endogenous cannaboids as an unconventional neurotransmitter
made by the neurons and resemble THC. Receptors are found on presynaptic terminals and GABA and glutamate neurons to regulate release of neurotransmitter. It is a retrograde signaling method (made in a postsynaptic cell, and diffuse back to the presynaptic cell).
describe acetylcholine
Found in septal nuclei in the brain. They use nicotinic acetylcholine receptors as well as muscarinic G protein receptors
Describe catecholamines
Dopamine, NE, and epinephrine. Dopamine neurons are found in substantis nigra and ventral tegmental area. NE are found in the locus coeruleus. These bind metabotropic receptors, and their impact is dependent on specific monoamine transporters that take them back into the nerve terminal.
Describe serotonin
Neurons originate in the raphe nuclei and pons. They typically bind to metabotropic receptors, but there is one type of ionotropic receptor. Their action is terminated by serotonin transporters that take it back into the neuron
Describe peptide neurotransmitters
Proteins made in the nucleus that travel down the axon. Once they reach the terminal, they are cleaved to become active. They typically activate G protein coupled metabotropic receptors on presynaptic and postsynaptic membranes (they regulate excitability)
