Long-term potentiation

The long-term potentiation (narrow: long - term potentiation, LTP) is an observed phenomenon of nerve cells at synapses. It represents a form of synaptic plasticity dar. Under LTP is defined as a long-term (long -term) gain ( potentiation ) of synaptic transmission.

LTP and learning

Viewed from the perspective of our brain consists of learned skills, a morphological correlate in the form of a network of synaptic connections. Arises, for example, in the association cortex, the idea to pronounce a word, this particular network is activated and sends a characteristic pattern of action potentials. About more interconnections, this results in a highly differentiated, controlled in time and force contraction of different muscle groups - the utterance of the word. To learn new words or skills or improve constantly new interconnections are created and removed old, no longer used by interconnections activation and training. These remodeling processes are referred to as synaptic plasticity. On the neurons level learning is nothing else than the activity-dependent change of Verschaltungsmustern and functional processes. In order to realize these activity-dependent changes ( learning), neurons have different mechanisms, which may be more or less strongly developed in different neurons of each cerebral cortex areas. These include, for example, the

• Presynaptic gain ( presynaptic facilitation enhancement = )
• Posttetanische potentiation,
• Synaptic depression
• And the long-term potentiation (LTP).

Under LTP is defined as a long-lasting enhancement of synaptic transmission. The best-studied form of LTP occurs in the CA1 region of the hippocampus with the Schaffer collaterals at the synapses of the pyramidal cells. The hippocampus is necessary for human beings for the creation of episodic memory contents. Of mice and rats, it is known that the hippocampus is essential for spatial learning.

Until recently was the direct link between LTP at the CA1 synapses and learning even hypothetically, the Note has now been experimentally provided that, first, spatial learning in rats produced LTP ( Whitlock et al., Science 313.1093-1097 ), and secondly the elimination of maintenance of LTP has the deletion of previously created spatial memory contents result ( Pastalkova et al., Science 313, 1141-1144 ).

LTP in the development of the nervous system

During embryonic development significantly more neural interconnections are created, as will ultimately survive to adult humans. Approximately one third of all neurons during development is based. This redundancy is useful, as a kind of competition between neurons occurs, the survival of the neurons that make up calls to the right destinations in the brain.

For example, axons need to project from the primary motor cortex to motor neurons in the spinal cord.

Misguided neurons die off. This is done by missing, specific neurotrophins. Furthermore, survival of the properly conducted neurons only those who possess the most stable synaptic connections. Stable connections are strengthened while, this is done by LTP, while weak connections are decoupled, this is done by long-term depression (LTD )

• See also: synaptic plasticity

Cellular mechanism

In many areas of the brain, including the cerebral cortex, the amygdala, the cerebellum ( cerebellum) and glutamatergic synapses in the hippocampus occur that have some special characteristics. The most important feature is the presence of AMPA receptors ( subspecies of glutamate receptors ) and N-methyl -D-aspartate receptors ( NMDA receptor ). The latter stands out from the other ionotropic glutamate receptors thereby from that on the one hand he has a very large conductance calcium ions, is closed to the other at hyperpolarized membrane from the outside by a magnesium ion. In the LTP it comes to the following events at the synapse:

Others

In this way creates a self-reinforcing cycle ( feed-forward loop). Since this gain can last very long, they are called LTP. From learning theory perspective, the following points are of interest:

• NMDA receptors are receptors coincidence, that is, enhanced LTP occurs with synchronized firing of multiple neurons. For example, in sleep we observed a strong synchronization of neural populations. The Papez circuit is a chain of neurons that should be involved in the storage of information.
• NMDA neurons are modified by the ascending reticular activating system ( ARAS ). The transmitter noradrenaline ( from the locus coeruleus ), serotonin ( from the raphe nuclei ), acetylcholine (from the Ncl. Basalis of Meynert Theodor ) and dopamine ( from the substantia nigra) on the stimulation of their receptors mediate the closing of potassium channels and cause depolarization. Depolarized cells more sensitive to glutamate stimulation. Attention thus plays an important role in learning processes.
• A weak activation of NMDA synapses results in only a slight increase in the intracellular Ca concentration. This is exactly the opposite of LTP, namely the long-term depression (LTD ).

Hebbian learning rule and LTP

The Spaniard Santiago Ramon y Cajal postulated in 1894 that memory is formed by strengthening the link between existing neurons, resulting in the improvement of their transmission efficiency.

In 1900, it was believed that memory is not the product of the growth of new nerve cells and that the number of neurons does not increase significantly in the memory of an adult with the age.

Donald O. Hebb (1949 ) took up this idea, but went one step further: cells form new connections in order to improve the effectiveness of their transmission ( Hebb rule): When an axon of cell A, cell B and repeatedly energized and permanently contributes to the generation of action potentials in the cell B, as this results in or metabolic changes and metabolic changes in one or two cells, the effect that the efficiency of the cell A is greater with respect to the generation of action potentials in B in growth processes. ( Slang: What fires together, wires together. )

The theories mentioned could not be detected at this time, since the corresponding neurophysiological methods were only in the second half of the 20th century are available.

The LTP was discovered in 1966 by Terje Lomo and is still (eg, development of drugs that exploit the biological mechanisms of LTP to combat diseases such as Alzheimer's disease or Parkinson's disease ) is an important research topic.

Terje Lomo conducted a series of neurophysiological experiments on anesthetized rabbits to investigate the role of the hippocampus in relation to the STM. He notes that a single pulse of electrical stimulation of the tractus perforans an excitatory postsynaptic potential ( EPSP) evoked in the dentate gyrus. Lomo not expected that a brief high-frequency burst of stimulation will induce a long - lasting increase in the EPSPs. This was called then LTP. Together with his co-worker Timothy Bliss published Lomo 1973, the first properties of LTP in the hippocampus of rabbits.