Dendritic spine
Encyclopedia
A dendritic spine is a small membranous protrusion from a neuron's dendrite
that typically receives input from a single synapse
of an axon
. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have a bulbous head (the spine head), and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons.
Spines are found on the dendrite
s of most principal neuron
s in the brain, including the pyramidal neurons
of the neocortex
, the medium spiny neurons of the striatum
, and the Purkinje cell
s of the cerebellum
.
Dendritic spines occur at a density of up to 50 spines/10 µm stretch of dendrite. Hippocampal
and cortical pyramidal neurons
may receive tens of thousands of mostly excitatory inputs from other neurons onto their equally numerous spines, whereas the number of spines on Purkinje neuron dendrites is an order of magnitude larger.
and NMDA receptor
) on their surface. The TrkB
receptor for BDNF is also expressed on the spine surface, and is believed to play a role in spine survival. The tip of the spine contains an electrondense region referred to as the "postsynaptic density
" (PSD). The PSD directly apposes the active zone
of its synapsing axon and comprises ~10% of the spine's membrane surface area; neurotransmitters released from the active zone bind receptors in the postsynaptic density of the spine. One-half of the synapsing axons and dendritic spines are physically tethered by calcium
-dependent cadherin
, which forms cell-to-cell adherent junctions between two neurons.
Glutamate receptors (GluRs) are localized to the postsynaptic density, and are anchored by cytoskeletal elements to the membrane. They are positioned directly above their signaling machinery, which is typically tethered to the underside of the plasma membrane, allowing signals transmitted by the GluRs into the cytosol
to be further propagated by their nearby signaling elements to activate signal transduction cascades. The localization of signaling elements to their GluRs is particularly important in ensuring signal cascade activation, as GluRs would be unable to affect particular downstream effects without nearby signalers.
Signaling from GluRs is mediated by the presence of an abundance of proteins, especially kinases, that are localized to the postsynaptic density. These include calcium
-dependent calmodulin
, CaMKII (calmodulin-dependent protein kinase II), PKC
(Protein Kinase C), PKA (Protein Kinase A), Protein Phosphatase-1 (PP-1), and Fyn tyrosine kinase. Certain signalers, such as CaMKII, are upregulated in response to activity.
Spines are particularly advantageous to neurons by compartmentalizing biochemical signals. This can help to encode changes in the state of an individual synapse without necessarily affecting the state of other synapses of the same neuron. The length and width of the spine neck has a large effect on the degree of compartmentalization, with thin spines being the most biochemically isolated spines.
monomers and microtubule-associated protein
s (MAPs) are present, organized microtubule
s are not present. Because spines have a cytoskeleton of primarily actin, this allows them to be highly dynamic in shape and size. The actin cytoskeleton directly determines the morphology of the spine, and actin regulators, small GTPase
s such as Rac
, RhoA
, and CDC42
, rapidly modify this cytoskeleton. Overactive Rac1
results in consistently smaller dendritic spines.
In addition to their electrophysiological activity and their receptor-mediated activity, spines appear to be vesicularly active and may even translate protein
s. Stacked discs of the smooth endoplasmic reticulum (SERs) have been identified in dendritic spines. Formation of this "spine apparatus
" depends on the protein synaptopodin and is believed to play an important role in calcium handling. "Smooth" vesicle
s have also been identified in spines, supporting the vesicular activity in dendritic spines. The presence of polyribosomes in spines also suggests protein translational activity in the spine itself, not just in the dendrite.
cytoskeleton
, they are dynamic, and the majority of spines change their shape within seconds to minutes because of the dynamicity of actin remodeling
. Furthermore, spine number is very variable and spines come and go; in a matter of hours, 10-20% of spines can spontaneously appear or disappear on the pyramidal cells of the cerebral cortex, although the larger "mushroom"-shaped spines are the most stable.
Spine maintenance and plasticity is activity-dependent and activity-independent. BDNF partially determines spine levels, and low levels of AMPA receptor
activity is necessary to maintain spine survival, and synaptic activity involving NMDA receptor
s encourages spine growth. Furthermore, two-photon laser scanning microscopy
and confocal microscopy have shown that spine volume changes depending on the types of stimuli that are presented to a synapse.
, learning
, and memory
. In particular, long-term memory
is mediated in part by the growth of new dendritic spines (or the enlargement of pre-existing spines) to reinforce a particular neural pathway. Because dendritic spines are plastic structures whose lifespan is influenced by input activity, spine dynamics may play an important role in the maintenance of memory over a lifetime.
Age-dependent changes in the rate of spine turnover suggest that spine stability impacts developmental learning. In youth, dendritic spine turnover is relatively high and produces a net loss of spines, with the rate of the elimination of spines surpassing the rate of the formation of spines. This high rate of spine turnover may characterize critical periods of development and reflect learning capacity in adolescence—different cortical areas exhibit differing levels of synaptic turnover during development, possibly reflecting varying critical periods for specific brain regions. In adulthood, however, most spines remain persistent, and the half-life of spines increases. This stabilization occurs due to a developmentally regulated slow-down of spine elimination, a process which may underlie the stabilization of memories in maturity..
Experience-induced changes in dendritic spine stability also point to spine turnover as a mechanism involved in the maintenance of long-term memories, though it is unclear how sensory experience affects neural circuitry. Two general models might describe the impact of experience on structural plasticity. On the one hand, experience and activity may drive the discrete formation of relevant synaptic connections that store meaningful information in order to allow for learning. On the other hand, synaptic connections may be formed in excess, and experience and activity may lead to the pruning of extraneous synaptic connections.
In lab animals of all ages, environmental enrichment has been related to dendritic branching, spine density, and overall number of synapses. In addition, skill training has been shown to lead to the formation and stabilization of new spines while destabilizing old spines, suggesting that the learning of a new skill involves a rewiring process of neural circuits. Since the extent of spine remodeling correlates with success of learning, this suggests a crucial role of synaptic structural plasticity in memory formation. In addition, changes in spine stability and strengthening occur rapidly and have been observed within hours after training.
Conversely, while enrichment and training are related to increases in spine formation and stability, long-term sensory deprivation
leads to a decrease in the rate of spine elimination and therefore impacts long-term neural circuitry. Upon restoring sensory experience after deprivation in adolescence, spine elimination is accelerated, suggesting that experience plays an important role in the net loss of spines during development. In addition, other sensory deprivation paradigms—such as whisker trimming—have been shown to increase the stability of new spines.
Research in neurological diseases and injuries shed further light on the nature and importance of spine turnover. After stroke
, a marked increase in structural plasticity occurs near the trauma site, and a five- to eightfold increase from control rates in spine turnover has been observed. Dendrites disintegrate and reassemble rapidly during ischemia
—as with stroke, survivors showed an increase in dendritic spine turnover. While a net loss of spines is observed in Alzheimer's disease
and cases of mental retardation
, cocaine and amphetamine use have been linked to increases in dendritic branching and spine density in the prefrontal cortex
and the nucleus accumbens
. Because significant changes in spine density occur in various brain diseases, this suggests a balanced state of spine dynamics in normal circumstances, which may be susceptible to disequilibrium under varying pathological conditions.
There is also some evidence for loss of dendritic spines as a consequence of aging. One study using mice has noted a correlation between age-related reductions in spine densities in the hippocampus that and age-dependent declines in hippocampal learning and memory.
refers to the passive conduction of current. Dendritic spines have a number of specific electrotonic properties. A dendritic spine has high input resistance
, the resistance increases with smallness of headsize and narrowness of stemsize. The capacitance
of the membrane
s of spines is relatively small with the result that synaptic potentials can be relatively fast. The capacitance of the whole dendrite however becomes higher as the number of spines increases. Because there is an impedance mismatch
between the dendritic spine and the dendrite, it is necessary with active signal boosting. The impedance mismatch also causes the spine to follow the potential of the parent dendrite.
Cable theory
provides the theoretical framework behind the most "simple" method for modelling the flow of electrical currents along passive neural fibres. Each spine can be treated as two compartments, one representing the neck, the other representing the spine head. The compartment representing the spine head alone should carry the active properties.
s, which have a high permeability for calcium, only conduct ions if the membrane potential is suffiently depolarized. The amount of calcium entering a spine during synaptic activity therefore depends on the depolarization of the spine head. Evidence from calcium imaging experiments (two-photon microscopy) and from compartmental modelling indicates that spines with high resistance necks experience larger calcium transients during synaptic activity.
. During synaptogenesis
, dendrites rapidly sprout and retract filopodia, small membrane organelle-lacking membranous protrusions. During the first week of birth, the brain is predominated by filopodia, which eventually develop synapses. However, after this first week, filopodia are replaced by spiny dendrites but also small, stubby spines that protrude from spiny dendrites. In the development of certain filopodia into spines, filopodia recruit presynaptic contact to the dendrite, which encourages the production of spines to handle specialized postsynaptic contact with the presynaptic protrusions.
Spines, however, require maturation after formation. Immature spines have impaired signaling capabilities, and typically lack "heads" (or have very small heads), only necks, while matured spines maintain both heads and necks.
, mental retardation
, and fragile X syndrome
, may be resultant from abnormalities in dendritic spines, especially the number of spines and their maturity. The ratio of matured to immature spines is important in their signaling, as immature spines have impaired synaptic signaling. Fragile X syndrome is characterized by an overabundance of immature spines that have multiple filopodia in cortical dendrites.
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
that typically receives input from a single 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...
of an axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
. Dendritic spines serve as a storage site for synaptic strength and help transmit electrical signals to the neuron's cell body. Most spines have a bulbous head (the spine head), and a thin neck that connects the head of the spine to the shaft of the dendrite. The dendrites of a single neuron can contain hundreds to thousands of spines. In addition to spines providing an anatomical substrate for memory storage and synaptic transmission, they may also serve to increase the number of possible contacts between neurons.
Distribution
Dendritic spines usually receive excitatory input from axons although sometimes both inhibitory and excitatory connections are made onto the same spine head.Spines are found on the dendrite
Dendrite
Dendrites are the branched projections of a neuron that act to conduct the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project...
s of most principal 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 in the brain, including the pyramidal neurons
Pyramidal cell
Pyramidal neurons are a type of neuron found in areas of the brain including cerebral cortex, the hippocampus, and in the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons were first discovered and...
of the neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
, the medium spiny neurons of the striatum
Striatum
The striatum, also known as the neostriatum or striate nucleus, is a subcortical part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex...
, and the Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
s of the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
.
Dendritic spines occur at a density of up to 50 spines/10 µm stretch of dendrite. Hippocampal
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
and cortical pyramidal neurons
Pyramidal cell
Pyramidal neurons are a type of neuron found in areas of the brain including cerebral cortex, the hippocampus, and in the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cortex and the corticospinal tract. Pyramidal neurons were first discovered and...
may receive tens of thousands of mostly excitatory inputs from other neurons onto their equally numerous spines, whereas the number of spines on Purkinje neuron dendrites is an order of magnitude larger.
Morphology
Dendritic spines are small with spine head volumes ranging 0.01 µm3 to 0.8 µm3. Spines with strong synaptic contacts typically have a large spine head, which connect to the dendrite via a membranous neck. The most notable classes of spine shape are "thin", "stubby", "mushroom", and "branched". Electron microscopy studies have shown that there is a continuum of shapes between these categories. The variable spine shape and volume is thought to be correlated with the strength and maturity of each spine-synapse.Receptor activity
Dendritic spines express glutamate receptors (e.g. AMPA receptorAMPA 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...
and NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
) on their surface. The TrkB
TrkB
TrkB receptor also known as TrkB tyrosine kinase or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene.-Function:...
receptor for BDNF is also expressed on the spine surface, and is believed to play a role in spine survival. The tip of the spine contains an electrondense region referred to as the "postsynaptic density
Postsynaptic density
The postsynaptic density is a protein dense specialization attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron...
" (PSD). The PSD directly apposes the active zone
Active zone
The active zone is a term first used by Couteaux and Pecot-Dechavassinein in 1970 and is defined in the neuron as the site of neurotransmitter release. Neurons contain structures called synapses that allow for the communication from one neuron to another...
of its synapsing axon and comprises ~10% of the spine's membrane surface area; neurotransmitters released from the active zone bind receptors in the postsynaptic density of the spine. One-half of the synapsing axons and dendritic spines are physically tethered by 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...
-dependent cadherin
Cadherin
Cadherins are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that cells within tissues are bound together. They are dependent on calcium ions to function, hence their name.The cadherin superfamily includes cadherins, protocadherins, desmogleins, and...
, which forms cell-to-cell adherent junctions between two neurons.
Glutamate receptors (GluRs) are localized to the postsynaptic density, and are anchored by cytoskeletal elements to the membrane. They are positioned directly above their signaling machinery, which is typically tethered to the underside of the plasma membrane, allowing signals transmitted by the GluRs into the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
to be further propagated by their nearby signaling elements to activate signal transduction cascades. The localization of signaling elements to their GluRs is particularly important in ensuring signal cascade activation, as GluRs would be unable to affect particular downstream effects without nearby signalers.
Signaling from GluRs is mediated by the presence of an abundance of proteins, especially kinases, that are localized to the postsynaptic density. These include 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...
-dependent calmodulin
Calmodulin
Calmodulin is a calcium-binding protein expressed in all eukaryotic cells...
, CaMKII (calmodulin-dependent protein kinase II), PKC
Protein kinase C
Protein kinase C also known as PKC is a family of enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues on these proteins. PKC enzymes in turn are activated by signals such as increases in...
(Protein Kinase C), PKA (Protein Kinase A), Protein Phosphatase-1 (PP-1), and Fyn tyrosine kinase. Certain signalers, such as CaMKII, are upregulated in response to activity.
Spines are particularly advantageous to neurons by compartmentalizing biochemical signals. This can help to encode changes in the state of an individual synapse without necessarily affecting the state of other synapses of the same neuron. The length and width of the spine neck has a large effect on the degree of compartmentalization, with thin spines being the most biochemically isolated spines.
Cytoskeleton and Organelles
The cytoskeleton of dendritic spines is particularly important in their synaptic plasticity; without a dynamic cytoskeleton, spines would be unable to rapidly change their volumes or shapes in responses to stimuli. These changes in shape might affect the electrical properties of the spine. The cytoskeleton of dendritic spines is primarily made of filamentous actin (F-actin). While tubulinTubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
monomers and microtubule-associated protein
Microtubule-associated protein
In cell biology, microtubule-associated proteins are proteins that interact with the microtubules of the cellular cytoskeleton.-Function:...
s (MAPs) are present, organized microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
s are not present. Because spines have a cytoskeleton of primarily actin, this allows them to be highly dynamic in shape and size. The actin cytoskeleton directly determines the morphology of the spine, and actin regulators, small GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
s such as Rac
Rac (GTPase)
Rac is a subfamily of the Rho family of GTPases, small signaling G proteins .The subgroup include:*Rac1*Rac2*Rac3*RhoG...
, RhoA
RHOA
Ras homolog gene family, member A is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. In humans, it is encoded by the gene RHOA....
, and CDC42
CDC42
Cell division control protein 42 homolog also known as CDC42 is a protein involved in regulation of the cell cycle. In humans, CDC42 is encoded by the CDC42 gene.- Function :...
, rapidly modify this cytoskeleton. Overactive Rac1
RAC1
Ras-related C3 botulinum toxin substrate 1 also known as Rac1 is a protein that in humans is encoded by the RAC1 gene. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined.- Function :Rac1 is...
results in consistently smaller dendritic spines.
In addition to their electrophysiological activity and their receptor-mediated activity, spines appear to be vesicularly active and may even translate protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. Stacked discs of the smooth endoplasmic reticulum (SERs) have been identified in dendritic spines. Formation of this "spine apparatus
Spine apparatus
The spine apparatus is a specialized form of endoplasmic reticulum that is found in a subpopulation of dendritic spines in central neurons. It was discovered by E. G. Gray in 1959 when he applied electron microscopy to fixed cortical tissue. The SA consists of a series of stacked discs that are...
" depends on the protein synaptopodin and is believed to play an important role in calcium handling. "Smooth" vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s have also been identified in spines, supporting the vesicular activity in dendritic spines. The presence of polyribosomes in spines also suggests protein translational activity in the spine itself, not just in the dendrite.
Plasticity
As aforementioned, dendritic spines are very "plastic", that is, spines change significantly in shape, volume, and number in small time courses. Because spines have a primarily actinActin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
, they are dynamic, and the majority of spines change their shape within seconds to minutes because of the dynamicity of actin remodeling
Actin remodeling of neurons
Actin remodeling is a biochemical process in cells. In the actin remodeling of neurons, the protein actin is part of the process to change the shape and structure of dendritic spines. G-actin is the monomer form of actin, and is uniformly distributed throughout the axon and the dendrite...
. Furthermore, spine number is very variable and spines come and go; in a matter of hours, 10-20% of spines can spontaneously appear or disappear on the pyramidal cells of the cerebral cortex, although the larger "mushroom"-shaped spines are the most stable.
Spine maintenance and plasticity is activity-dependent and activity-independent. BDNF partially determines spine levels, and low levels of 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...
activity is necessary to maintain spine survival, and synaptic activity involving NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s encourages spine growth. Furthermore, two-photon laser scanning microscopy
Two-photon excitation microscopy
Two-photon excitation microscopy is a fluorescence imaging technique that allows imaging of living tissue up to a very high depth, that is up to about one millimeter. Being a special variant of the multiphoton fluorescence microscope, it uses red-shifted excitation light which can also excite...
and confocal microscopy have shown that spine volume changes depending on the types of stimuli that are presented to a synapse.
Evidence of Importance
Spine plasticity is implicated in motivationMotivation
Motivation is the driving force by which humans achieve their goals. Motivation is said to be intrinsic or extrinsic. The term is generally used for humans but it can also be used to describe the causes for animal behavior as well. This article refers to human motivation...
, 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....
. In particular, long-term memory
Long-term memory
Long-term memory is memory in which associations among items are stored, as part of the theory of a dual-store memory model. According to the theory, long term memory differs structurally and functionally from working memory or short-term memory, which ostensibly stores items for only around 20–30...
is mediated in part by the growth of new dendritic spines (or the enlargement of pre-existing spines) to reinforce a particular neural pathway. Because dendritic spines are plastic structures whose lifespan is influenced by input activity, spine dynamics may play an important role in the maintenance of memory over a lifetime.
Age-dependent changes in the rate of spine turnover suggest that spine stability impacts developmental learning. In youth, dendritic spine turnover is relatively high and produces a net loss of spines, with the rate of the elimination of spines surpassing the rate of the formation of spines. This high rate of spine turnover may characterize critical periods of development and reflect learning capacity in adolescence—different cortical areas exhibit differing levels of synaptic turnover during development, possibly reflecting varying critical periods for specific brain regions. In adulthood, however, most spines remain persistent, and the half-life of spines increases. This stabilization occurs due to a developmentally regulated slow-down of spine elimination, a process which may underlie the stabilization of memories in maturity..
Experience-induced changes in dendritic spine stability also point to spine turnover as a mechanism involved in the maintenance of long-term memories, though it is unclear how sensory experience affects neural circuitry. Two general models might describe the impact of experience on structural plasticity. On the one hand, experience and activity may drive the discrete formation of relevant synaptic connections that store meaningful information in order to allow for learning. On the other hand, synaptic connections may be formed in excess, and experience and activity may lead to the pruning of extraneous synaptic connections.
In lab animals of all ages, environmental enrichment has been related to dendritic branching, spine density, and overall number of synapses. In addition, skill training has been shown to lead to the formation and stabilization of new spines while destabilizing old spines, suggesting that the learning of a new skill involves a rewiring process of neural circuits. Since the extent of spine remodeling correlates with success of learning, this suggests a crucial role of synaptic structural plasticity in memory formation. In addition, changes in spine stability and strengthening occur rapidly and have been observed within hours after training.
Conversely, while enrichment and training are related to increases in spine formation and stability, long-term sensory deprivation
Sensory deprivation
Sensory deprivation or perceptual isolation is the deliberate reduction or removal of stimuli from one or more of the senses. Simple devices such as blindfolds or hoods and earmuffs can cut off sight and hearing respectively, while more complex devices can also cut off the sense of smell, touch,...
leads to a decrease in the rate of spine elimination and therefore impacts long-term neural circuitry. Upon restoring sensory experience after deprivation in adolescence, spine elimination is accelerated, suggesting that experience plays an important role in the net loss of spines during development. In addition, other sensory deprivation paradigms—such as whisker trimming—have been shown to increase the stability of new spines.
Research in neurological diseases and injuries shed further light on the nature and importance of spine turnover. After stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, a marked increase in structural plasticity occurs near the trauma site, and a five- to eightfold increase from control rates in spine turnover has been observed. Dendrites disintegrate and reassemble rapidly during ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
—as with stroke, survivors showed an increase in dendritic spine turnover. While a net loss of spines is observed in Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
and cases of mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, cocaine and amphetamine use have been linked to increases in dendritic branching and spine density in the prefrontal cortex
Prefrontal cortex
The prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
and the nucleus accumbens
Nucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
. Because significant changes in spine density occur in various brain diseases, this suggests a balanced state of spine dynamics in normal circumstances, which may be susceptible to disequilibrium under varying pathological conditions.
There is also some evidence for loss of dendritic spines as a consequence of aging. One study using mice has noted a correlation between age-related reductions in spine densities in the hippocampus that and age-dependent declines in hippocampal learning and memory.
Importance Contested
Despite experimental findings that suggest a role for dendritic spine dynamics in mediating learning and memory, the degree of structural plasticity’s importance remains debatable. For instance, studies estimate that only a small portion of spines formed during training actually contribute to lifelong learning. In addition, the formation of new spines may not significantly contribute to the connectivity of the brain, and spine formation may not bear as much of an influence on memory retention as other properties of structural plasticity, such as the increase in size of spine heads.Electrotonic properties
Electrotonic conductionElectrotonic potential
In physiology, electrotonus refers to the "passive" spread of charge inside a neuron. "Passive" means that voltage-dependent changes in membrane conductance do not contribute. Neurons and other excitable cells produce two types of electrical potential. The first is a non-propagated local potential...
refers to the passive conduction of current. Dendritic spines have a number of specific electrotonic properties. A dendritic spine has high input resistance
Electrical resistance
The electrical resistance of an electrical element is the opposition to the passage of an electric current through that element; the inverse quantity is electrical conductance, the ease at which an electric current passes. Electrical resistance shares some conceptual parallels with the mechanical...
, the resistance increases with smallness of headsize and narrowness of stemsize. The capacitance
Capacitance
In electromagnetism and electronics, capacitance is the ability of a capacitor to store energy in an electric field. Capacitance is also a measure of the amount of electric potential energy stored for a given electric potential. A common form of energy storage device is a parallel-plate capacitor...
of the membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s of spines is relatively small with the result that synaptic potentials can be relatively fast. The capacitance of the whole dendrite however becomes higher as the number of spines increases. Because there is an impedance mismatch
Impedance matching
In electronics, impedance matching is the practice of designing the input impedance of an electrical load to maximize the power transfer and/or minimize reflections from the load....
between the dendritic spine and the dendrite, it is necessary with active signal boosting. The impedance mismatch also causes the spine to follow the potential of the parent dendrite.
Modelling
Theoreticians have for decades hypothesized about the potential electrical function of spines, yet our inability to examine their electrical properties has until recently stopped theoretical work from progressing too far. Recent advances in imaging techniques along with increased use of two-photon glutamate uncaging have led to a wealth of new discoveries; we now suspect that there are voltage-dependent sodium, potassium, and calcium channels in the spine heads.Cable theory
Cable theory
Classical cable theory uses mathematical models to calculate the flow of electric current along passive neuronal fibers particularly dendrites that receive synaptic inputs at different sites and times...
provides the theoretical framework behind the most "simple" method for modelling the flow of electrical currents along passive neural fibres. Each spine can be treated as two compartments, one representing the neck, the other representing the spine head. The compartment representing the spine head alone should carry the active properties.
Baer and Rinzel's Continuum Model
To facilitate the analysis of interactions between many spines, Baer & Rinzel formulated a new cable theory for which the distribution of spines is treated as a continuum. In this representation, spine head voltage is the local spatial average of membrane potential in adjacent spines. The formulation maintains the feature that there is no direct electrical coupling between neighboring spines; voltage spread along dendrites is the only way for spines to interact.The Spike-Diffuse-Spike Model
The SDS model was intended as a computationally simple version of the full Baer and Rinzel model. It was designed to be analytically tractable and have as few free parameters as possible while retaining those of greatest significance, such as spine neck resistance. The model drops the continuum approximation and instead uses a passive dendrite coupled to excitable spines at discrete points. Membrane dynamics in the spines are modelled using integrate and fire processes. The spike events are modelled in a discrete fashion with the wave form conventionally represented as a rectangular function.Modelling spine calcium transients
Calcium transients in spines are a key trigger for synaptic plasticity. NMDA receptorNMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s, which have a high permeability for calcium, only conduct ions if the membrane potential is suffiently depolarized. The amount of calcium entering a spine during synaptic activity therefore depends on the depolarization of the spine head. Evidence from calcium imaging experiments (two-photon microscopy) and from compartmental modelling indicates that spines with high resistance necks experience larger calcium transients during synaptic activity.
Development
Dendritic spines are believed to develop from filopodiaFilopodia
Filopodia are slender cytoplasmic projections that extend beyond the leading edge of lamellipodia in migrating cells. They contain actin filaments cross-linked into bundles by actin-binding proteins, e.g. fascin and fimbrin. Filopodia form focal adhesions with the substratum, linking it to the...
. During synaptogenesis
Synaptogenesis
Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...
, dendrites rapidly sprout and retract filopodia, small membrane organelle-lacking membranous protrusions. During the first week of birth, the brain is predominated by filopodia, which eventually develop synapses. However, after this first week, filopodia are replaced by spiny dendrites but also small, stubby spines that protrude from spiny dendrites. In the development of certain filopodia into spines, filopodia recruit presynaptic contact to the dendrite, which encourages the production of spines to handle specialized postsynaptic contact with the presynaptic protrusions.
Spines, however, require maturation after formation. Immature spines have impaired signaling capabilities, and typically lack "heads" (or have very small heads), only necks, while matured spines maintain both heads and necks.
Pathology
Cognitive disorders such as ADHD, autismAutism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, and fragile X syndrome
Fragile X syndrome
Fragile X syndrome , Martin–Bell syndrome, or Escalante's syndrome , is a genetic syndrome that is the most commonly known single-gene cause of autism and the most common inherited cause of intellectual disability...
, may be resultant from abnormalities in dendritic spines, especially the number of spines and their maturity. The ratio of matured to immature spines is important in their signaling, as immature spines have impaired synaptic signaling. Fragile X syndrome is characterized by an overabundance of immature spines that have multiple filopodia in cortical dendrites.