L9- Long-Term Potentiation (& depression)

I am in 13th grade.

Long-Term Potentiation (LTP)

long-term increase in excitability of a neuron to particular synaptic input, caused by repeated high-frequency activity @ particular synapse

LTP proving Hebb’s Rule

1. dramatically stimulated PP axons (prefrontal/excite pathway) from entorhinal cortex to dentate gyrus

2. recorded extracellular space in denate gyrus

3. detected excitatory postsynaptic potentials (ESPSs) in denate gyrus

LTP Process

neurons let cations in, extracellular space outside grows; w/ time, u have stronger & stronger dips

• only if many axons stimulated rapidly, EPSPs produced by terminal buttons will summate & postsynaptic mem will depolarize enough for LTP to occur

  • if axons added slowly: ESPSs won’t summate add/build on each other & LTP won’t occur

• back to back to back

• change seen after exceeds threshold of establishment of LTP

Glutamate in LTP

LTP is more likely to occur w/ coincidence of presynaptic- postsynaptic activation need both responding/activation

• NMDAr capable of doing both

  • presynaptic was activated so Glu came from somewhere when this leaves, NA is let in & this leads to voltage change

• NMDAr is an ionotropic Glu receptor that contain CA² ion channel; also contains voltage-dependent Mg² ion block only removed & Ca² let in

How Glutamate in LTP Works

1. depolarized presynaptic neuron releases Glu

2. Glu binds to postsynaptic AMPAr & NMDAr

3. Glu binding to postsynaptic AMPAr opens its corresponding Na channel

4. With enough AMPAr activity, the postsynaptic neuron depolarizes

5. Depolarization (& glycine binding) liberates Mg² ion block

6. Ca² ion channels on NMDAr open, permitting CA² influx

Calcium in LTP

Ca² imp for postsynaptic processes

1. Ca² binds to/activated enzyme CAM-KII

   • makes stuff happen

2. Activated CAM-KII triggers cascade of signaling

   • impact: inc of AMPAr in dendritic buttons

3. Signaling cascade promotes translocation of AMPAr to the synapse

   • lets in Na ions which depolarize cell

4. Increased CAM-KII activity contributes to increased dendritic spike diameter & stability

Blockade of NMDAr-induced Ca² influc prevents LTP

Dendritic Spikes

• backpropagation: process involved in rtaining a neural network, fine-tunes

• backpropagation of an AP from axon hillock across cell body dendritic membranes

  • only in certain neurons (pyramidal cells)

• when pyramidal cells fire an axonal AP, all its dendritic spikes depolarize for brief time

  • easier for neurons to allow Na response

Long-Term Depression

opp of LTP, happens all the time but less often

• repeated low-frequency weak stimulation of a synaptic input decreases strength

1. continuous presynaptic Glu release only causes few depolarizations

2. only lets in small amount of Ca² (<5nM) of postsynaptically

3. reduced Ca² influx affects different groups of Ca- dependent enzymes

4. activated AMPAr expression decreases postsynaptic response to Glu

-amount of Ca² makes the diff