Lecture 11 Flashcards
Neurophysiology
What are the steps of synaptic transmission?
- Presynaptic action potential arrives at the terminal.
- Calcium influx triggers vesicle fusion.
- Neurotransmitters released into synaptic cleft.
- Postsynaptic receptors respond to neurotransmitters:
Glutamate → Excitatory (depolarization).
GABA → Inhibitory (hyperpolarization). - Signal is terminated by reuptake, breakdown, or diffusion.
What does ‘correlation between structure and function’ mean?
The size of the dendritic spines (structure) correlates to the amount of receptors in the synapse (function). The larger the structure, the more sodium passing to glutamate receptors, the more efficient it will depolarize the post-synpatic cell and the more efficient synaptic transmission will occur.
What is synaptic transmission?
Synaptic transmission is the process by which a signal is passed from one neuron to another across a synapse.
What determines the size of dendritic spines?
Rho GTPases: there are 20 different ones but most important: PhoA, Rac1 and Cdc42
They are like molecular switches -> either on or off.
When on, they signal (polarize/depolarize) to actin cytoskeleton.
How many dendritic spines does a neuron have?
ten thousands, depending on type of neuron even more
What is the role of actin in the dendritic spines?
Its the primary cytoskeletal element. It provides structural support and enables the dynamic remodeling of spines during synaptic plasticity, learning, and memory.
What are Rho GTP and Rho GDP?
They are part of the Rho GTPases cycle, they sense changes in signalling and translate that to changes in actin. When switches bind GDP they are off (no actin) when bind to GTP they are on (actin).
When do dendritic spines change?
Changes during development but also when learning (synaptic plasticity). Can change within minutes.
Just before and after birth you generate a lot, during puberty you eliminate the ones that are not used (pruning), in adulthood spines stay stable but with aging you start losing.
What do dendritic spines have to do with neurodevelopmental disorders?
Often most prominent biomarker.
ASD/ID: spines genesis -> either too many or too little
SZ: too much elimination during pruning
Alzheimer’s/dementia: dramatic problem in last phase of life
–> almost all bain disorder have synapse or dendritic spine problems
What is synaptic plasticity?
Refers to the ability of the connections between already existing neurons to increase or decrease in strength.
What are LTP and LTD?
LTP: long term potentiation -> more glutamate receptors, likely trigger AP
LDP: long term depression -> less glutamate receptors, with same glutamate being released, will not trigger AP
–> can remain life-long
What does “cells that fire together, wire together” mean?
Whn cells fire at the same time, system assumes that they encode the same information and will make connection between them even more efficient.
What is the role of the NMDA receptor in LTP?
When its activated it passs calcium (others like AMPA pass sodium). This activates CaMKII which is a key molecule and necessary for memory and learning.
Why is the NMDA receptor also called the ‘coicidence receptor’?
When two cells fire AP exactly at same time, they are both depolarized. When post-synaptic cell is depolarized, magnetisum that sits in NMDA receptor gets kicked out, receptor will open, a lot of calcium will flow in. Can only happen when glutamate release and release of magnetisum happen at same time (both cells fire).
What happens if there is missense mutation which leads to no/little CaMKII?
Individuals are severely intellectual disabeled.
How does LTP work?
High-frequency stimulation → Strong glutamate release → Depolarization removes magnesium block from NMDA receptors → Calcium (Ca²⁺) enters postsynaptic neuron.
Calcium Signaling: Activates enzymes (e.g., CaMKII) → Increases AMPA receptor efficiency and adds new AMPA receptors.
Structural Changes: Dendritic spine growth reinforces the synapse.
Persistence: Protein synthesis maintains synaptic strengthening over time.
What is CaMKII?
Calcium/calmodulin-dependent protein kinase II, signalling pathway activated by calcium influx in post-synaptic neuron. Enhances the efficiency of existing AMPA receptors and promote the insertion of new AMPA receptors into the postsynaptic membrane.
How can you study LTP at single synapse level, in vitro?
You can cage glutamate and release it with light stimulation. At same time you can depolarize post-synaptic cell with 2-photon microscopy (can do very focal).
