2 Long Term Potentiation

Question 1

What is Hebbian learning?

Answer 1

• CS has a weak synapse compared to US innate, hard-wired synapses
• CS synapses are strengthened when it is active in close time with US synapse
• Over time, CS produces UR

“Neurons that fire together, wire together”

Question 2

What is LTP?

Answer 2

Long term potentiation is a physiological example of synaptic plasticity and a change dependant on experience.

Question 3

What are LTP experiments commonly done on?

What are the pathways?

Answer 3

Experiments are often done on the hippocampus in vivo.

The 3 pathways are:

1. Entorhinal cortex -> project to detate gyrus
2. Dentate gyrus -> CA₃
3. CA₃ -> CA₁

Question 4

What are the experimental steps for the induction of LTP?

Answer 4

Baseline examination:

Record the baseline activity of dentate gyrus cells (post-synaptic neurons) whilst applying a low frequency stimulation to perforant path cells (presynaptic input).

1) Apply a high frequency stimulation to the perforant path cells. This leads to increased activation in dentate gyrus cells.
2) Apply the low frequency stimulation to perforant path cells again. Dentate gyrus cells show a higher response to that observed at baseline.

Question 5

What 3 properties of LTP?
Describe these properties

Answer 5

• Persistance: changes are enduring, lasting weeks
• Synaptic specificity: potentiation must only show in the synapses of the pre-stimulated cells. No increase senstivity in cells that weren’t involved
• Associativity: weak stimulation is paired with strong stimulation. Explained by Hebb’s model + “neurons that fire together, wire together”

(Answers part of “What properties make LTP a good model of the cellular basis of learning?”)

Question 6

What is the neurochemical basis of LTP?

Answer 6

(Hella long response. Be prepared)
LTP is dependent on the release of the excitatory neurotransmitter glutamate (Glu). Glu binds to 2 receptors:

• AMPA receptors
• NMDA receptors

Glu binding to AMPA receptors on the post-synaptic membrane causes immediate excitation of the post-synaptic neuron. This is not enough for LTP to occur tho.

Glu binding to NMDA receptors opens up Ca²⁺ channels, which are both ligand gated (need Glu to bind to NMDA receptor) and voltage gated (the post-synaptic neuron must be depolarised by Glu binding to AMPA). When these requirements are met, Mg²⁺ stops blocking the gate, Ca²⁺ flood in.

NMDA-receptor is responsible for the specificity and associativity that mediate LTP

A weak stimuli can jump in on this as it too releases glutamate. As the post-synaptic cell is already depolarised from the strong stimuli, Ca²⁺ channels on the NMDA receptors close to the weak stimuli are openned.
​-> Association

An intracellular cascade also occurs. Where an increase in post-synaptic nerve stimulation increases the number of AMPA receptors, so there is a higher cell response the next time.

Question 7

What are the examples of LTP and learning sharing a common mechanism?

Answer 7

• age-related decline in learning correlates with age-related decline in induction of LTP in hippocampus
• similar correlations between LTP and learning in mouse model of Alzheimer’s disease
• blocking NMDA receptors also produce learning deficits
  Learning a platform: Mutant mouse with NMDA receptor dysfuction vs. wild type mouse without mutation -> wild type mouse showed a stable and local growing pattern whilst mutant mouse pattern varied between sessions, showing no evidence that they had learnt the platform

Saturation of LTP effects learning:
- saturation of LTP in hippocampus can prevent rats from learning a simple maze

Question 8

What are the other types of learning related to plasticity?

Answer 8

• Long term depression
• Spine growth and other morphological changes
• Changes in glia - synaptic support, metabolic support, insulation and altered conductions speed. e.g. changes in mylination: more insulation, the faster the transmission speed.