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This comprehensive overview delves into long-term potentiation (LTP) as a key physiological phenomenon underlying memory formation. It examines the intricate workings of the entorhinal-hippocampal system, detailing pathways such as the perforant pathway, dentate gyrus, and CA1 region. The study highlights significant experiments, including Bliss and Lomo’s pioneering work on LTP, and discusses molecular inputs from neurotransmitters like norepinephrine, acetylcholine, and dopamine. The role of synaptic activity, NMDA receptors, and the effects of burst stimulation on LTP are thoroughly analyzed.
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Long-term Potentiation as a Physiological Phenomenon From Mechanisms of Memory by J. David Sweatt, Ph.D.
The Entorhinal/Hippocampal System Entorhinal Cortex Perforant Pathway Dentate Gyrus Stratum Lacunosom Molecular inputs Mossy Fiber Lateral Septum, Contralateral CA1 CA1 Axon CA3 Schaffer Collaterals Recurrent Connections GABAergic Interneuron Ipsilateral CA1 Norepinephrine, Acetylcholine, Entorhinal Cortex Dopamine, Amygdala, Cortex Serotonin SLM Inputs Schaffer Collaterals Lateral Septum Subiculum
Electrodes in a Living Hippocampal Slice Stimulating Electrode Recording Electrode
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
APV fEPSP slope (% of baseline) Time (min) APV Block of LTP Figure 6: APV Block of LTP
A 100-Hz 100-Hz 100-Hz 100-Hz 200 msec … 200 msec 200 msec 10 msec between pulses • 5-Hz burst frequency • 10 bursts per train • 3 trains, 20-sec intertrain interval B 200 175 150 fEPSP slope (% of baseline) 125 100 75 -20 0 20 40 60 Time (min) LTP Triggered by Theta Burst Stimulation
Coincidence Detection by the NMDA Receptor Cytoplasm Synaptic Cleft Synaptic Cleft Cytoplasm - - - - - - + + + + + + Ca++ Gly Gly Ca++ Mg++ Ca++ Mg++ Glu + + + + - - - - + + + + - - - - Glu Glutamate plus Membrane Depolarization Synaptic Glutamate Alone
Timing of Back-propagating Action Potentials with Synaptic Activity
The Dendritic Tree and Regulation of Action Potential Propagation A B NE Change in Local excitability 1 Synaptic Activity 2 EPSP’s LTP? Synapse
NMDAR independent LTP A C B
PPF PTP