Cellular Neurobiology BIPN140 1st Midterm Exam Ready for Pickup By the elevator on the 3 rd 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 14 th. 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 14 th ) before midterm 6:00-8:00 PM at 3500 Pacific Hall. Please come with questions. PS 6 is now posted on the website 2015 Problem sets #4~ #6 and 2 nd midterm are also posted! Chih-Ying s Office Hour: Monday, 1:00-2:00 PM, Bonner Hall 4146 BIPN140 Lecture 13: Synapse Formation (Synaptogenesis) 1. Neuromuscular Junction (NMJ) Development 2. Synaptogenesis at Central Synapses Su (FA16)
Ultrastructural Image of an NMJ Active Zone Basal Lamina Active zone Junctional fold (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-7) NMJ Develops in Sequential Stages (Fig. 23.11) Immature: Multiple innervation Mature: Monosynaptic innervation (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-7)
Post- (muscle fiber) => laminin => Presynaptic specialization (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-9) Pre- (MN terminals) => Agrin => Postsynaptic AChR clustering AChR clusters (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-11)
Pre to post signaling: Neuregulin (+) and Ach (-) Junctional nucleus neuregulin Extra-junctional nucleus Depolarization A muscle fiber has multiple nuclei that can produce gene product independently. (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-12) Elimination of Multiple Innervation (Fig. 23.12) Motor neuron #1 Motor neuron #2 AChR 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 By P14, the blue axon has fully retreated, its synaptic terminal transformed into a large retraction bulb then fully withdrawn from the synaptic site.
Some Neuromuscular Synapses are Eliminated after Birth Local blockade of AChR Summary: NMJ Development (Naguib et al., Anesthesiology 96, 202-231, 2002)
Central v.s. NMJ Synaptogenesis NMJ Excitatory Central Synapse Axon Varicosity Inhibitory Central Synapse Axon Varicosity Presynaptic bouton: small axonal varicosities, ~1 m in size, establishing contacts with postsynaptic cells. Dendritic Spine Dendritic Shaft 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. (Kandel et al., Principles of Neural Science, 5 th Edition, Fig 55-14) Signaling Pathways Regulating CNS Synaptogenesis Axo-dendritic synapse (Waites, Craig & Garner, Annu Rev Neurosci, 2005)
Cell Adhesion Molecules Guiding Synaptic Specificity (23.4 & 8) Potential Molecular Mediators of Synapse Identity (Fig. 23.9)
Inductive Factors for Synaptogenesis (Fig. 23.8) Neurexin (pre-)-neuroligin (post) Interaction Promotes Synaptic Differentiation
Ephrins and Eph Receptors (Fig. 23.4) Developmental Sequence of Glutamatergic Synapses Axo-dendritic synapse 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
Fig. 1. Exposure of mice to increased circuit activity reveals an NPAS4-depdendent regulation of inhibition in vivo.
Fig. 2. Behaviorally induced NPAS4 differentially regulates inhibitory synapse function across the somato-dendritic axis of pyramidal neurons.