התפתחות סינפסות Synaptogenesis Illustrations from: Development of the Nervous System/ Sanes, Rea, Harris Golan H. 2010
נוירונים מייצרים חלק ניכר מאבני הבנין של הסינפסה לפני יצירת קשר עם נוירון אחר. מרגע יצירת המגע בין שני התאים סיגנלים תוך תאיים משרים את התמיינות הסינפסה החדשה. המאפיינים של סינפסה מייד עם היווצרה שונים במידה מסוימת מסינפסה בוגרת. נדרש זמן מה ל"התבגרותן" Golan H. 2010
Morphological evidences – detectable just in relative advance stage of synapse formation - EM. Golan H. 2010
Golan H. 2010
Golan H. 2010
Physiological evidences – Synapse function Golan H. 2010
Golan H. 2010
Golan H. 2010
Golan H. 2010
Synapse functional maturation: Presence of neurotransmitter synthesis and release machinery Before synaptogenesis. Neurotransmitter release – occur before synapse formation – Mechanism mostly vesicular. Golan H. 2010
Ca dependency Growth cone And Synapse (at all ages) Golan H. 2010
Adhesion Golan H. 2010
Golan H. 2010
Golan H. 2010
From growth cone to presynaptic terminal Neuroligin-1 b-Nerexin microtubules Vesicles frizzled Golan H. 2010
The elements of the PNS synapses Golan H. 2010
Innervation of muscle cell by the motor neuron induces: Increase in the number of receptors Increase in the amount of receptors clustering *Specificity Golan H. 2010
Neural Agrin or muscle Agrin Induces receptor clustering? Neural agrin induces Ach cluster. Use of Chick anti-Agrin that block (Function-blocking) the chick Agin. The clustering was blocked when the motor neuron was from Chick but not when the muscle was from Chick Golan H. 2010
Golan H. 2010 Neural Agrin induces Ach receptors phosphorylation: . When clusters are exposed to Agrin, MUSK – Agrin receptor is phosphorylated within minutes. And AChR are phsphorylated within an hours. Receptor aggregation ocure in a few hours, but the level of phosphorylation decline Golan H. 2010
Agrin binds to a receptor complex and MaSK is required for clustering Golan H. 2010
Golan H. 2010
The elements of the CNS synapses Golan H. 2010
EphB signaling influences Glutamate receptors aggregation In the CNS Golan H. 2010
Eph -Rs Golan H. 2010
White – glut application Yellow – size of synaptic currents Green – synaptic contacts Golan H. 2010
Neural activity Regulation of receptor expression Regulation of post and presynaptic transcription Synaptic strength Golan H. 2010
Activity dependent ….. Golan H. 2010 The activity dependent signal that supresses extrasynaptic receptors involve ca++ influx and activation of CamKII. Myogenin, a transcription factor in the muscle is phosphorylated and block transcription in extrasynaptic nuclei. When motor activity is blocked by TTX, myogenin is not active and extrasynaptic receptors cover the entire muscle Golan H. 2010
The duration of synaptic potentials decreases during development Central auditory nucleus. LSO- lateral superior olive MNTB – medial nucleus of the trapezoid body Golan H. 2010
Receptors subunits – regulation with age In all receptor types Depends on: Age Brain region Activity Chemiacl interactions (trophic factors) Golan H. 2010
Glutamatergic synapse maturation MNDA type glutamate receptors close more rapidly with age. The recordings were done while GABA a AMPA receptors were blocked Golan H. 2010
Golan H. 2010
Golan H. 2010
YFP- dendritic spine - green Murai et al, 2003 Eph A3 on astrocyte – red Synaptophysin – blue YFP- dendritic spine - green A role of astrocyte in The regulation of spine shape Golan H. 2010