Week 10 (Memories, LTP,

Memories

Behaviorally rehearsal is needed for short-term memory to be consolidated into long-term memory

Anatomically when one neuron repeatedly stimulated another the connection is strengthened

Through a process called long term potentiation or LTP

Donald Hebb

Proposed a neural mechanism for change at a synapse in response to learning

When the axon of neuron A repeatedly takes part in firing neuron B some changes occur in one or both cells such that A is better able to stimulate B in the future

• Cells that fire together, wire together

LTP

Strengthening of synapses due to repeated bursts of stimulation between two or more neurons

• one or more axons connected to a dendrite repeatedly and quickly stimulate that dendrite

• This burst of stimulation leaves some of the synapses potentiated

• The postsynaptic cell will be more responsive to the same type of stimulation

This process can last for minutes, days, weeks, or even longer

Is thought to underlie the neural mechanism for memory

• 3 main properties of LTP

  • Specificity - only highly active synapses on a cell become strengthened

  • Cooperativity - nearly simultaneous stimulation of 2 or more axons is more effective in producing LTP than stimulation from only one axon

  • Associativity - Pairing a weak input with a strong input eventually enhances the weaker input

• These properties all reflect what we would expect if memory has a cellular basis

Hippocampus

LTP is most consistently examined in the hippocampus

• LTP is easy and consistent to demonstrate

• Has been extensively studied

• The hippocampus is important for many aspects of memory

• One of the main regions we examine LTP is at the Schaffer collateral pathway

  • Includes axons from the CA3 pyramidal cells to CA1 postsynaptic targets

• Most synapses in the hippocampus involve glutamatergic receptors

Two Main Types of Receptors

• NMDA

  • Responds to glutamate and NMDA

  • are initially blocked by a magnesium ion

  • Needs the binding of glutamate plus the cell membrane needs to be depolarized for the ion channels to open

  • If these conditions are met then the calcium and sodium will enter the cell

  • Calcium entry is key to maintaining LTP

  • Only high levels of activity will lead to openining

• AMPA

  • Responds to glutamate and AMPA

  • Automatically open the ion channels once glutamate binds to them

  • Leads to sodium influc

• There are both ionotropic receptors named after the drugs they respond to

• For LTP to occur both types of receptors need to be activated

• Membrane depolarization + glutamate binding leads to activation of both AMPARs and NMDARs

Postsynaptic and Presynaptic Changes during LTP

Postsynaptic effects of LTP

• LTP can lead to long-lasting effects on the postsynaptic cell

  • Building of more AMPARs

  • Increased dendritic spines and branches

  • AMPARs become more responsive to glutamate

  • Building of more NMDARs

Presynaptic changes during LTP

• Continued stimulation of the postsynaptic neuron leads to release of a retrograde transmitter that goes to the presynaptic neuron

• Most common retrograde transmitter is nitric oxide

  • Decrease threshold needed for producing an action potential (makes it easier to depolarize)

  • Increases release of neurotransmitter

  • Expands axon

  • Releases neurotransmitter from additional sites along the axon

Long Term Depression (LTD)

There needs to be a balance in the brain in response to new information/stimulation

• otherwise every time you learned something new your brain would keep being more and more active

• This would require too much energy

As a possible compensation to LTP when one synapse is strengthened another is weakened

• called LTD

LTD is a prolonged decrease in response at a synapse when axons have been less active than others