BISC 421 1st Edition Lecture 37 Outline of Current LectureI. Development ContinuedCurrent LectureDevelopment ContinuedNeurotrophin and receptor family4 ligands!3 receptors (p75 is common to all)•There are other growth factors shown here that each bind to a receptor •For test: name one growth factor •For MC choose the one she talks about the most for the testDifferent target neurons respond to different neurotrophins!•The reason we have multiple growth factors is for more specifcity – diferent target neurons respond to diferent neurotrophins •They each have receptors for diferent types of growth factorsNMJ! Synapse elimination – 1 motor neuron/muscle fber" Elaboration of the synapse "Clustering of AchR in the muscle at the postsynaptic site"•How are our synapses formed?•Somewhat poorly understood•Formation between the muscle and the motor neurons (system that is best understood)•How do we have one nerve fber innervating one muscle fberSynapse formation: NMJ!•At birth the muscle fbers are innervated by many neurons•Then as we mature only a single neuron innervates a muscle fiberNeurons can be visualized in brainbow mouse!Pruning at the nmProcess of pruning can be visualized – here two neurons labeled with different colors are followed over time. Green is the winner! Blue retracts. The factors that determine who wins are not known, but once a cell is innervated a muscle fber, it cannot innervate another muscle fbers. (Red shows site of synapse)•How does a cell know that a cell is already innervating a muscle fiber •Brainbow because the neurons are all labeled in diferent colors-‐ what it does is allow the investigator to follow single neurons and watch the path fnding of the growth cone and how synapses are eliminated at the NMJ•Initially cell is innervated by 2 diferent axons – initially the blue cell looks like it is occupying the most territory-‐ but in this case we see this cell retracting and forming a ball and leavingElaboration of the synapse• Reach myotube• Touch and stop• Pre: differentiation of presynaptic terminal starts• Post: cluster ACh receptors• Post: increase Ach receptor number• Polyneuronal innervation• Pre and postsynaptic specializations completed• Loss of polyneuronal innervation•This process is well understood•Alignment of the post synaptic cell (muscle) with pre synaptic cell•How do they communicate?•This process can be described here (don't need to memorize all of these steps)•Increase of Ach receptors in muscle fber when nerve touches it-‐•Increases Ach receptors and gene expressionPostsynaptic changes•Focus on this: redistribution of Ach receptors and increase in expression of ACh receptors (increase at synapse and decrease at other sites)•In adult only have Ach receptors in post synaptic cell•Each nuclei can transcribe diferent genes•A molecule was identifed for clustering-‐ agrin•Motor neuron releases agrin at site of synapse causing ACh receptors to cluster•Muscle cells have receptor for agrin•Highly expressed gene in muscle called MUSK•This receptor is acting to increase activity of a molecule that physically reacts with ACh receptors and holds them togetherNeuregulin (ARIA) increases synthesisBrain extract added to muscle: increase ACh receptor synthesis!Purify from brain: ARIA (Acetylcholine receptor inducing activity) = neuregul• Nerve makes neuregulin!• Receptors = ErbB2 (B3, B4)!• Signal to nucleus induces expresionof AchR•Increase in Ach receptors gene expression due to ARIA•This receptor signals to the
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