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