1. Long Term Potentiation
LTP
Long Term Potentiation

2. Long Term Potentiation:
Potentiation: enhancement of one agent by another so that the combined effect is greater than the sum of the effects of each one alone.
In neuroscience, potentiation refers to the persistent strengthening of synapses based on recent patterns of activity.

3. Graph illustrates LTP. Notice the strength of EPSP after potentiation has occurred.

4. Synaptic Plasticity:
Ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.
Plasticity results from the alteration of the number of neurotransmitter receptors located on a synapse and neurotransmitter production.

5. Synaptic Plasticity:

6. Neurotransmitters:
Endogenous chemicals responsible for synaptic transmission.
Glutamate- (excitatory) plays a key role in LTP, memory, and learning.

7. Receptors:
AMPA (α-amino-3-hydroxy-5-methylisoxazole-4- propionic acid)
Receptor for glutamate
Allows influx of Na+ ions
Produces EPSP
NMDA (N-methyl d-aspartate)
Unblocked (opens) when neuron depolarizes
Allows rapid influx of Ca2+ ions

8. Ca2+ influence on LTP:
Rapid influx of Ca2+ into the postsynaptic neuron triggers the production of several protein kinases including CaMKII, PKC, PKA, and MAPK.
Protein kinases regulate cellular pathways; most importantly signal transduction.

9. CaMKII

10. Protein Kinase Influence on LTP:
Early LTP:
Increase activity of existing AMPA receptors
Insertion of additional AMPA receptors on postsynaptic membrane
Late LTP:
Initiates protein synthesis and gene expression
Increase dendritic spine number, surface area, and synthesis of AMPA receptors.

12. Retrograde Signaling:
Increases release of neurotransmitters by presynaptic neuron.
Requires message from postsynaptic neuron to presynaptic neuron (retrograde)
Messenger: nitric oxide

14. Hippocampus: Studies of LTP have involved the hippocampus.
Important structure of the brain involved in memory and learning.
Located along the medial surface of the brain.

16. Morris Water Maze:
1986 Richard Morris tested spatial memory of rats by pharmacologically modifying their hippocampus.
Rats with NMDA receptors blocked were significantly impaired.