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LTP. Overview. LTP as candidate mechanism for (Hebbian) learning in the brain at the level of neurons Hippocampus overview LTP, an introduction LTP mechanisms LTP studies (proof of LTP mechanisms). Learning.
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Overview • LTP as candidate mechanism for (Hebbian) learning in the brain at the level of neurons • Hippocampus overview • LTP, an introduction • LTP mechanisms • LTP studies (proof of LTP mechanisms)
Learning • Where does learning take place at the neuronal level? What do we mean when we say neurons are plastic? • Neurons are plastic at the synapses. • Change in synaptic connectivity might constitute the mechanism of learning
Hebbian Learning • "when an axon of cell A ... excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased" (Hebb, 1949) • Cells that fire together, wire together
Hebbian Learning, Continued A B C Pre-Synaptic Neuron Axon “Hebbian” learning Synaptic Cleft Dendrite Post-Synaptic Neuron
Mechanism for Hebbian Learning • LTP is a candidate mechanism for Hebbian learning (synaptic plasticity) • LTP is a persistent increase in synaptic strength (as measured by the amplitude of the EPSP) that can be rapidly induced by brief neural activity
Where does LTP occur • LTP has been found in mammalian neocortical regions, and in subcortical nuclei • LTP has also been found in the peripheral nervous system of mammals • LTP has mainly been studied in the hippocampus, a vital structure for memory
Histological Section of Hippocampus Legend EC = Entorhinal Cortex S = Subiculum DG = Dentate Gyrus CA3 = CA3 field CA1 = CA1 field (PrS = PreSubiculum) (PaS = ParaSubiculum)
Neurogenesis, An Aside • The dentate gyrus continuously creates new neurons! • New neurons necessary for learning across time delays (Shors et al, 2001) • New neurons necessary for generating random context which minimizes interference, creates distinct codes (Becker, 2005)
Original LTP Study • By Timothy Bliss and Terje Lomo (1973) • Done on an anaesthetized rabbit’s hippocampus • Brief, high-frequency stimulation of the perforant pathway input to the dentate gyrus produced a long lasting enhancement of the extracellular recorded field potential
General LTP Experimental Design Stimulation of a bundle of presynaptic axons Recording of monosynaptic EPSP
Typical Results Typical Results
LTP Recording Techniques • In Vivo – in live animals • In Vitro – slice preparations, taken out of animal and manipulated in lab • Extracellular recording – multiple neurons • Intracellular recording – single neuron
Properties of LTP • Rapid • Long Lasting effects • Specificity • Co-operative • Associative
How Does LTP Work? • LTP requires some sort of additive effect • High-frequency stimulation • Activation of synapses and depolarization of the postsynaptic neuron must occur at the same time • LTP additive effect takes place due to workings of glutamate receptors
Glutamate • Glutamate is an excitatory neurotransmitter in CA1 • There are two kinds of glutamate receptors: AMPA and NMDA • AMPA receptors are simple – the presence of glutamate opens channels for sodium (Na+) ions.
NMDA • Mg2+ blocks ion channel • When cell is depolarized, Mg2+ forced away • Ca2+, as well as Na+, can enter through ion channels