Cellular Neurobiology BIPN140 Exam Depot Window...
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Cellular NeurobiologyBIPN140
1st Midterm Exam Ready for PickupBy the elevator on the 3rd Floor of Pacific Hall (waiver)
Exam Depot Window at the north entrance to Pacific Hall (no waiver)Mon-Fri, 10:00 AM to 4:00 PM
Regrade request is accepted till Nov 14th. Please contact the IA who graded the question directly.
Second midterm is next Tuesday!! Covers lectures 7-12 (Synaptic transmission, NT & receptors, intracellular signaling & synaptic plasticity).
Review session is on Monday (Nov 14th) before midterm 6:00-8:00 PM at 3500 Pacific Hall. Please come with questions.
PS 6 is now posted on the website2015 Problem sets #4~ #6 and 2nd midterm are also posted!
Chih-Ying’s Office Hour: Monday, 1:00-2:00 PM, Bonner Hall 4146
BIPN140 Lecture 13: Synapse Formation (Synaptogenesis)
Su (FA16)
1. Neuromuscular Junction (NMJ) Development
2. Synaptogenesis at Central Synapses
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Ultrastructural Image of an NMJ Active Zone
Basal Lamina
Junctional fold
Active zone
(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-7)
(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-7)
NMJ Develops in Sequential Stages (Fig. 23.11)
Immature:Multiple innervation
Mature:Monosynaptic innervation
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Post- (muscle fiber) => laminin => Presynaptic specialization
(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-9)
(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-11)
AChR clusters
Pre- (MN terminals) => Agrin => Postsynaptic AChR clustering
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(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-12)
Junctionalnucleus
Extra-junctional nucleus
neuregulin
A muscle fiber has multiple nuclei that can produce gene product independently.
Pre to post signaling: Neuregulin (+) and Ach (-)
Depolarization
Elimination of Multiple Innervation (Fig. 23.12)
Elimination of multiple innervation in the PNS. Live imaging of the same NMJ:
At P11, two axons (blue & green) innervate the same muscle. AChR labeled in red.
By P12, the proportion of territory occupied by the green and blue axons has begun to shift, with the green axon terminal expands.
By P14, the blue axon has fully retreated, its synaptic terminal transformed into a large retraction bulb then fully withdrawn from the synaptic site.
Motor neuron #1Motor neuron #2AChR
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Some Neuromuscular Synapses are Eliminated after Birth
Local blockade of AChR
Summary: NMJ Development
(Naguib et al., Anesthesiology 96, 202-231, 2002)
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Central v.s. NMJ Synaptogenesis
(Kandel et al., Principles of Neural Science, 5th Edition, Fig 55-14)
NMJExcitatory
Central Synapse
Inhibitory Central
Synapse
Dendritic Spine Dendritic Shaft
Axon VaricosityAxon Varicosity
Presynaptic bouton: small axonal varicosities, ~1 m in size, establishing contacts with postsynaptic cells.
Active zone: presynaptic region where SV fusion can occur (visible in EM as a meshwork of proteins).
Postsynaptic density: opposing the active zone, clusters of NT receptors, channels, signaling molecules & scaffolding proteins.
Signaling Pathways Regulating CNS Synaptogenesis
(Waites, Craig & Garner, Annu Rev Neurosci, 2005)
Axo-dendritic synapse
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Cell Adhesion Molecules Guiding Synaptic Specificity (23.4 & 8)
Potential Molecular Mediators of Synapse Identity (Fig. 23.9)
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Inductive Factors for Synaptogenesis (Fig. 23.8)
Neurexin (pre-)-Neuroligin (post) Interaction Promotes Synaptic Differentiation
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Ephrins and Eph Receptors (Fig. 23.4)
1. Filopodium extends from dendrite
2. Initial contact with axon terminal/branch (adhesive factors).
3. Inductive events: specific trans-synaptic acting components.
4. Maturation (asymmetric): (a) presynaptic active zones (b) postsynaptic scaffolds: clustering of receptors, segregated
receptor distribution, signaling molecules, ion channels, cytoskeletal reorganization, etc.
(c) increased NT release and receptor responsiveness
Developmental Sequence of Glutamatergic Synapses
Axo-dendritic synapse
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Fig. 1. Exposure of mice to increased circuit activity reveals an NPAS4-depdendent regulation of inhibition in vivo.
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Fig. 2. Behaviorally induced NPAS4 differentially regulates inhibitory synapse function across the somato-dendritic axis of pyramidal neurons.