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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
• 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
Synaptic
Cleft
Dendrite
Post-Synaptic
Neuron
“Hebbian”
learning
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
Location of Hippocampus
Parasagital view of Brain Including
Hippocampus
Horizontal Slice
Histological Section of
Hippocampus
Legend
EC = Entorhinal Cortex
S = Subiculum
DG = Dentate Gyrus
CA3 = CA3 field
CA1 = CA1 field
(PrS = PreSubiculum)
(PaS = ParaSubiculum)
Hippocampal Connectivity
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
AMPA (Post-Synaptic)
NMDA
Long-Term Changes