Synaptic plasticity
Encyclopedia
In neuroscience
, synaptic plasticity is the ability of the connection, or synapse
, between two neuron
s to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse. There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of neurotransmitter
s released into a synapse and changes in how effectively cells respond to those neurotransmitters. Synaptic plasticity in both excitatory and inhibitory synapses has been found to be dependent upon calcium
. Since memories
are postulated to be represented by vastly interconnected networks of synapses in the brain
, synaptic plasticity is one of the important neurochemical foundations of learning
and memory
(see Hebbian theory
).
(LTP) in a publication in the Journal of Physiology. The experiment described was conducted on the synapse between the perforant path and dentate gyrus in the hippocampi of anaethetised rabbits. They were able to show a burst of tetanic (100 Hz) stimulus on perforant path fibres led to a dramatic and long-lasting augmentation in the post-synaptic response of cells onto which these fibres synapse in the dendate gyrus. Soon following, in the same year, the pair published very similar data recorded from awake rabbits. This discovery was of particular interest due to the proposed role of the hippocampus in certain forms of memory.
and AMPA
glutamate receptors. Opening of NMDA channels (which relates to the level of cellular depolarization) leads to a rise in post-synaptic Ca2+ concentration and this has been linked to LTP (as well as to protein kinase activation); strong depolarization of the post-synaptic cell completely displaces the magnesium ions that block NMDA ion channels and allows calcium ions to enter a cell – probably causing long-term potentiation (LTP), while weaker depolarization only partially displaces the Mg2+ ions, resulting in less Ca2+ entering the post-synaptic neuron and lower intracellular Ca2+ concentrations (which activate protein phosphatases and induce long-term depression, LTD).
These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. AMPA receptor
s), improving cation conduction, and thereby potentiating the synapse. Also, this signals recruitment of additional receptors into the post-synaptic membrane, and stimulates the production of a modified receptor type, thereby facilitating an influx of calcium. This in turn increases post-synaptic excitation by a given pre-synaptic stimulus. This process can be reversed via the activity of protein phosphatases, which act to dephosphorylate these cation channels.
The second mechanism depends on a second messenger cascade regulating gene transcription
and changes in the levels of key proteins at synapses such as CaMKII and PKAII. Activation of the second messenger pathway leads to increased levels of CaMKII and PKAII within the dendritic spine. These protein kinases have been linked to growth in dendritic spine volume and LTP processes such as the addition of AMPA receptors to the plasma membrane and phosphorylation of ion channels for enhanced permeability. Localization or compartmentalization of activated proteins occurs in the presence of their given stimulus which creates local effects in the dendritic spine. Calcium influx from NMDA receptors is necessary for the activation of CaMKII. This activation is localized to spines with focal stimulation and is inactivated before spreading to adjacent spines or the shaft, indicating an important mechanism of LTP in that particular changes in protein activation can be localized or compartmentalized to enhance the responsivity of single dendritic spines. Individual dendritic spines are capable of forming unique responses to presynaptic cells. This second mechanism can be triggered by protein phosphorylation but takes longer and lasts longer, providing the mechanism for long-lasting memory storage. The duration of the LTP can be regulated by breakdown of these second messengers. Phosphodiesterase
, for example, is a protein phosphatase that breaks down the secondary messenger cAMP
, which has been implicated in increased AMPA receptor synthesis in the post-synaptic neuron.
Long-lasting changes in the efficacy of synaptic connections (long-term potentiation
, or LTP) between two neurons can involve the making and breaking of synaptic contacts. Genes such as activin ß-A, which encodes a subunit of activin A, are up-regulated during early stage LTP. The activin molecule modulates the actin dynamics in dentritic spines through the MAP kinase pathway. By changing the F-actin cytoskeletal structure of dendritic spines, spines are lengthened and the chance that they make synaptic contacts with the axonal terminals of the presynaptic cell is increased. The end result is long term maintenance of LTP.
The number of ion channels on the post-synaptic membrane affects the strength of the synapse. Research suggests that the density of receptors on post-synaptic membranes changes, affecting the neuron’s excitability in response to stimuli. In a dynamic process that is maintained in equilibrium, N-methyl D-aspartate receptor (NMDA receptor)
and AMPA receptors are added to the membrane by exocytosis
and removed by endocytosis
. These processes, and by extension the number of receptors on the membrane, can be altered by synaptic activity. Experiments have shown that AMPA receptors are delivered to the synapse through vesicular membrane fusion with the postsynaptic membrane via the protein kinase CaMKII, which is activated by the influx of calcium through NMDA receptors. CaMKII also improves AMPA ionic conductance through phosphorylation.
When there is high-frequency NMDA receptor activation, there is an increase in the expression of a protein PSD-95 that increases synaptic capacity for AMPA receptors. This is what leads to a long-term increase in AMPA receptors and thus synaptic strength and plasticity.
If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a positive feedback loop will develop, causing some cells never to fire and some to fire too much. But two regulatory forms of plasticity, called scaling and metaplasticity
, also exist to provide negative feedback. Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.
Synaptic scaling serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small excitatory postsynaptic potential
s in response to continual excitation and raising them after prolonged blockage or inhibition. This effect occurs gradually over hours or days, by changing the numbers of NMDA receptor
s at the synapse (Pérez-Otaño and Ehlers, 2005). Metaplasticity
varies the threshold level at which plasticity occurs, allowing integrated responses to synaptic activity spaced over time and preventing saturated states of LTP and LTD. Since LTP and LTD (long-term depression
) rely on the influx of Ca2+
through NMDA channels, metaplasticity may be due to changes in NMDA receptors, altered calcium buffering, altered states of kinases or phosphatases and a priming of protein synthesis machinery. Synaptic scaling is a primary mechanism by which a neuron to be selective to its varying inputs.
The neuronal circuitry affected by LTP/LTD and modified by scaling and metaplasticity leads to reverberatory neural circuit development and regulation in a Hebbian manner which is manifested as memory, whereas the changes in neural circuitry, which begin at the level of the synapse, are an integral part in the ability of an organism to learn.
There is also a specificity element of biochemical interactions to create synaptic plasticity, namely the importance of location. Processes occur at microdomains – such as exocytosis of AMPA receptors is spatially regulated by the t-SNARE Stx4.
Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium.
The spatial gradient of PKA between dendritic spines and shafts is also important for the strength and regulation of synaptic plasticity. It is important to remember that the biochemical mechanisms altering synaptic plasticity occur at the level of individual synapses of a neuron. Since the biochemical mechanisms are confined to these "microdomains," the resulting synaptic plasticity affects only the specific synapse at which it took place.
, neural networks
, and biophysics
. Three major hypotheses for the molecular nature of this plasticity have been well-studied, and none are required to be the exclusive mechanism:
Of these, the first two hypotheses have been recently mathematically examined to have identical calcium-dependent dynamics which provides strong theoretical evidence for a calcium-based model of plasticity, which in a linear model where the total number of receptors are conserved looks like
where
is the synaptic weight
of the
th input axon, 
is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on 
, the concentration of calcium. 
is also a function of the concentration of calcium that depends linearly on the number of receptors on the membrane of the neuron at some fixed point. Both 
and 
are found experimentally and agree on results from both hypotheses. The model makes important simplifications that make it unsuited for actual experimental predictions, but provides a significant basis for the hypothesis of a calcium-based synaptic plasticity dependence.
, and post-tetanic potentiation
.
or depression is usually attributed to the depletion of the readily releasable vesicles. Depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.
Heterosynaptic
depression is thought to be linked to the release of adenosine triphosphate
(ATP) from astrocyte
s.
and long-term potentiation
are two forms of long-term plasticity, lasting minutes or more, that occur at excitatory synapses. NMDA-dependent LTD and LTP have been extensively researched, and are found to require the binding of glutamate, and glycine
or D-serine for activation of NMDA receptors.
s has been found to lead to a significant reduction of LTD in the hippocampus.
A LTD was evidenced in 2011 for the electrical synapses (modification of Gap Junctions efficacy through their activity).J. S. Haas, B. Zavala, C. E. Landisman, Activity-dependent long-term depression of electrical synapses. Science 334, 389–393 (2011). [Abstract] [Full Text].
, and the chemokine
, s100B
by astrocyte
s.
LTP is also a model for studying the synaptic basis of Hebbian plasticity. Induction conditions resemble those described for the initiation of long-term depression (LTD), but a stronger depolarization and a greater increase of calcium are necessary to achieve LTP.
s, the most researched type being astrocyte
s.
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
, synaptic plasticity is the ability of the connection, or synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
, between two neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s to change in strength in response to either use or disuse of transmission over synaptic pathways. Plastic change also results from the alteration of the number of receptors located on a synapse. There are several underlying mechanisms that cooperate to achieve synaptic plasticity, including changes in the quantity of neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s released into a synapse and changes in how effectively cells respond to those neurotransmitters. Synaptic plasticity in both excitatory and inhibitory synapses has been found to be dependent upon calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
. Since memories
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
are postulated to be represented by vastly interconnected networks of synapses in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, synaptic plasticity is one of the important neurochemical foundations of learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...
and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
(see Hebbian theory
Hebbian theory
Hebbian theory describes a basic mechanism for synaptic plasticity wherein an increase in synaptic efficacy arises from the presynaptic cell's repeated and persistent stimulation of the postsynaptic cell...
).
Historical discoveries
In 1973, Terje Lømo and Tim Bliss first described the now widely studied phenomenon of long-term potentiationLong-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
(LTP) in a publication in the Journal of Physiology. The experiment described was conducted on the synapse between the perforant path and dentate gyrus in the hippocampi of anaethetised rabbits. They were able to show a burst of tetanic (100 Hz) stimulus on perforant path fibres led to a dramatic and long-lasting augmentation in the post-synaptic response of cells onto which these fibres synapse in the dendate gyrus. Soon following, in the same year, the pair published very similar data recorded from awake rabbits. This discovery was of particular interest due to the proposed role of the hippocampus in certain forms of memory.
Biochemical mechanisms
Two molecular mechanisms for synaptic plasticity (researched by the Eric Kandel laboratories) involve the NMDANMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...
and AMPA
AMPA
AMPA is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate....
glutamate receptors. Opening of NMDA channels (which relates to the level of cellular depolarization) leads to a rise in post-synaptic Ca2+ concentration and this has been linked to LTP (as well as to protein kinase activation); strong depolarization of the post-synaptic cell completely displaces the magnesium ions that block NMDA ion channels and allows calcium ions to enter a cell – probably causing long-term potentiation (LTP), while weaker depolarization only partially displaces the Mg2+ ions, resulting in less Ca2+ entering the post-synaptic neuron and lower intracellular Ca2+ concentrations (which activate protein phosphatases and induce long-term depression, LTD).
These activated protein kinases serve to phosphorylate post-synaptic excitatory receptors (e.g. AMPA receptor
AMPA receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fast synaptic transmission in the central nervous system . Its name is derived from its ability to be activated by the artificial glutamate analog AMPA...
s), improving cation conduction, and thereby potentiating the synapse. Also, this signals recruitment of additional receptors into the post-synaptic membrane, and stimulates the production of a modified receptor type, thereby facilitating an influx of calcium. This in turn increases post-synaptic excitation by a given pre-synaptic stimulus. This process can be reversed via the activity of protein phosphatases, which act to dephosphorylate these cation channels.
The second mechanism depends on a second messenger cascade regulating gene transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
and changes in the levels of key proteins at synapses such as CaMKII and PKAII. Activation of the second messenger pathway leads to increased levels of CaMKII and PKAII within the dendritic spine. These protein kinases have been linked to growth in dendritic spine volume and LTP processes such as the addition of AMPA receptors to the plasma membrane and phosphorylation of ion channels for enhanced permeability. Localization or compartmentalization of activated proteins occurs in the presence of their given stimulus which creates local effects in the dendritic spine. Calcium influx from NMDA receptors is necessary for the activation of CaMKII. This activation is localized to spines with focal stimulation and is inactivated before spreading to adjacent spines or the shaft, indicating an important mechanism of LTP in that particular changes in protein activation can be localized or compartmentalized to enhance the responsivity of single dendritic spines. Individual dendritic spines are capable of forming unique responses to presynaptic cells. This second mechanism can be triggered by protein phosphorylation but takes longer and lasts longer, providing the mechanism for long-lasting memory storage. The duration of the LTP can be regulated by breakdown of these second messengers. Phosphodiesterase
Phosphodiesterase
A phosphodiesterase is any enzyme that breaks a phosphodiester bond. Usually, people speaking of phosphodiesterase are referring to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below...
, for example, is a protein phosphatase that breaks down the secondary messenger cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
, which has been implicated in increased AMPA receptor synthesis in the post-synaptic neuron.
Long-lasting changes in the efficacy of synaptic connections (long-term potentiation
Long-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
, or LTP) between two neurons can involve the making and breaking of synaptic contacts. Genes such as activin ß-A, which encodes a subunit of activin A, are up-regulated during early stage LTP. The activin molecule modulates the actin dynamics in dentritic spines through the MAP kinase pathway. By changing the F-actin cytoskeletal structure of dendritic spines, spines are lengthened and the chance that they make synaptic contacts with the axonal terminals of the presynaptic cell is increased. The end result is long term maintenance of LTP.
The number of ion channels on the post-synaptic membrane affects the strength of the synapse. Research suggests that the density of receptors on post-synaptic membranes changes, affecting the neuron’s excitability in response to stimuli. In a dynamic process that is maintained in equilibrium, N-methyl D-aspartate receptor (NMDA receptor)
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
and AMPA receptors are added to the membrane by exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
and removed by endocytosis
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...
. These processes, and by extension the number of receptors on the membrane, can be altered by synaptic activity. Experiments have shown that AMPA receptors are delivered to the synapse through vesicular membrane fusion with the postsynaptic membrane via the protein kinase CaMKII, which is activated by the influx of calcium through NMDA receptors. CaMKII also improves AMPA ionic conductance through phosphorylation.
When there is high-frequency NMDA receptor activation, there is an increase in the expression of a protein PSD-95 that increases synaptic capacity for AMPA receptors. This is what leads to a long-term increase in AMPA receptors and thus synaptic strength and plasticity.
If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a positive feedback loop will develop, causing some cells never to fire and some to fire too much. But two regulatory forms of plasticity, called scaling and metaplasticity
Metaplasticity
Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of individual synapses. However this new form referred to the plasticity of the plasticity itself, thus...
, also exist to provide negative feedback. Synaptic scaling is a primary mechanism by which a neuron is able to stabilize firing rates up or down.
Synaptic scaling serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small excitatory postsynaptic potential
Postsynaptic potential
Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials...
s in response to continual excitation and raising them after prolonged blockage or inhibition. This effect occurs gradually over hours or days, by changing the numbers of NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s at the synapse (Pérez-Otaño and Ehlers, 2005). Metaplasticity
Metaplasticity
Metaplasticity is a term originally coined by W.C. Abraham and M.F. Bear to refer to the plasticity of synaptic plasticity. Until that time synaptic plasticity had referred to the plastic nature of individual synapses. However this new form referred to the plasticity of the plasticity itself, thus...
varies the threshold level at which plasticity occurs, allowing integrated responses to synaptic activity spaced over time and preventing saturated states of LTP and LTD. Since LTP and LTD (long-term depression
Long-term depression
Long-term depression , in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress...
) rely on the influx of Ca2+
Calcium in biology
Calcium plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization...
through NMDA channels, metaplasticity may be due to changes in NMDA receptors, altered calcium buffering, altered states of kinases or phosphatases and a priming of protein synthesis machinery. Synaptic scaling is a primary mechanism by which a neuron to be selective to its varying inputs.
The neuronal circuitry affected by LTP/LTD and modified by scaling and metaplasticity leads to reverberatory neural circuit development and regulation in a Hebbian manner which is manifested as memory, whereas the changes in neural circuitry, which begin at the level of the synapse, are an integral part in the ability of an organism to learn.
There is also a specificity element of biochemical interactions to create synaptic plasticity, namely the importance of location. Processes occur at microdomains – such as exocytosis of AMPA receptors is spatially regulated by the t-SNARE Stx4.
Specificity is also an important aspect of CAMKII signaling involving nanodomain calcium.
The spatial gradient of PKA between dendritic spines and shafts is also important for the strength and regulation of synaptic plasticity. It is important to remember that the biochemical mechanisms altering synaptic plasticity occur at the level of individual synapses of a neuron. Since the biochemical mechanisms are confined to these "microdomains," the resulting synaptic plasticity affects only the specific synapse at which it took place.
Theoretical mechanisms
A bidirectional model, describing both LTP and LTD, of synaptic plasticity has proved necessary for a number of different learning mechanisms in computational neuroscienceComputational neuroscience
Computational neuroscience is the study of brain function in terms of the information processing properties of the structures that make up the nervous system...
, neural networks
Neural Networks
Neural Networks is the official journal of the three oldest societies dedicated to research in neural networks: International Neural Network Society, European Neural Network Society and Japanese Neural Network Society, published by Elsevier...
, and biophysics
Biophysics
Biophysics is an interdisciplinary science that uses the methods of physical science to study biological systems. Studies included under the branches of biophysics span all levels of biological organization, from the molecular scale to whole organisms and ecosystems...
. Three major hypotheses for the molecular nature of this plasticity have been well-studied, and none are required to be the exclusive mechanism:
- Change in the probability of glutamate release.
- Insertion or removal of post-synaptic AMPA receptors.
- PhosphorylationPhosphorylationPhosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
and de-phosphorylation inducing a change in AMPA receptor conductance.
Of these, the first two hypotheses have been recently mathematically examined to have identical calcium-dependent dynamics which provides strong theoretical evidence for a calcium-based model of plasticity, which in a linear model where the total number of receptors are conserved looks like
where
is the synaptic weightSynaptic weight
In neuroscience and computer science, synaptic weight refers to the strength or amplitude of a connection between two nodes, corresponding in biology to the amount of influence the firing of one neuron has on another...
of the
th input axon, is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on , the concentration of calcium. is also a function of the concentration of calcium that depends linearly on the number of receptors on the membrane of the neuron at some fixed point. Both and are found experimentally and agree on results from both hypotheses. The model makes important simplifications that make it unsuited for actual experimental predictions, but provides a significant basis for the hypothesis of a calcium-based synaptic plasticity dependence.Short-term plasticity
Plasticity can be categorized as short-term, lasting a few seconds or less, or long-term, which lasts from minutes to hours. Short-term synaptic enhancement results from an increase in the probability that synaptic terminals will release transmitters in response to pre-synaptic action potentials. Synapses will strengthen for a short time because of either an increase in size of the readily releasable pool of packaged transmitter or an increase in the amount of packaged transmitter released in response to each action potential. Types of short term plasticity include synaptic augmentation, depression, facilitation, or neural facilitationNeural facilitation
Neural facilitation, also known as paired pulse facilitation, is a concept in neuroscience where an increase in the postsynaptic potential is evoked by a second impulse....
, and post-tetanic potentiation
Post-Tetanic Potentiation
Post-Tetanic Potentiation is a form of synaptic plasticity which is short-lived and results in increased frequency with no effect on amplitude in the spontaneous postsynaptic potential. It usually lasts in the range of several minutes...
.
Synaptic augmentation
Synaptic augmentation is the increased efficacy of synapse lasting in the order of seconds (7 s often quoted). It has been found to be associated with increased efficiency with which action potentials cause release of vesicles containing transmitters.Synaptic depression
Synaptic fatigueSynaptic fatigue
Synaptic fatigue, or short-term synaptic depression, is an activity-dependent form of short-term plasticity that affects neuronal efficacy and results in the temporary inability to fire and therefore transmit an input signal. It is thought to be a form of negative feedback in order to...
or depression is usually attributed to the depletion of the readily releasable vesicles. Depression can also arise from post-synaptic processes and from feedback activation of presynaptic receptors.
Heterosynaptic
Heterosynaptic
Heterosynaptic phenomena are events that occur at the junctions that form connections between neurons. A heterosynaptic phenomenon is one that involves interactions between separate synapses or groups of synapses. This term is often used in relation to long-term depression and long-term...
depression is thought to be linked to the release of adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
(ATP) from astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s.
Long-term plasticity
Long-term depressionLong-term depression
Long-term depression , in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress...
and long-term potentiation
Long-term potentiation
In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
are two forms of long-term plasticity, lasting minutes or more, that occur at excitatory synapses. NMDA-dependent LTD and LTP have been extensively researched, and are found to require the binding of glutamate, and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
or D-serine for activation of NMDA receptors.
Long-term depression
Brief activation of an excitatory pathway can produce what is known as long-term depression (LTD) of synaptic transmission in many areas of the brain. LTD is induced by a minimum level of postsynaptic depolarization and simultaneous increase in the intracellular calcium concentration at the postsynaptic neuron. LTD can be initiated at inactive synapses if the calcium concentration is raised to the minimum required level by heterosynaptic activation, or if the extracellular concentration is raised. These alternative conditions capable of causing LTD differ from the Hebb rule, and instead depend on synaptic activity modifications. D-serine release by astrocyteAstrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s has been found to lead to a significant reduction of LTD in the hippocampus.
A LTD was evidenced in 2011 for the electrical synapses (modification of Gap Junctions efficacy through their activity).J. S. Haas, B. Zavala, C. E. Landisman, Activity-dependent long-term depression of electrical synapses. Science 334, 389–393 (2011). [Abstract] [Full Text].
Long-term potentiation
Long-term potentiation, commonly referred to as LTP, is an increase in synaptic response following potentiating pulses of electrical stimuli that sustains at a level above the baseline response for hours or longer. LTP involves interactions between postsynaptic neurons and the specific presynaptic inputs that form a synaptic association, and is specific to the stimulated pathway of synaptic transmission. Modification of astrocyte coverage at the synapses in the hippocampus has been found to result from the induction of LTP, which has been found to be linked to the release of D-serine, nitric oxideNitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
, and the chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
, s100B
S100B
S100 calcium binding protein B or S100B is a protein of the S-100 protein family.S100 proteins are localized in the cytoplasm and nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation...
by astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s.
LTP is also a model for studying the synaptic basis of Hebbian plasticity. Induction conditions resemble those described for the initiation of long-term depression (LTD), but a stronger depolarization and a greater increase of calcium are necessary to achieve LTP.
Synaptic strength
The modification of synaptic strength is referred to as functional plasticity. Changes in synaptic strength involve distinct mechanisms of particular types of glial cellGlial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s, the most researched type being astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...
s.
See also
- BCM theoryBCM theoryBCM theory, BCM synaptic modification, or the BCM rule, named for Elie Bienenstock, Leon Cooper, and Paul Munro, is a physical theory of learning in the visual cortex developed in 1981...
- Excitatory postsynaptic potentialExcitatory postsynaptic potentialIn neuroscience, an excitatory postsynaptic potential is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels...
- Homeostatic plasticityHomeostatic plasticityIn Neuroscience, homeostatic plasticity refers to the capacity of neurons to regulate their own excitability relative to network activity, a compensatory adjustment that occurs over the timescale of days....
- Inhibitory postsynaptic potentialInhibitory postsynaptic potentialAn inhibitory postsynaptic potential is a synaptic potential that decreases the chance that a future action potential will occur in a postsynaptic neuron or α-motoneuron...
- Long-term potentiationLong-term potentiationIn neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...
(LTP) - Long-term depressionLong-term depressionLong-term depression , in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress...
(LTD) - Activity-dependent plasticityActivity-dependent plasticityA defining feature of the brain is its capacity to undergo changes based on activity-dependent functions, also called activity-dependent plasticity. Its ability to remodel itself forms the basis of the brain’s capacity to retain memories, improve motor function, and enhance comprehension and...
- Spike-timing-dependent plasticity (STDP)
- Synaptic augmentation (Short-term plasticity)
- Neural facilitationNeural facilitationNeural facilitation, also known as paired pulse facilitation, is a concept in neuroscience where an increase in the postsynaptic potential is evoked by a second impulse....
(Short-term plasticity) - NeuroplasticityNeuroplasticityNeuroplasticity is a non-specific neuroscience term referring to the ability of the brain and nervous system in all species to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in...
- Postsynaptic potentialPostsynaptic potentialPostsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to initiate or inhibit action potentials...
- Non-synaptic plasticityNon-synaptic plasticityNonsynaptic plasticity is a form of neuroplasticity that involves modification of ion channel function in the axon, dendrites, and cell body that results in specific changes in the integration of Excitatory postsynaptic potentials and Inhibitory postsynaptic potentials. Nonsynaptic plasticity is a...
External links
- Overview
- Finnerty lab, MRC Centre for Neurodegeneration Research, London
- Brain Basics Synaptic Plasticity Synaptic transmission is plastic
- Synaptic Plasticity, Neuroscience Online (electronic neuroscience textbook by UT Houston Medical School)
Videos, podcasts
- Synaptic plasticity: Multiple mechanisms and functions - a lecture by Robert Malenka, M.D., Ph.D., Stanford UniversityStanford UniversityThe Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
. Video podcast, runtime: 01:05:17.