Longterm Potentiation

1. Longterm Potentiation COGS 551 Human Memory Spring semester 2007 METU Annette Hohenberger

2. Longterm Potentiation � Synaptic Plasticity Learning and Memory involves synaptic plasticity Synaptic plasticity is brought about by changes in the structure and/or in the biochemistry of the synapses

3. Longterm potentiation LTP �LTP is a long-lasting enhancement of synaptic transmission in response to brief, high-frequency stimulation of presynaptic neurons.� (Wixted 2004:259) LTP has been studied intensively in the hippocampus (part of the limbic system) Intense electrical stimulation of axons which lead from entorhinal cortex to the dentate gyrus gives rise to longterm stronger synaptic excitatory potentials in the postsynaptic neuron.

4. The hippocampusas part of the limbic system

5. Hippocampus

6. The hyppocampus and related areas

8. Before we look at the biochemistry of LTP, let's do a short Neuroscientific rehearsal-- A synapse-- Synaptice vesicles

9. 2 mechanisms of synaptic plasticity 1. Biochemical change: Strengthening of individual synapses through the increase in postsynaptic non-NMPA (AMPA) receptors. With more AMPA receptors present, the release of glutamate by the terminal buttons causes a larger postsynaptic potential) 2. Morphological/structural change: new synapses are formed

10. 1.Strenthening of individual synapsesRole of NMDA receptors in LTP LTP happens when electrical impulses are fired successively at a high rate so that the postsynaptic neuron is depolarized LTP involves a special kind of receptor � the NMDA receptor and a special kind of transmitter � glutamate

11. The biochemistry of LPT � NMDA receptors NMDA = N-methyl-D-aspartate. That is the name of the drug that specifically activates it. The NMDA receptor controls a calcium ion channel whichis normally blocked by a magnesium ion Mg2+. When the postsynaptic membrane is depolarized, the Mg2+ ion is ejected and the glutamate molecule can open the ion channel so that Calcium Ca2+ ions can enter it. This process takes place in the dendritic spine.

12. The NMDA and non NMDA receptors The ion channel only opens when the postsynaptic membrane is depolarized AND when gluatamate is present The postsynaptic membrane gets depolarized through another receptor, a non-NMDA receptor (AMPA receptor). Glutmate activates this non-NMDA receptor upon which it lets sodium (Na) in which depolarizes the postsynaptic membrane AMPA = a-Amino-3-hydroxy-5-methyl-4-isoxazole-propione acid Drugs that block the NMDA receptor prevent LTP

13. Role of glutamate in NMDA and nonNMDA (AMPA) receptors

14. NMDA and nonNMDA receptors

15. NMDA and NonNMDA receptors

16. The mechanism of LTP - NMDA An action potential in the axon of a presynaptic neuron reaches the dendrite of a postsynaptic cell and causes its depolarization. An action potential runs down the axon of the postsynaptic cell The depolarization wave also floods back into the synapse of the dendrites. All synapses active at this moment, even those that are only weakly activated, are primed through this flooding back and calcium enters the NMDA receptor cells.

17. 2nd mechanism of synaptic placticity:growth of novel synapses Before LTP, there is one active zone of the postsynaptic density in the dendritic spike of the postsynaptic neuron. The postsynaptic density is a dark band in the postsynaptic membrane consisting of various proteins and enzymes. After LTP, the postsynaptic neuron projects a spike which reaches into the terminal button of the pre-synaptic neuron. Its postsynaptic density looks perforated then.

18. The postsynaptic density The postsynaptic membrane is characterized by a typical thickening, the postsynaptic density (PSD), carrying the neurotransmitter reception apparatus.

19. Formation of new synapses - Synaptogenesis The perforation of the postsynaptic density is only the first step that leads to a division of the terminal end button of the pre-synaptic and of the dendritic spine of the postsynaptic neuron After LTP, the number of synapses has grown

20. Formation of new synapses - Synaptogenesis

21. Short animations on LTP

22. Longterm depression LTD Learning goes both ways: The opposite process of LTP is Longterm depression, LTD. LTD also works via NMDA receptors. It leads to the weakening of synapses and a decrease in AMPA receptors

23. LTP vs. LTD LTP New sensory input becomes firmly learned and memorized in the long term A concurrent input that is correlated with a strong input is strengthened --> Classical conditioning, associative learning LTD Learned input fades --> forgetting A concurrent input that is not correlated with a strong input is weakened Concurrent input that is correlated with non-activation of the postsynaptic neuron is weakened, as in weak depolarization or hyperpolarization

25. Other forms of LTP LTP has been predominantly studied in the hippocampus. However, it occurs in other parts of the brain also: PFC, motor cortex, visual cortex, etc. There exists LTP without NMDA receptors, however, little is known about these processes.

26. Range of LTP LTP occurs on the range of a few hours over a couple of days to weeks . It is, however, NOT the way in which memories are permanently stored (Wixted 2004:259)

27. Hightened level of activation through LTP

28. References Carlson, Neil R. (2004): Physiology of behavior. Boston: Pearson Education, Inc. Chapter 13: Learning and memory. Basic Mechanisms, 410-450. Wixted, Joh (2004): The psychology and neuroscience of forgetting. Annu. Rev. Psychol. 55, 235-269.