NEUS 609 - Synapse formation

spatial distribution

___ of synaptic transmission is consequential

• excitatory dendritic spine synapses are farther from axon hillock, thus need more input to trigger depolarization

• inhibitory dendritic and somatic synapses are closer to axon hillock, thus need less signal to inhibit action potential

basket cells

type of GABAergic interneuron with highly branched axonal arborizations around another neuron’s cell soma.

asymmetrical

chemical synapses are ___ meaning that the transmission is UNIDIRECTIONAL

• there are vesicles in presynaptic membrane

• NO vesicle in postsynaptic membrane

steps of synapse formation

1. recognition (SynCAM, neurexin, neuroligin)

2. induction

   1. differentiation (neurexin, neuroligin, cadherins)

recognition molecules

___ make sure that the growth cone is on the right spot on the target cell.

neurexin

recognition molecule expressed on presynaptic membrane

• transmembrane protein inducing synapse formation and assembly

• cytoplasmic domain recruit and stabilize presynaptic components

neuroligin

recognition molecule expressed on the postsynaptic membrane

• transmembrane protein that induces synapse formation and assembly

• cytoplasmic domain recruit and stabilize postsynaptic components

heterophilic binding

binding of an adhesion molecule in one cell to a non‐identical adhesion molecule in an adjacent cell.

• neurexin and neuroligin express ___

growth cone

when talking about neurexin, we are still talking about the ___ because the synapse has yet to be formed

synapse

When neuroligin and neurexin bind, keeping both cells close but apart, the ___ is formed

• stabilize synaptic cleft and forces/trigger presynaptic specification and vesicle formation.

active zone

presynaptic structure

site where vesicles can bond and fuse with the membrane to release neurotransmitter before being recycled.

• kind of a launching pad for vesicles

postsynaptic density

aka PSD

postsynaptic structure

zone packed with receptors and scaffolding proteins whose formation is responsive to presynaptic signaling

rapidely

active sone forms __ from vesicle packets that are pre-assembled in the cell body and transported down the axon to the presynaptic terminal

slowly

PSD forms ___ by accumulation of proteins synthesized by postsynaptic cell

• some are synthesized locally in the dendrite, but most of it come from cell body

neuroligin 2

recognition molecule expressed on postsynaptic cells to form inhibitory synapses

• tend to be found directly on dendrites or closer to cell soma

• NEVER on dendritic spine

neuroligin 1/3

recognition molecule expressed in postsynaptic cell to form excitatory synapses

• ONLY on dendritic spines

PSD 95

primary organizer molecule at excitatory synapses

• forms filaments that bind to NMDA and AMPA receptors, potassium K+ channels, and scaffolding proteins to stabilize PSD complex.

• protein scaffold/PSD complex anchored to microfilament/actin to regulate the DYNAMIC morphology changes of dendritic spines

Gephyrin

primary organizer molecule at inhibitory synapses

• recruits inhibitory synapse-specific proteins like GABA and glycine receptors

• anchors mostly in microtubules some actin still present

• less protein density makes inhibitory synapse faster

excitatory synapses

• organized by neuroligin 1/3

• scaffold protein PSD 95

• NMDA, AMPA receptors

• microfilament/actin skeleton

inhibitory synapses

• organized by neuroligin 2

• scaffold protein gephyrin

• GABA, glycine receptors

• microtubules & microfilaments

autism

mutations in Shank and synGAP lead to serious ___

pruning, disuse

at least HALF of synapsed generated within the first two years of life are eliminated by ___ and ___.

• mostly excitatory synapses as it concerns dendritic spines

refinement

synapses pruning and elimination lead to ___ of neural circuitry

• mostly affect synapses on dendritic spines (excitatory)

step of synapse elemination

1. spinogenesis (new dendritic spines in early development)

2. spine pruning (based on activity)

3. Maintenace (low level genesis and pruning based on activity) 

22-25

pruning process is mostly over at around __-__ years of age