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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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The Cellular and Molecular
Basis of Cognition
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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.
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From Sidney Harris
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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.
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TVP Bliss, FRS
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The Entorhinal/Hippocampal System
Cortex Perforant Pathway Dentate Gyrus Stratum Lacunosom Molecular inputs Mossy Fiber CA3 Schaffer Collaterals Recurrent Connections Ipsilateral CA1
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Bliss and Lomo’s First Published LTP Experiment
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The Entorhinal/Hippocampal System
Cortex Perforant Pathway Dentate Gyrus Stratum Lacunosom Molecular inputs Mossy Fiber Lateral Septum, Contralateral CA1 CA3 CA1 Axon Schaffer Collaterals Recurrent Connections GABAergic Interneuron Ipsilateral CA1 Norepinephrine, Acetylcholine, Entorhinal Cortex Amygdala, Cortex Dopamine, Serotonin SLM Inputs Lateral Septum Schaffer Collaterals Subiculum
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The Dendritic Tree
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The Dendritic Spine
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The Entorhinal/Hippocampal System
Cortex Perforant Pathway Dentate Gyrus Stratum Lacunosom Molecular inputs Mossy Fiber Lateral Septum, Contralateral CA1 CA3 CA1 Axon Schaffer Collaterals Recurrent Connections GABAergic Interneuron Ipsilateral CA1 Norepinephrine, Acetylcholine, Entorhinal Cortex Amygdala, Cortex Dopamine, Serotonin SLM Inputs Lateral Septum Schaffer Collaterals Subiculum
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Electrodes in a Living Hippocampal Slice
Stimulating Electrode Recording Electrode
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Tissue Slice Chamber
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Recording Configuration and Typical Responses in a Hippocampal Slice Recording Experiment
Recording in Stratum Pyramidale in Area CA1 Stimulating Schaffer Collaterals in Area CA3 Recording in Stratum Radiatum in Area CA1 Stimulus Artifact Fiber Volley EPSP
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An Input/Output Curve and a Typical LTP Experiment
B
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From Nicoll et al.
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Malenka et al, Bear et al, Huganir et al.
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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.
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LTP Triggered by Theta Burst Stimulation
… 100-Hz 200 msec 10 msec between pulses 5-Hz burst frequency 10 bursts per train 3 trains, 20-sec intertrain interval A B Time (min) fEPSP slope (% of baseline) -20 20 40 60 75 100 125 150 175
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Voltage Clamp Cell Body
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Pairing LTP
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ASSOCIATIVE LTP German Barrionuevo and Tom Brown
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Back Propagating Action Potentials
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Pairing LTP
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NEURONAL INFORMATION PROCESSING
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MOLECULAR MECHANISMS NMDA Graham Collingridge APV = AP5
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APV Block of LTP APV Time (min) (% of baseline) fEPSP slope
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Coincidence Detection by the NMDA Receptor
Synaptic Cleft Cytoplasm Synaptic Cleft Cytoplasm + - - + Ca++ Gly Gly Ca++ Mg++ Ca++ Mg++ Glu + - + Glu - Glutamate plus Membrane Depolarization Synaptic Glutamate Alone
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Back Propagating Action Potentials
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Timing of Back-propagating Action Potentials with Synaptic Activity
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The Dendritic Tree and Regulation of Action Potential Propagation
B NE Change in Local excitability 1 Synaptic Activity 2 EPSP’s LTP? Synapse
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200 Hz Mossy Fiber TEA LTP NMDAR Independent LTP
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PPF PTP
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