Exam 2 Flashcards
What is synaptogenesis?
The process by which neurons form synapses with other neurons, allowing for neural communication.
What are the key components in synaptogenesis?
Differentiation from growth cone → presynaptic terminal, molecular programs, activity involvement.
What evidence supports molecularly-instructed synapse formation?
Retinal ganglion neurons and olfactory system experiments showing specific synaptic targeting
What is the like-like rule in synapse formation?
Presynaptic cells form synapses with postsynaptic cells that express the same protein as theirs.
What is Dscam and its role in synaptogenesis?
An immunoglobulin domain protein responsible for specific synapse formation in retinal layers.
How does activity influence retinal synapse refinement?
Blocking visual activity results in less synaptic specificity and refinement.
What is the function of odorant receptors in synaptic targeting?
They help axons form synapses in the correct glomeruli in the olfactory bulb.
What happens in the cerebellum during synapse formation?
Climbing fibers synapse on Purkinje dendrites, while basket cells synapse on the axon initial segment.
What is the neuromuscular junction (NMJ)?
A synapse between a motor neuron and a muscle fiber, critical for muscle contraction
How do slow and fast muscle fibers differ?
Slow fibers use continuous low-frequency firing, while fast fibers use high-frequency bursts
What did the cross-innervation experiment show?
Motor neurons’ activity profile did not change, but MN influence muscle fiber properties by altering slow to fast and fast to slow
How does electrical stimulation affect muscle fiber type?
Tonic stimulation makes fast fibers resemble slow fibers and vice versa
What is reciprocal synaptic dialogue
Muscles influence MN survival and neurotransmitter secretion
What happens during NMJ synapse formation?
Growth cones find myotubes, nerve terminal accumulates synaptic vesicles, and basal lamina forms in synaptic cleft
then muscle matures and mutliple axons converge on single site, but go through presynaptic specialization, and the sole surviving axon terminal matures
What is the basal lamina and its role in the NMJ?
An extracellular matrix in the synaptic cleft that supports structural adhesion.
What is the function of agrin in NMJ?
Induces acetylcholine receptor clustering under the presynaptic terminal.
What does the agrin mutant NMJ indicate?
Activity (ACh) disperses receptor clusters, confirming its role in synaptic organization.
Where is Laminin Beta2 expressed?
ONLY in synaptic cleft and extrasynaptic sites of basal lamina
What was seen in mice lacking beta2 laminins?
NMJ maturation is impared; the mice have few active zones, and synaptic cleft is invaded by Schwann (glial) cells
What allows for AChR clustering?
Agrin binding to Lrp4 which recruits MuSK, resuliting in AChR clustering mediated by rapsyn
Were AChR receptors seen in Wild Type, Agrin mutants, or MuSK mutants?
Wild Type only– AChRs form under each nerve terminal by birth but other two, most AChRs have dispersed
How does the presynaptic terminal influence postsynaptic ACh receptor expression?
Activity-dependent transcription suppression in extrasynaptic nuclei.
Why are muscle membrane invaginations necessary?
They increase surface area for acetylcholine receptors and synaptic efficiency.
Why is NMJ ideal for synaptic transmission studies?
Large size, one neuron per muscle, simple neurotransmitter system.
What is acetylcholinesterase’s role in NMJ?
Breaks down acetylcholine to prevent excessive neurotransmitter accumulation.
What is the SNARE complex and its role in vesicle fusion?
A protein complex required for synaptic vesicle docking and membrane fusion.
How does botulinum toxin affect synaptic transmission?
Cleaves SNARE proteins, preventing neurotransmitter release.
What are the three mechanisms of vesicle endocytosis?
Kiss-and-run, clathrin-mediated, and bulk retrieval.
What is the function of RIM in the active zone?
Scaffolding protein that recruits calcium channels and vesicles for release.
What is myasthenia gravis?
An autoimmune disease that attacks acetylcholine receptors, weakening muscle contractions.
What are the four categories of motor diseases?
Motor neuron disease, peripheral neuropathy, NMJ disorder, and myopathy.
How does ALS affect motor neurons?
Progressive loss of motor neurons leading to muscle weakness and paralysis.
What is the difference between neuropathy and myopathy in electrical stimulation?
Neuropathy alters conduction velocity; myopathy reduces contraction force.
What happens in neural repair following axotomy?
Neurons degenerate and synaptic connections retract, affecting entire circuits.
How do Wlds mutant mice contribute to neuroregeneration studies?
Delayed axon degeneration, suggesting potential therapeutic targets.
What inhibits CNS regeneration?
Glial scars and myelin-associated inhibitors like Nogo and OMgp.
What is a conditioning lesion and its effect on CNS regeneration?
Pre-injuring a peripheral neuron enhances CNS regeneration.
How does sleep deprivation affect metabolism?
Leads to weight loss despite increased food intake, disrupting homeostasis.
What is the Synaptic Homeostasis Hypothesis of Sleep?
Sleep reduces synaptic strength to restore neural efficiency.
What are EEG patterns in different sleep stages?
Stage 1: light sleep, Stage 2: spindles/k-complexes, Stage 3-4: deep sleep, REM: wake-like.
What is narcolepsy and its cause?
A disorder caused by loss of hypocretin-producing neurons in the hypothalamus.
How does fatal familial insomnia affect sleep?
Prion disease preventing deep sleep, leading to rapid neurodegeneration and death.
What is the SOD1 gene and its role in ALS?
Mutations in SOD1 account for ~2% of ALS cases, leading to motor neuron degeneration.
What is the C9orf72 gene mutation?
A repeat expansion mutation in C9orf72 causes ALS and leads to nuclear pore complex defects.
How does the length of the C9orf72 expansion affect ALS severity?
Longer expansions lead to earlier onset and more severe ALS symptoms.
What is the SMN1 gene and its role in spinal muscular atrophy (SMA)?
SMN1 is essential for RNA splicing; its loss leads to motor neuron death in SMA.
How does SMN2 influence SMA severity?
SMN2 is a backup gene for SMN1, but it’s only ~10% functional; more SMN2 copies reduce SMA severity.
How does the Wlds mutation affect axon degeneration?
Delays axon degeneration after injury by inhibiting the Sarm gene, suggesting therapeutic potential.
What is the role of the SOCS3 gene in CNS regeneration?
SOCS3 inhibits regeneration by blocking CNTF binding to GP130; its deletion improves recovery.
What are myelin-associated inhibitors of CNS regeneration?
Nogo, OMgp, and MAG bind Nogo receptors, inhibiting axon regrowth after injury.
What are the effects of a mutation in the PMP22 gene?
Causes demyelinating neuropathy, impairing motor neuron axon function.
What does a mutation in connexin-32 cause?
Disrupts gap junctions in Schwann cells, leading to neuropathy and defective myelination.
What experiment showed odorant receptors direct olfactory axon targeting?
Deleting an odorant receptor caused its neurons to project to random glomeruli.
What experiment demonstrated activity-dependent synapse refinement in the retina?
Suturing an animal’s eyelid closed led to reduced synapse specificity and dendritic pruning.
How did the cross-innervation experiment reveal motor neuron influence on muscle type?
Switching fast and slow motor neurons altered muscle fiber properties based on activity pattern.
What experiment showed activity influences muscle fiber type?
Stimulating a fast muscle with tonic firing made it resemble a slow muscle.
What was the key finding of the bungarotoxin experiment?
Radioactive labeling of bungarotoxin showed acetylcholine receptor clustering in NMJ invaginations.
What did the optic nerve graft experiment demonstrate about CNS regeneration?
Peripheral nerve grafts allowed CNS axon regrowth, proving CNS environment inhibits regrowth.
What was the key finding in the conditioning lesion experiment?
Pre-injuring a peripheral axon enabled later regrowth of a central axon.
How did the electrical stimulation experiment reveal NMJ plasticity?
Stimulating a denervated muscle changed its acetylcholine receptor transcription pattern.
What does the fatal familial insomnia mutation cause?
A dominant prion-like misfolding protein mutation leading to progressive sleep loss and death.
How does botulinum toxin affect synaptic function?
Cleaves SNARE proteins, preventing synaptic vesicle fusion and neurotransmitter release.
What did the sleep deprivation experiment in rats reveal?
Severe metabolic and immune dysfunction, leading to death within 28 days.
How does hypocretin loss cause narcolepsy?
Hypocretin-producing neurons in the hypothalamus regulate wakefulness; their loss leads to sudden sleep onset.
How do induced pluripotent stem cells (iPSCs) help in ALS treatment?
How do induced pluripotent stem cells (iPSCs) help in ALS treatment?
What was the key discovery in the RIM protein experiment?
RIM mutants lacked proper calcium channel anchoring, disrupting neurotransmitter release.
How do BRP mutants affect active zone function?
BRP mutants lack T-bar scaffolding, impairing vesicle clustering and synaptic transmission.
What are the stages of synaptic development?
Initial contact, differentiation, maturation, and stabilization of synapses.
What is the role of laminin beta2 in NMJ?
Guides presynaptic differentiation and helps in synaptic stability.
How do agrin and acetylcholine (ACh) interact in receptor clustering?
Agrin promotes clustering, while ACh disperses excess clusters outside the synapse.
What happens in a MuSK mutant NMJ?
No acetylcholine receptor clustering occurs, leading to synapse formation failure.
What is the function of Schwann cells in NMJ development?
Support synapse formation and play a role in neurotransmitter reuptake.
How does polyinnervation change during NMJ maturation?
Multiple motor neurons initially innervate a muscle fiber, but synapse elimination selects the strongest input.
What happens to acetylcholine receptor expression if a motor neuron is cut?
Expression increases in muscle extrasynaptic areas due to loss of neurotransmission feedback.
What is the function of Rapsyn in NMJ?
Scaffolding protein required for clustering acetylcholine receptors at synapses.
What did the NMJ paralysis experiment reveal?
Blocking activity prevents synapse elimination, keeping polyinnervation intact.
What are the key components in the acetylcholine metabolism cycle?
Synthesis via choline acetyltransferase, breakdown by acetylcholinesterase, and reuptake of choline for reuse.
What are pegs in the active zone?
Likely calcium channels embedded in the presynaptic membrane, positioned near synaptic vesicles to ensure rapid neurotransmitter release.
What are ribs in the active zone?
Structural components that help tether synaptic vesicles near release sites and facilitate vesicle docking and fusion.
What are beams in the active zone?
Scaffold-like structures that support the active zone architecture and assist in vesicle organization and trafficking.
What are the three mechanisms of synaptic vesicle endocytosis?
Kiss-and-run, clathrin-mediated, and bulk retrieval, each with distinct kinetics and functional roles.
How does kiss-and-run endocytosis work?
A vesicle briefly fuses with the membrane, releases neurotransmitter through a transient pore, then closes and is recycled rapidly.
What is the kinetic profile of kiss-and-run endocytosis?
It is the fastest mechanism, occurring in milliseconds, and is used during low neurotransmitter release rates.
How does clathrin-mediated endocytosis work?
A clathrin-coated vesicle forms outside the active zone, pinches off, and is recycled into the synaptic vesicle pool.
What is the kinetic profile of clathrin-mediated endocytosis?
Occurs on the scale of seconds and is the dominant mode during moderate to high-frequency neurotransmission.
How does bulk retrieval endocytosis work?
Large membrane invaginations form during intense synaptic activity, later processed into individual vesicles via clathrin.
What is the kinetic profile of bulk retrieval endocytosis?
Slower than kiss-and-run and clathrin-mediated endocytosis, occurring over several seconds, and activated only during very high activity.
What is the role of neurotransmitters in synaptic transmission?
Neurotransmitters are chemical messengers that transmit signals across synapses by binding to receptors on the postsynaptic membrane.
What is the NMJ and why is it ideal for studying synaptic transmission?
The neuromuscular junction is a large, well-defined synapse with a single neurotransmitter (ACh) and receptor type, making it a model for studying transmission.
How is acetylcholine metabolized in cholinergic nerve terminals?
Acetylcholine is broken down by acetylcholinesterase into acetate and choline, preventing excessive signaling.
What happens if acetylcholinesterase is inhibited?
ACh accumulates in the synaptic cleft, leading to prolonged activation of receptors, causing paralysis (e.g., VX nerve gas exposure).
Where are acetylcholine receptors concentrated in the NMJ?
They are located at the top third of the junctional folds, as shown by radioactive bungarotoxin labeling.
What triggers neurotransmitter release at the presynaptic terminal?
Ca2+ influx at active zones triggers vesicle fusion and neurotransmitter release.`
What are the steps of the synaptic vesicle cycle?
Vesicle filling, docking at the active zone, ATP-dependent priming, fusion upon Ca2+ influx, and recycling via endocytosis.
What is the function of synaptotagmin?
A synaptic vesicle protein that binds Ca2+ and triggers vesicle fusion with the plasma membrane.
What is the SNARE complex?
A three-protein complex (Synaptobrevin, Syntaxin, SNAP-25) that brings synaptic vesicles into close proximity with the presynaptic membrane for fusion.
How does the SNARE complex drive vesicle fusion?
It forms a four-helix bundle, bringing vesicles close to the membrane, allowing rapid Ca2+-triggered fusion.
What is the role of Munc18 in the SNARE complex?
Munc18 binds the SNARE complex to regulate vesicle docking and fusion, preventing spontaneous neurotransmitter release.
How do botulinum and tetanus toxins affect the SNARE complex?
They cleave SNARE proteins, preventing synaptic vesicle fusion and leading to paralysis.
What are the three main mechanisms of synaptic vesicle endocytosis?
Kiss-and-run (fastest), clathrin-mediated (moderate), and bulk retrieval (slowest, occurs under high activity).
What is the active zone?
A specialized presynaptic region where synaptic vesicles dock and fuse, aligned with postsynaptic receptors for efficient neurotransmission.
What are the key functions of the active zone?
Vesicle docking/priming, stabilizing Ca2+ channels, coordinating alignment with the postsynaptic cell, and modulating plasticity.
What are the core proteins of the active zone?
RIM, Unc13/Munc13, RIM-BP, Liprin-alpha, and ELKS, which form a scaffold for synaptic vesicle fusion.
How does RIM contribute to the active zone?
Recruits and stabilizes Ca2+ channels, aids vesicle docking, and regulates short-term synaptic plasticity.
What is the function of RIM-BP?
Links RIM to Ca2+ channels, stabilizing their positioning for efficient neurotransmitter release.
What is the function of Munc13?
Primes SNARE proteins for vesicle fusion and helps regulate short-term synaptic plasticity.
What does Liprin-alpha do in the active zone?
Helps position active zones and establish synaptic contact sites.
What is the role of ELKS in the active zone?
Anchors calcium channels and regulates the number of primed vesicles at the release site.
How is synaptic vesicle fusion aligned with postsynaptic receptors?
Trans-synaptic adhesion proteins and retrograde signaling ensure precise alignment for efficient transmission.
What is the role of synaptic vesicles in synaptic transmission?
They store neurotransmitters and release them upon fusion with the presynaptic membrane in response to Ca2+ influx.
What is the relationship between the SNARE complex and synaptotagmin?
SNARE complex facilitates docking and fusion, while synaptotagmin acts as the Ca2+ sensor to trigger rapid fusion.
What is the function of NSF and SNAP in vesicle fusion?
NSF and SNAP use ATP to dissociate the SNARE complex after fusion, enabling the cycle to restart.
What is in SNARE and what is it for?
SNARE is for SV Fusion
includes synaptobrevin, SNAP-25, and syntaxin
Synaptic Vesicle Cycle?
Vesicles w/ NT -> dock at Active Zone -> ATP-dependent priming-> Ca2+ influx and fusing -> recylced via clathrin-dependent endocytosis
