LTP
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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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LTP

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Ltp

LTP


Overview

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

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

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

Hebbian Learning, Continued

A

B

C

Pre-Synaptic

Neuron

Axon

“Hebbian” learning

Synaptic

Cleft

Dendrite

Post-Synaptic

Neuron


Mechanism for 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

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

Location of Hippocampus


Parasagital view of brain including hippocampus

Parasagital view of Brain Including Hippocampus


Horizontal slice

Horizontal Slice


Histological section of hippocampus

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

Hippocampal Connectivity


Neurogenesis an aside

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

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

General LTP Experimental Design

Stimulation of a bundle of presynaptic axons

Recording of monosynaptic EPSP


Typical results

Typical Results

Typical Results


Ltp recording techniques

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

Properties of LTP

  • Rapid

  • Long Lasting effects

  • Specificity

  • Co-operative

  • Associative


How does ltp work

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

  • 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.


Ltp

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

AMPA (Post-Synaptic)


Ltp

NMDA


Long term changes

Long-Term Changes


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