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Long-term Potentiation as a Physiological Phenomenon From Mechanisms of Memory by J. David Sweatt, Ph.D.

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Presentation on theme: "Long-term Potentiation as a Physiological Phenomenon From Mechanisms of Memory by J. David Sweatt, Ph.D."— Presentation transcript:

1 Long-term Potentiation as a Physiological Phenomenon From Mechanisms of Memory by J. David Sweatt, Ph.D.

2 The Cellular and Molecular Basis of Cognition

3 Memories are stored as alterations in the strength of synaptic connections between neurons in the CNS. “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.

4 From Sidney Harris

5 Memories are stored as alterations in the strength of synaptic connections between neurons in the CNS. “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.

6 TVP Bliss, FRS

7

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

9 Bliss and Lomo’s First Published LTP Experiment

10 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 The Entorhinal/Hippocampal System Stratum Lacunosom Molecular inputs Recurrent Connections SLM Inputs Dopamine,

11 The Dendritic Tree

12 The Dendritic Spine

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14 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 The Entorhinal/Hippocampal System Stratum Lacunosom Molecular inputs Recurrent Connections SLM Inputs Dopamine,

15 Stimulating Electrode Recording Electrode Electrodes in a Living Hippocampal Slice

16 Tissue Slice Chamber

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18 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

19 B A An Input/Output Curve and a Typical LTP Experiment

20 From Nicoll et al.

21 Malenka et al, Bear et al, Huganir et al.

22 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.

23 LTP Triggered by Theta Burst Stimulation

24 Voltage Clamp Cell Body

25 Pairing LTP

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27 ASSOCIATIVE LTP German Barrionuevo and Tom Brown

28 Back Propagating Action Potentials

29 Pairing LTP

30 NEURONAL INFORMATION PROCESSING

31 MOLECULAR MECHANISMS NMDA APV = AP5 Graham Collingridge

32 APV Time (min) fEPSP slope (% of baseline) APV Block of LTP

33 Gly Glu Synaptic Glutamate Alone Cytoplasm Synaptic Cleft Mg ++ Ca ++ Glu Ca Mg ++ Gly Glutamate plus Membrane Depolarization CytoplasmSynaptic Cleft Ca ++ Coincidence Detection by the NMDA Receptor

34 Back Propagating Action Potentials

35 Timing of Back-propagating Action Potentials with Synaptic Activity

36 EPSP’s Synaptic Activity NE Change in Local excitability 1 2 Synapse LTP? AB The Dendritic Tree and Regulation of Action Potential Propagation

37 NMDAR Independent LTP 200 Hz Mossy Fiber TEA LTP

38 PTPPPF

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