Synapse Formation
What happens when growth cones that come in contact with an appropriate post synaptic cell? (6 things)
1. They lose their filopodia 2. small adherens junctions form between the cells 3. coated vesicles appear on both sides 4. synaptic vesicles accumulate on the presynaptic side 5. the synaptic density forms on the postsynaptic side 6. ECM (extracellular matrix) appears in the synaptic cleft
How many vesicles are needed to establish a functional presynaptic terminal?
2-3
Receptor clustering (NMJ) is evident ___ after contact
3 hours
In the spinal cord ____% of the synapses form on dendritic growth cones
75
The presynaptic terminal contains 2 main elements: ____ and ____
Synaptic vesicles containing neurotransmitter and the presynaptic density
Presynaptic vesicles contain:
Synaptobrevin (vesicle fusion), neurexins, cytoskeleton-associated proteins, calcium channels
Growth cones slow when they enter the target cell population. Neurons in the ____ initiate the slowing
Target
Synapses mature ____ and ____ over time
structurally and functionally
Signaling between the pre and post synaptic cells induces ____
synapse formation
Neurons prepare for ___ well before contact is made between cells
synaptogenesis
____ isoforms are present during CNS clustering
MuSK
Agrin initiates phosphorylation of ____, which phosphorylates AChR subunits. Phosphorylated AChR subunits bind ____, which clusters AChRs.
MuSK, Rapsyn
An autoimmune disease with severe muscle weakness due to poor NMJ communication. Patients have antibodies to AChR or MuSK.
Myasthenia Gravis
____ is an ECM protein in the glutamatergic clefts. It appears to be required for AMPAr clustering
Narp
As CNS synapses mature, ____ are expressed by some neurons and released at synapses.
Neuregulins
3 genes code for this, each with an Alpha and Beta form.
Neurexin
Cleft proteins involved in adhesion (4)
Neurexin Neuroligin Cadherins Protocadherins
5 genes code for this. The 1,3, and 4 variants are in excitatory synapses, and the 2 variant is in inhibitory synapses.
Neuroligin
The postsynaptic element contains ___ and ____
Neurotransmitter receptors and the postsynaptic density
Excitatory neurotransmitter at sympathetic synapses
Noradrenalin
Axons cannot have action potentials before they form synapses. True or False?
False, though synapse formations and activity are required for full electrical maturation
Main inhibitory neurotransmitter in the CNS
GABA
Excitatory neurotransmitter at neuromuscular and parasympathetic synapses
Acetylcholine
Four ____ splice variants are also expressed in the brain. They may be important for CNS clustering
Agrin
___, an ECM molecule released by the motor neuron axon at the NMJ, initiates clustering
Agrin
Gabapentin, a common analgesic and anti-epileptic drug, blocks the ____ receptor.
Alpha-2/Gamma-1
Synapses are often surrounded by ____. They remove and recycle neurotransmitter, insulate synapses from each other, and regulate extracellular ionic environment
Astrocytes
Main excitatory neurotransmitter in the CNS
Glutamate
Neuron Slowing EX: Pontine neurons grow rapidly on cerebellar glial cells, but slowly on cerebellar granule cells. Contact between the growth cone and ____ are required for slowing
Granule cells
Presynaptic proteins appear at the site of contact ___ after contact. Postsynaptic proteins appear ___.
One hour, slightly later
Poststynaptic proteins involved in anchoring (2)
PSD93 PSD95
Synapses develop ____ before anatomically. We know this because ____
Physioligically, growth cones can release neurotransmitter, growing axons can have APs
____ are neuregulin receptors, and are tyrosine kinases that activate CREB via the MAPK pathway.
erbBs
Presynaptic proteins for vesicle fusion (4)
piccolo bassoon rim SNAP25
The number of synapses on a neuron varies from ____ to ____
1 to 10000
Astrocytes are required for synapse maturation in the CNS. Give 2 reasons.
1. Cholesterol from astrocytes promotes maturation. 2. Thrombospondin from astrocytes activate Alpha-2/Gamma-1, which is required for excitatory synapse formation.
Rapsyn anchors the ____ and dystroglycan, it is required for AChR clustering
AChR
Neurotrophin, particularly ____ in the CNS, increase synapse maturation and number.
BDNF
____ activation increases expression of neurotransmitter receptor
CREB
In an adherens junctions, which cell adhesion molecules are involved?
Cadherins, protocadherins, SynCAMs, Nectins, Many other CAMs
Most communication between a neuron and target cells is via a ____ synapse
Chemical
Presynaptic proteins for vesicle recycling (1)
Dyamin
Action potentials become shorter with age (frog Rohan-Beard cells). Why is this?
Early APs: Voltage gated potassium. Later APs: Voltage gated sodium, Final APs: voltage gated potassium add a delayed rectifier function
The density of ion channels does what as the cell matures?
Increases
Low Density lipoprotein receptor-related protein 4 (LRP4) in the muscle binds ____
MuSK
What are the 3 structural elements of a synapse?
Presynaptic terminal, synaptic cleft, postsynaptic element
____ is an ECM glycoprotein in the basal lamia of the NMJ. It anchors the axon termal and drstroglycan
S-Lamanin
Presynaptic proteins (vesicle proteins, 3)
Snyaptophysin Synaptotagmin Synaptobrevin (VAMP)
Misexpression of neuroligin-1 in non-neurons can initiate presynaptic cell differentiation with neurons that contact it. What would you expect to happen if neuroligin-coated beads were in contact with neurons in culture?
a clustering of presynaptic proteins
Nuclei ___ at the NMJ, and transcription for ____ is elevated in these nuclei.
accumulate, AChR
In the CNS, ____ and ____ initiate clustering of their receptors specifically
glutamate, GABA
Calcium levels ____ immediately after contact with an appropriate postsynaptic cell
increase
Expression of NT receptor increases as synapses ____
mature
As development progresses, resting membrane potential of neurons becomes more... (positive, negative, neutral)
negative, partly due to glia regulating extracellular potassium (35mM to 3mM)
In the mature synapse, adhesion in the active zone is mediated presynaptically by ____ and postsynaptically by ____.
neurexin, neuroligin ex. Neuroligin binds PSD95 (scaffolding protein) and PSD95 binds neurotransmitter receptor proteins
Mutations in this protein group have been found schizophrenia, autism, and mental retardation. leading the the hypothesis that synaptic structure/function may be involved in these conditions.
neuroligin
Synaptic communication requires release of ___ from ___ to ___ on ___
neurotransmitters from presynaptic cells to receptors on postsynaptic cells
Muscle Specific Kinase (MuSK) is a receptor tyrosine kinase found in the NMJ. Knockouts show no ____
receptor clustering