lec 4 LTP

1. Long-term Potentiation Ruxandra Luca

2. The Cellular and Molecular Basis of Cognition

3. From Sidney Harris

7. “ Hebb’s Postulate”: When an axon of cell A … excites cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells so that A’s efficiency as one of the cells firing B is increased. D.O. Hebb, The Organization of Behavior , 1949.

9. TVP Bliss, FRS The discovery of LTP

10. In vivo recording from the rabbit hippocampus

11. The Entorhinal/Hippocampal System Entorhinal Cortex Dentate Gyrus CA3 Ipsilateral CA1 Perforant Pathway Mossy Fiber Schaffer Collaterals Stratum Lacunosom Molecular inputs Recurrent Connections

12. Bliss and Lomo’s First Published LTP Experiment No tetanic stimulation Tetanic stimulation High frequency synaptic stimulation, resulting in LTP

13. The Entorhinal/Hippocampal System Lateral Septum, Contralateral CA1 Entorhinal Cortex Dentate Gyrus CA3 Ipsilateral CA1 Perforant Pathway Mossy Fiber Entorhinal Cortex Subiculum Lateral Septum Amygdala, Cortex Schaffer Collaterals Norepinephrine, Acetylcholine, Serotonin GABAergic Interneuron CA1 Axon Schaffer Collaterals Stratum Lacunosom Molecular inputs Recurrent Connections SLM Inputs Dopamine,

14. The Dendritic Tree with a single axon passing through

15. The Dendritic Spines: thousands of contact points (synapses)

16. View of pre- & post-synaptic terminals DS = dendritic spine Sp = Synapse (postsynaptic terminal) AT = Axon (pre-synaptic) terminal Arrows indicate synaptic density

17. The Entorhinal/Hippocampal System Lateral Septum, Contralateral CA1 Entorhinal Cortex Dentate Gyrus CA3 Ipsilateral CA1 Perforant Pathway Mossy Fiber Entorhinal Cortex Subiculum Lateral Septum Amygdala, Cortex Schaffer Collaterals Norepinephrine, Acetylcholine, Serotonin GABAergic Interneuron CA1 Axon Schaffer Collaterals Stratum Lacunosom Molecular inputs Recurrent Connections SLM Inputs Dopamine,

18. Stimulating Electrode Recording Electrode Electrodes in a Living Hippocampal Slice

19. Tissue Slice Chamber

20. Stimulating Schaffer Collaterals in Area CA3 Recording in Stratum Pyramidale in Area CA1 Recording in Stratum Radiatum in Area CA1 Stimulus Artifact Fiber Volley EPSP Recording Configuration and Typical Responses in a Hippocampal Slice Recording Experiment Cell body layer Dendritic regions

21. B A An Input/Output Curve and a Typical LTP Experiment Delivery of 100 Hz synaptic stimulation

23. From Nicoll et al.

24. Malenka et al, Bear et al, Huganir et al. Low frequency stimulation induces Long-Term Depression (LTD)

25. Theta Pattern in Hippocampal EEG 1-voluntary movement 2-REM sleep 3-still-alert 4-slow-wave sleep Before and after a medial septal lesion.

27. Voltage Clamp Cell Body Stimulating and recording from a single neuron: pairing two stimuli Axon

28. Pairing two stimuli : Postsynaptic depolarization + presynaptic elctric pulse leads to LTP

30. Gly Glu + + + + - - - - - - - + + + Synaptic Glutamate Alone Cytoplasm Synaptic Cleft Mg ++ Ca ++ Glu Ca ++ + + + + - - - - Mg ++ Gly - - - + + + Glutamate plus Membrane Depolarization Cytoplasm Synaptic Cleft Ca ++ The NMDA Receptor is a coincidence detector

31. Experimental set up for the analysis of the associative nature of LTP

32. ASSOCIATIVE NATURE OF LTP German Barrionuevo and Tom Brown

33. Back Propagating Action Potential: From soma to dendrite stimulation recording recording Action potential K+ current

34. When postsynaptic depolarization precedes presynaptic neurotransmitter release synaptic depression occurs.

35. Pairing LTP TTX = tetrodotoxin (Na+ channel blocker inhibiting dendritic action potential)

36. NEURONAL INFORMATION PROCESSING

37. MOLECULAR MECHANISMS Graham Collingridge NMDA APV = AP5 (NMDA-R antagonist)

38. APV blocks LTP induction APV Time (min) fEPSP slope (% of baseline)

39. EPSP’s Synaptic Activity NE, Ach, S receptors Change in Local excitability 1 2 Synapse LTP? A B The Dendritic Tree and Regulation of Action Potential Propagation

40. NMDAR Independent LTP 200 Hz Mossy Fiber Tetra-ethyl ammonium (K+ channel blocker) induced LTP

43. PTP PPF Other forms of synaptic plasticity: pre-pulse facilitation and post-tetanic potentiation

44. Synaptic strengthening: changes that may underlie LTP