MadSci Network: Neuroscience
Query:

Re: How does 'sensitization' of neurons work?

Date: Thu Aug 23 17:52:59 2001
Posted By: Lynn Nielsen-Bohlman, Faculty, Geriatric Psychiatry, Vanderbilt University Medical Center
Area of science: Neuroscience
ID: 989251847.Ns
Message:

Neural sensitization is the process by which the response of a neuron to a given stimulus is increased. This increase lasts a long time - weeks or months at least. A simple explanation of sensitization is available at the UTHSC web page of Dr. Cynthia Miller http://www.sahs .uth.tmc.edu/brainsurf/aplysia1.html. Here is an example in a sea slug called Aplysia (a more detailed discussion of the aplysia model of sensitization is available at http:// nba19.uth.tmc.edu/nrc/newsltr/winter95/nrcnews1.html):

A sensory neuron synapses on a motor neuron. The axon of the sensory neuron is very close to the dendrite of the motor neuron. The axon of the sensory neuron sends a chemical signal called a neurotransmitter to the dendrite of the motor neuron. (In Aplysia the primary neurotransmitter involved is serotonin.) These neurotransmitters are released from the axon of the sensory nerve because of changes in locations of charged calcium, magnesium, sodium, potassium and chloride molecules (called ions). The neurotransmitter interacts with the cell wall (or membrane) of the postsynaptic motor neuron to change the location of ions in the motor neuron, which causes an electrical change in the motor neuron called the post-synaptic potential or PSP. Sensitization usually results from the convergence of two or more inputs on a neuron which bears the appropriate type of receptor, called an NMDA receptor. Sensitization is a neuromodulatory process, in which serotonin commonly serves as the neuromodulator, and cAMP is the second messenger.

In an unsensitized animal, when we stimulate the sensory neuron with a single electric pulse, the response of the motor neuron is small. This is shown in the figure below:

In the unsensitized animal, the PSP is about 0.5 millivolts. The motor neuron PSP causes the animal to pull its mouth in (siphon withdrawal) for less than 50 seconds. If we stimulate the sensory neuron again, the motor neuron response is still small (the Pre and Post section of the figure). Now lets sensitize the sensory-motor synapse by rapidly stimulating the sensory neuron with a burst of electric pulses for a short period of time. When we then stimulate the sensory neuron with a single electrical pulse, the PSP in the motor neuron is much larger, and the siphon withdrawal lasts longer. This is because the strength of the signal elicited in the motor neuron by the sensory neuron is much greater. The synapse between the sensory neuron and the motor neuron has been strengthened.

In the short term, the opening and closing of ion channels in the sensory and motor neurons are altered to produce a greater motor neuron and behavioral response. Serotonin affects the synthesis of the second messenger cyclic AMP, which in turn activates a protein kinase that closes down a channel through the membrane used by potassium ions. That prolongs the next nerve impulse in the terminal, which allows more calcium to enter the terminal and release of more serotonin.

In the long term, the changes in the ion channel opening and closing leads to changes in the number of connections or synapses between the sensory neuron and the motor neuron. This physical change in neuronal connection underlies long-term sensitization. Postsynaptic cyclic AMP release initiates long-term change. The proteins activated (or phosphorylated) by cyclic AMP in the short term can be maintained in this state in the long term by manufacture of new proteins (protein synthesis). A second event which converts short term changes to long term synaptic changes is the release of molecules called retrograde messengers. These molecules are synthesized in the postsynaptic motor neuron as a result of presynaptic events. Retrograde messengers diffuse back into the presynaptic cell, where they stimulate neurotransmitter release. One retrograde messenger is arachadonic acid.

For more information, the following reference materials may be available to you:

Antonov I. Kandel ER. Hawkins RD. The contribution of facilitation of monosynaptic PSPs to dishabituation and sensitization of the Aplysia siphon withdrawal reflex. Journal of Neuroscience. 19(23):10438-50, 1999

Bailey CH. Chen M. Morphological basis of long-term habituation and sensitization in Aplysia. Science. 220(4592):91-3, 1983

Bailey CH. Giustetto M. Zhu H. Chen M. Kandel ER. A novel function for serotonin-mediated short-term facilitation in aplysia: conversion of a transient, cell-wide homosynaptic hebbian plasticity into a persistent, protein synthesis-independent synapse-specific enhancement. Proceedings of the National Academy of Sciences of the United States of America. 97(21):11581-6, 2000

Brunelli M. Castellucci V. Kandel ER. Synaptic facilitation and behavioral sensitization in Aplysia: possible role of serotonin and cyclic AMP. Science. 194(4270):1178-81, 1976

Frost WN. Clark GA. Kandel ER. Parallel processing of short-term memory for sensitization in Aplysia. Journal of Neurobiology. 19(4):297-334, 1988

Guillin O. Diaz J. Carroll P. Griffon N. Schwartz JC. Sokoloff P. BDNF controls dopamine D3 receptor expression and triggers behavioural sensitization. Nature. 411(6833):86-9, 2001

Harman V.S. Peeke, Lewis Petrinovich.(eds) Habituation, sensitization, and behavior, Behavioral biology series, Orlando: Academic Press, 1984.

Klein M. Kandel ER. Mechanism of calcium current modulation underlying presynaptic facilitation and behavioral sensitization in Aplysia. Proceedings of the National Academy of Sciences of the United States of America. 77(11):6912-6, 1980

Kupfermann I. Modulatory actions of neurotransmitters. Annual Review of Neuroscience. 2:447-65, 1979

Nolen TG. Carew TJ. The cellular analog of sensitization in Aplysia emerges at the same time in development as behavioral sensitization. Journal of Neuroscience. 8(1):212-22, 1988

Images in this response were obtained from http:// www.emory.edu/CHEMISTRY/justice/chem190j/plastici.htm


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